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Background Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. Methods We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21–28), and late follow-up (LFU; Days 35–42). Results A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P  = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Conclusions Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered. [ABSTRACT FROM AUTHOR]

The primary factor behind Enterobacteriaceae members' resistance to β-lactam antibiotics is extended spectrum β-lactamases. Infections of the urinary tract are most frequently caused by Escherichia coli, a member of the Enterobacteriaceae family (UTIs). About 80% of isolates that lead to urinary tract infections are E. coli. For the treatment of urinary tract infections (UTIs), beta-lactam antibiotics such as cephalosporins and penicillins are the most widely prescribed and safest antimicrobial medicines. Our goals were to look at the prevalence of E. coli that produces ESBL and identify drugs that work well against isolates of E. coli that produce ESBL from urine samples. To study the treatment option for urinary tract infections caused by extended spectrum β-lactamase producing E. coli. In all, 312 E. coli isolates were obtained from urine samples throughout the August 2022-December 2023 study period. Testing for antimicrobial susceptibility was done according to the CLSI guidelines. The double disk diffusion test revealed the presence of ESBL production. In the present study, out of the 312 E. coli isolates, 71(22.7%) were phenotypically identified as ESBL producers and 241(77.3%) were non-ESBL. Among 71 ESBL producing E. coli strains, 51 (71.8%) belong to In-patients and 20 (28.2%) belong to Out-patients gave statistically significant results. All ESBL (100%) were sensitive to Nitrofurantoin. In conclusion, our study is the first in-depth investigation of antibiotic resistance from a tertiary care hospital in Lucknow and it demonstrates a low incidence of ESBL among E. coli isolates. This may facilitate the implementation of control measures for hospital- and community-based illnesses caused by the emergence of antibiotic resistance. [ABSTRACT FROM AUTHOR]

In the ongoing battle against antibiotic-resistant bacteria, New Delhi metallo-β-lactamase-1 (NDM-1) has emerged as a significant therapeutic challenge due to its ability to confer resistance to a broad range of β-lactam antibiotics. This study presents a pharmacophore-based virtual screening, docking, and molecular dynamics simulation approach for the identification of potential inhibitors targeting NDM-1, a critical enzyme associated with antibiotic resistance. Through the generation of a pharmacophore model and subsequent virtual screening of compound libraries, candidate molecules (ZINC29142850 (Z1), ZINC78607001 (Z2), and ZINC94303138 (Z3)) were prioritized based on their similarity to known NDM-1 binder (hydrolyzed oxacillin (0WO)). Molecular docking studies further elucidated the binding modes and affinities of the selected compounds towards the active site of NDM-1. These compounds demonstrated superior binding affinities to the enzyme compared to a control compound (−7.30 kcal/mol), with binding scores of −7.13, −7.92, and −8.10 kcal/mol, respectively. Binding interactions within NDM-1's active site showed significant interactions with critical residues such as His250, Asn220, and Trp93 for these compounds. Subsequent molecular dynamics simulations were conducted to assess the stability of the ligand–enzyme complexes, showing low root mean square deviation (RMSD) values between 0.5 and 0.7 nm for Z1, Z2, which indicate high stability. Z2's compactness in principal component analysis (PCA) suggests that it can stabilize particular protein conformations more efficiently. Z2 displays a very cohesive landscape with a notable deep basin, suggesting a very persistent conformational state induced by the ligand, indicating robust binding and perhaps efficient inhibition. Z2 demonstrates the highest binding affinity among the examined compounds with a binding free energy of −25.68 kcal/mol, suggesting that it could offer effective inhibition of NDM-1. This study highlights the efficacy of computational tools in identifying novel antimicrobial agents against resistant bacteria, accelerating drug discovery processes. [ABSTRACT FROM AUTHOR]

Prescribing antibiotics is a regular part of daily dental practice. Antibiotics have a significant but a limited role in general dental practice due to the threat of emergence of antimicrobial resistance (AMR). As such, the aim of this study was to assess prescribing trends in dental antibiotics use from 2014–2023 in Croatia. Data on antibiotic prescribing practices for this study were provided by the Croatian Health Insurance Fund. The analysis included the number of prescriptions, packages, cost, and the World Health Organization's defined daily dose per 1000 inhabitants (DID) per day as an objective utilization for comparison. Over the 10-year period, dentists in Croatia prescribed an annual average of 357,875 antibiotic prescriptions, representing an annual average of 78.7% of all dental prescriptions. The most commonly prescribed antibiotic was the combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid, which made up 58.54% of antibiotics and 46.1% of all dental prescriptions. This was followed by amoxicillin (12.61%), clindamycin (12.58%), and metronidazole (9.96%). The trend showed two discontinuations, the first for the pandemic years, and the second caused by disruption in amoxicillin production. The rise in the use of broad-spectrum antibiotics needs to be addressed and regulated to ensure patients and dentists understand that antibiotics are not a substitute for dental treatment. Dentists should always begin treatment with narrow-spectrum antibiotics regardless of possible exceptional circumstances. [ABSTRACT FROM AUTHOR]

Introduction: Novel beta-lactam/beta-lactamase inhibitor (BIBLI) combinations are commercially available and have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profiles and resistance mechanism identification are necessary to monitor the evolution of resistance within these agents. Objective: The purpose of this study was to evaluate the susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolated from patients with bloodstream infections who underwent screening for a randomized clinical trial in Brazil. Methods: Minimum inhibitory concentrations (MICs) were determined for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam using the gradient diffusion strip method. Carbapenemase genes were detected by multiplex real-time polymerase chain reaction. Klebsiella pneumoniae carbapenemase (KPC)-producing isolates showing resistance to any BLBLI and New Delhi Metallo-beta-lactamase (NDM)-producing isolates with susceptibility to any BLBLI isolates were further submitted for whole-genome sequencing. Results: From a total of 69 CRKP isolates, 39 were positive for blaKPC, 19 for blaNDM and 11 for blaKPC and blaNDM. KPC-producing isolates demonstrated susceptibility rates above 94 % for all BLBLIs. Two isolates with resistance to meropenem/vaborbactam demonstrated a Gly and Asp duplication at the porin OmpK36 as well as a truncated OmpK35. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0 %, 9.1–21.1 % and 9.1–26.3 %, respectively. Five NDM-producing isolates that presented susceptibility to BLBLIs also had porin alterations Conclusions: This study showed that, although high susceptibility rates to BLBLIs were found, KPC-2 isolates were able to demonstrate resistance probably as a result of porin mutations. Additionally, NDM-1 isolates showed susceptibility to BLBLIs in vitro.

Infections due to Haemophilus influnezae require prompt treatment using beta-lactam antibiotics. We used a collection of 81 isolates obtained between 1940 and 2001 from several countries. Whole genome sequencing showed the high heterogeneity of these isolates but allowed us to track the acquisition of beta-lactamase, which was first detected in 1980. Modifications of the ftsI gene encoding the penicillin-binding protein 3, PBP3, also involved in resistance to beta-lactams, appeared in 1991. These modifications (G490E, A502V, R517H, and N526K) were associated with resistance to amoxicillin that was not relieved by a beta-lactamase inhibitor (clavulanic acid), but the isolates retained susceptibility to third-generation cephalosporins (3GC). The modeling of the PBP3 structure suggested that these modifications may reduce the accessibility to the PBP3 active site. Other modifications appeared in 1998 and were associated with resistance to 3GC (S357N, M377I, S385T, and L389F). Modeling of the PBP3 structure suggested that they lie near the S379xN motif of the active site of PBP3. Overall resistance to amoxicillin was detected among 25 isolates (30.8%) of this collection. Resistance to sulfonamides was predicted by a genomic approach from the sequences of the folP gene (encoding the dihydropteroate synthase) due to difficulties in interpreting phenotypic anti-microbial testing and found in 13 isolates (16.0%). Our data suggest a slower spread of resistance to sulfonamides, which may be used for the treatment of H. influnezae infections. Genomic analysis may help in the prediction of antibiotic resistance, inform structure–function analysis, and guide the optimal use of antibiotics. [ABSTRACT FROM AUTHOR]

Carbapenems are the antibiotics of choice for treating multidrug-resistant bacterial infections. Metallo-β-lactamases (MBLs) are carbapenemases capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, this research assessed the distribution of two MBL genes and three β-lactamases and their associated phenotypic resistance in diarrheal and urinary-tract infections (UTIs) to guide future policies. Samples were collected through a cross-sectional study, and β-lactamase genes were detected via PCR. A total of 228 diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively. A total of 142 UTI pathogens were identified from 150 urine samples. Klebsiella spp. (39%) and Escherichia coli (24%) were the major pathogens isolated. Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively. Twenty-four diarrheal isolates carried blaNDM-1 or blaVIM genes. The overall MBL gene prevalence was 10.5%. Thirty-six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes. MBL genes were strongly associated with phenotypic carbapenem and other β-lactam antibiotic resistance. blaOXA imparted significantly higher phenotypic resistance to β-lactam antibiotics. Active surveillance and stewardship programs are urgently needed to reduce carbapenem resistance in Bangladesh. [ABSTRACT FROM AUTHOR]

Background: A parotid abscess (PA) is a complication of an acute bacterial parotitis with a potentially life-threatening course. To date, data on the diagnosis and therapy of PA is sparse and mostly consists of case reports or case series. Therefore, this study aimed at comprehensively analyzing the microbiological spectrum and the therapeutic management in a bi-institutional setting. Methods: A retrospective clinical chart review was performed to identify all patients surgically treated for PA at two tertiary care centers in Germany. Data on demographics, clinical management and microbiological data including species identification, pathogenicity, type of antibiotic therapy, adjustment of antibiotics, antibiotic sensitivity testing, and smear test results were extracted. Intervention-related variables and etiology were analyzed for their statistical association with outcome variables. Results: Overall, 85 patients were included. Most patients (92.9%) underwent surgical incision. Around half of the patients (45.9%) were treated under local anesthesia. No facial nerve palsy was observed. The most frequently detected pathogens were Streptococci (n = 23), followed by Staphylococcus aureus (n = 6) including one case of methicillin-resistant Staphylococcus aureus. Most patients (68.2%) received an aminopenicillin ± beta-lactamase inhibitor as empiric antibiotic therapy. In 6 cases the antibiotic therapy was modified after receiving the antibiogram. Four patients (5.2%) presented with recurrent PA. Etiology was idiopathic (42.4%), followed by tumorous (12.9%), obstructive, and immunosuppressive (each 11.8%). Patients with a dental focus (p = 0.007) had a longer duration of hospitalization. Conclusion: The results show that the surgical therapy of PA under local anesthesia is safe. A dental examination should routinely be performed to rule out a dental focus. Obtaining a microbiological specimen in order to modify antibiotic therapy if necessary and a histopathological specimen to rule out a tumorous etiology is obligate. [ABSTRACT FROM AUTHOR]

AbstractBovine mastitis is a mammary gland inflammation that can occur due to infectious pathogens, Staphylococcus aureus and Escherichia coli, which are, respectively, the most prevalent Gram-positive and Gram-negative bacteria associated with this disease. Currently, antibiotic treatment has become more complicated due to the presence of resistant pathogens. This review, therefore, aims to identify the most common resistance genes reported for these strains in the last four years. During the review, it was noted that blaZ, blaSHV, blaTEM, and blaampC are the most reported genes for S. aureus and E. coli, associated with drug inactivation, mainly β-lactamases. They are characterized by generating bacterial resistance to β-lactam antibiotics, the most common treatment in animal and human bacterial treatments (penicillins and cephalosporins, among others). Genes associated with efflux systems were also present in the two strains and included norA, tetA, tetC, and tetK, which generate resistance to macrolide and tetracycline antibiotics. Additionally, the effects of spreading resistance between animals and humans through direct contact (such as consumption of contaminated milk) or indirect contact (through environmental contamination) has been deeply discussed, emphasizing the importance of having adequate sanitation and antibiotic control and administration protocols. [ABSTRACT FROM AUTHOR]

Robinsoniella peoriensis is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, R. peoriensis is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of Robinsoniella, describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by Robinsoniella. The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was R. peoriensis, and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections' clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective. [ABSTRACT FROM AUTHOR]

Background: Unused pharmaceuticals are currently a public health problem. This study aimed to identify unused pharmaceuticals, research practices about the disposal methods, classify the medicines according to Anatomical Therapeutic Chemical codes (ATC) and, to determine the number of unused medicines. Methods: The study was designed as a cross-sectional study. Data were collected between April and August 2023 in Burdur-Türkiye by non-probability sampling technique (convenience method). Pharmaceuticals were classified according to ATC. Statistical Package for Social Science SPSS (V.24) package program was used for data analysis. Results: A total of 1120 people, 1005 in the first sample group and 115 in the second sample group, participated in the study. Findings of first sample group: A total of 4097 boxes of unused pharmaceuticals (4.7 ± 4.3 boxes/per capita) were detected. It was found that pharmaceuticals were stored in areas such as kitchens (59.1%) and refrigerators (38.6%), the reason for keeping them was reuse (41%), and the disposal practice was household garbage (81%). Paracetamol (648 boxes), Other cold preparation (303 boxes), Dexketoprofen (239 boxes), Diclofenac (218 boxes), Amoxicillin and beta-lactamase inhibitor (190 boxes) were found to be the most frequently unused pharmaceuticals. Using the unused medicines at home without consulting a physician was 94.1% (self-medication). Findings of second sample group: Of the 6189 dosage forms in 265 boxes pharmaceutical, 3132(50.6%) dosage forms were used and 3057(49.4%) were found to be unused. Conclusion: There is a significant amount and number of unused medicines in households, and self-medication is common. Medicines are not properly disposed of and some of them expire. Public information is needed. A "drug take-back system" for unused medicines can be useful in solving this problem. [ABSTRACT FROM AUTHOR]

Introduction: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. Methods: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. Results: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from −0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. Discussion/Conclusion: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broadspectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE). METHODS: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab1r). Resolution (or 2 grade reduction) ofHE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-onchronic liver failure was performed. RESULTS: Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32--70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8--63) in ab 1 r arm achieved the primary objective (P 5 0.84).Time to achieve the primary objective (3.6561.82days and4.1162.01days;P50.27) and in-hospitalmortalitywere similar amongboth groups (62%vs50%;P50.13). Seven percent and13%inthe aband ab1r groupsdeveloped nosocomial infections (P5 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower inhospital mortality (hazard ratio: 0.39 [95% CI, 0.2--0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6--1.63]) because of reduced nosocomial infections. DISCUSSION: Reversal of overt HE in those on ab was comparable with those on ab 1 r. [ABSTRACT FROM AUTHOR]

Objective: FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an in vitro infection model. Methods: By simulating human concentration-time profiles in the in vitro model, meropenem combined with FL058 when administered 1 g/0.5 g, 1 g/1 g, 2 g/1 g, and 2 g/2 g q8h by 3-h infusion achieved approximately 2- and 4-log10 kill to KPC/OXA-producing Klebsiella pneumoniae and Escherichia coli; the combination therapy could not inhibit NDM-producing K. pneumoniae but could maintain NDM-producing E. coli around a baseline. Results: The PK/PD indexes that best described the bacterial killing from baseline in log10 CFU/mL at 24 h were the percent time of free drug above the minimal inhibitory concentration (MIC) (%fT > MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT > 1 mg/L) for FL058. The targets for achieving a static effect and the 1- and 2-log10 kill were 74, 83, and 99 for %fT > MIC of meropenem and 40, 48, and 64 for %fT > 1 mg/L of FL058, respectively. The PK/PD index of %fT > 1 mg/L can provide a basis for evaluating clinical dosing regimens for FL058 combined with meropenem. Conclusion: FL058 combined with meropenem might be a potential treatment for KPC- and/or OXA-48-producing Enterobacterales infection. [ABSTRACT FROM AUTHOR]

Background: Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin. Methods: A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated. Results: The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin. Conclusions: The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates. [ABSTRACT FROM AUTHOR]

Aim This study aimed to compare and characterize the resistance profile and the presence of extended-spectrum beta-lactamase (ESBL) related genes in Escherichia coli isolated from healthy finishing pigs fed with or without antibiotics in their diets. Methods and results A total of 27 ceftiofur-resistant E. coli isolates were obtained from 96 healthy pigs. The antibiotic resistance profile was tested, and all 27 isolates were classified as multidrug-resistant (MDR). A high proportion of isolates were resistant to cephalosporins, ampicillin, ciprofloxacin, and tetracyclines. The ESBL production was observed in 85% of isolates by double-disc synergy test. The MDR- E. coli isolates harbored ESBL genes, such as bla TEM, bla CTX-M-1, bla CTX-M-2, and bla CTX-M-8,25. In addition, other antibiotics resistance genes (ARGs) were also detected, such as sul2, ant(3″)-I, tetA , and mcr-1. The mobilization of the bla CTX-M gene was confirmed for nine E. coli isolates by conjugation assays. The presence of bla CTX-M on mobile genetic elements in these isolates was demonstrated by Southern blot hybridization, and the resistance to cephalosporins was confirmed in the transconjugants. Our results indicate the prevalence of CTX-M-producing E. coli strains harboring mobile genetic elements in the normal microbiota of healthy pigs. Conclusions These findings highlight the significance of ESBL genes as a global health concern in livestock and the potential spread of antimicrobial resistance to other members of the gastrointestinal tract microbiota. [ABSTRACT FROM AUTHOR]

Background: Multi-Drug-ResistantKlebsiella pneumoniae (MDR K. pneumoniae) is considered as an important opportunistic pathogen, which causes life threatening infections. K. pneumoniae is known to causes life-threatening infections. Objective: The objective of this study is to detect some β-lactamase genes in Klebsiella pneumoniae. Methods: Thirty-five K. pneumoniae isolates were obtained from some hospitals in Baghdad City between October 2022 and February 2023. The identification of K. pneumoniae isolates was done phenotypically by the automated VITEK II system and genotypically by amplification of the rpob gene. The antibiotic susceptibility and detection of some β-lactamase genes were tested for all isolates. Results: The results showed that the K. pneumoniae isolates were resistant to most antibiotics used. A high percentage of K. pneumoniae isolates were resistant to cefixime, cefpodoxime, norfloxacin and doxycycline as 100% followed by ceftriaxone, ceftazidime, ticarcillin/clavulanate, ticarcillin, ceftazidime, tobramycin, and moxifloxacin (97.2%, 91.7%, 91.7%, 94.4%, 94.4%, and 94.4%, respectively). Furthermore, approximately 94.4% of the isolates were MDR. In addition, the molecular methods only detected the blaNDM and blaTEM genes as 33.3% and 75.6% of in the K. pneumoniae isolates, respectively, while the blaVIM, blaCTX−M, and blaKPC genes were not observed in K. pneumoniae isolates. Conclusions: β-lactam antibiotics, including carbapenems, are widely used to treat bacterial infections; however, an increase in antibiotic resistance due to β-lactamases limits the effectiveness of these antibiotics. Therefore, alternative treatment methods are required to control these resistant isolates. [ABSTRACT FROM AUTHOR]

Background: The convergence of hypervirulence and carbapenem resistance in the bacterial pathogen Klebsiella pneumoniae represents a critical global health concern. Hypervirulent K. pneumoniae (hvKp) strains, frequently from sequence type 23 (ST23) and having a K1 capsule, have been associated with severe community-acquired invasive infections. Although hvKp were initially restricted to Southeast Asia and primarily antibiotic-sensitive, carbapenem-resistant hvKp infections are reported worldwide. Here, within the carbapenemase production Enterobacterales surveillance system headed by the Chilean Public Health Institute, we describe the isolation in Chile of a high-risk ST23 dual-carbapenemase-producing hvKp strain, which carbapenemase genes are encoded in a single conjugative plasmid. Results: Phenotypic and molecular tests of this strain revealed an extensive resistance to at least 15 antibiotic classes and the production of KPC-2 and VIM-1 carbapenemases. Unexpectedly, this isolate lacked hypermucoviscosity, challenging this commonly used hvKp identification criteria. Complete genome sequencing and analysis confirmed the K1 capsular type, the KpVP-1 virulence plasmid, and the GIE492 and ICEKp10 genomic islands carrying virulence factors strongly associated with hvKp. Although this isolate belonged to the globally disseminated hvKp clonal group CG23-I, it is unique, as it formed a clade apart from a previously reported Chilean ST23 hvKp isolate and acquired an IncN KPC-2 plasmid highly disseminated in South America (absent in other hvKp genomes), but now including a class-I integron carrying blaVIM−1 and other resistance genes. Notably, this isolate was able to conjugate the double carbapenemase plasmid to an E. coli recipient, conferring resistance to 1st -5th generation cephalosporins (including combinations with beta-lactamase inhibitors), penicillins, monobactams, and carbapenems. Conclusions: We reported the isolation in Chile of high-risk carbapenem-resistant hvKp carrying a highly transmissible conjugative plasmid encoding KPC-2 and VIM-1 carbapenemases, conferring resistance to most beta-lactams. Furthermore, the lack of hypermucoviscosity argues against this trait as a reliable hvKp marker. These findings highlight the rapid evolution towards multi-drug resistance of hvKp in Chile and globally, as well as the importance of conjugative plasmids and other mobile genetic elements in this convergence. In this regard, genomic approaches provide valuable support to monitor and obtain essential information on these priority pathogens and mobile elements. [ABSTRACT FROM AUTHOR]

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account. [ABSTRACT FROM AUTHOR]

Acinetobacter is an important nosocomial pathogen causing health care associated infections. It is highly antibiotic resistant gram-negative bacilli. The study was done to determine the prevalence of Acinetobacter species isolated from various clinical samples with their antibiotic susceptibility pattern. To determine the antimicrobial susceptibility pattern of the isolated Acinetobacter species and also the multidrug resistant mechanisms by phenotypic characterization. The retrospective study was carried out in patients diagnosed with Acinetobacter infection in the Microbiology Department, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Deemed To Be University, Karad, a tertiary care hospital, including the clinical departments, during the period of two years from November 2020 till November 2022. Organism identification, biochemical test, antibiotic resistance pattern and phenotypic tests such as ESBL, MBL and Carbapenemase production were performed as per the Clinical and Laboratory Standards Institute (CLSI). The Modified Hodge test (MHT) was performed for Carbapenemase production detection in Acinetobacter species. A total of 150 Acinetobacter species were isolated from clinical samples. Acinetobacter baumannii was the most prevalent species 138 (92%), followed by Acinetobacter lwoffii 10 (7%) and Acinetobacter hemolyticus 2 (1%). The isolates showed highest resistance to Ampicillin 130 (87%) and sensitive to Colistin 113 (75.3%). Most of the isolates of of Acinetobacter baumannii showed maximum ESBL 21(14%) and MBL 75 (93%) production. Modified Hodge test showed positive results in Acinetobacter baumannii, only 11 (7%). The study showed that Acinetobacter baumannii was the most prevalent species showing drug resistance by phenotypic detection methods. At present Acinetobacter is a frequent pathogen in hospital acquired infections in critically ill patients admitted to ICU. The isolates of Acinetobacter species in our study showed resistant to most commonly used antibiotics. The study showed that ESBL production in Acinetobacter was 22 (15%) and MBL 80 (53%). Most Acinetobacter isolates were Multi Drug Resistant (MDR). MDR Acinetobacter is widely increasing due to inappropriate use of antibiotics in healthcare hospital. In our study, detection of carbapenemase by Modified Hodge test was positive in 11 (7%) isolates. [ABSTRACT FROM AUTHOR]

AmpC beta-lactamases cause resistance to third-generation cephalosporins, including beta-lactamase inhibitors. In Escherichia coli from the German food production chain, the majority of AmpC beta-lactamase activity can be attributed to plasmid-mediated CMY-2 or overproduction of chromosomal AmpC beta-lactamase, but occasionally other enzymes like DHA-1 are involved. This study investigated the prevalence of the AmpC beta-lactamase DHA-1 in ESBL/AmpC-producing E. coli (n = 4706) collected between 2016 and 2021 as part of a German antimicrobial resistance monitoring program along the food chain. Eight isolates (prevalence < 0.2%) were detected and further characterized by PFGE, transformation and conjugation experiments as well as short-read and long-read sequencing. All eight strains harbored blaDHA-1 together with qnrB4, sul1 and mph(A) resistance genes on an IS26 composite transposon on self-transferable IncFII or IncFIA/FIB/II plasmids. During laboratory experiments, activation of the translocatable unit of IS26-bound structures was observed. This was shown by the variability of plasmid sizes in original isolates, transconjugants or transferred plasmids, and correspondingly, duplications of resistance fragments were found in long-read sequencing. This activation could be artificial due to laboratory handling or naturally occurring. Nevertheless, DHA-1 is a rare AmpC beta-lactamase in livestock and food in Germany, and its dissemination will be monitored in the future. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a global health issue that affects humans, animals, and agriculture. This study assessed the prevalence and antimicrobial susceptibility of extended-spectrum betalactamase-producing Escherichia coli (ESBL-EC) in poultry and hand swabs of meat handlers working in a dressing plant in the Philippines. Fourteen (14) hand swabs from poultry handlers and 89 poultry cecal samples were collected and screened for ESBL production using MacConkey agar supplemented with cefotaxime and eosin methylene blue agar. Identification of E. coli through biochemical testing and antimicrobial susceptibility testing was then performed using the VITEK 2 System. Results showed that 7.14% (1/14) of the hand swabs and 23.60% (21/89) of the poultry cecal samples were positive for ESBL-EC. Identified isolates were further evaluated for their antimicrobial susceptibility using 33 antibiotics from various groups. Results showed 100% (22/22) resistance to the following antimicrobial drugs: ampicillin, ticarcillin, cefalotin, cefuroxime, cefuroxime axetil, cefixime, cefotaxime, nalidixic acid, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, tetracycline, trimethoprim, and trimethoprim/sulfamethoxazole. Resistance of select ESBL-EC isolates against other drugs under the beta-lactam, tetracycline, chloramphenicol, and aminoglycoside groups were also observed. Antimicrobial-resistant bacteria may be found in both human and animal sources, which highlights the need for ensuring safety practices to prevent their spread in the community. Gene sequencing and phylogenetic analysis may be used to further evaluate this relationship. Continuous surveillance and review of standards and protocols are also needed to monitor antimicrobial resistance, as underlined by the strategies of the One Health approach. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the possible role of wildlife in the Atlantic Forest and Caatinga biomes of Bahia, Brazil, as reservoirs of Salmonella. Very low frequencies (4/674 = 0.59%) of Salmonella infections and antibiotic resistance were observed. Thus, the findings of this study indicated that a wide variety of wildlife species do not carry Salmonella. This may be attributed to minimal human interference. Bacteria of potential public health concern were only detected in areas with high human interaction; therefore, we propose that Salmonella may be a good indicator of degradation in wildlife environments. Salmonella spp. are known to persist in the environment. Wild animals are believed to act as important reservoirs, with antimicrobial resistance frequently occurring in the environment. However, little is known about the role of the wildlife in Bahia as a reservoir for Salmonella in Brazil. This study aimed to isolate and characterize Salmonella spp. from wildlife in the Atlantic Forest and Caatinga biomes considering indicators such as the animal species, degree of anthropization, sampling area, and feeding habits. Convenience wildlife sampling and characterization were conducted, followed by microbiological and molecular identification of Salmonella isolates, serotyping, and antimicrobial susceptibility testing. A total of 674 fecal samples were collected from 12 municipalities during 2015–2021, and 4 were positive for the following Salmonella species: Salmonella enterica subspecies enterica serovar Agona (n = 1), Salmonella enterica subsp. enterica serogroup O:16 (n = 2), and Salmonella enterica subsp. enterica serovar Muenchen (n = 1). Antimicrobial susceptibility analysis revealed that one isolate was resistant to six antibiotics, including extended-spectrum penicillins and beta-lactamase inhibitors. These results indicated a low frequency of Salmonella spp. in the sampled forest fragments. The presence of Salmonella in wild animals increases the risk to public health and biodiversity and indicates that they can act as sentinels of environmental contamination or indicators of preservation. [ABSTRACT FROM AUTHOR]

A point prevalence survey (PPS) is used to collect data on antimicrobial prescribing and assess a set of quality indicators associated with antimicrobial use. This study aimed to describe patterns and quality indicators of antibiotic prescribing among government hospitals in Perak, Malaysia. Data was retrospectively reviewed data from a PPS conducted from 1st to 14th December 2021 in 5 specialist and 10 non-specialist hospitals. All hospitalised patients on the day of the survey formed the study population. Those who had received at least one active systemic antibiotic by 8.00 a.m. or surgical prophylaxis within 24 h of the survey day were eligible for PPS. Data on pattern and quality indicators of prescribing (documentation of indication, guideline compliance and appropriateness of surgical prophylaxis) were analysed with descriptive evaluation. Of 2,386 hospitalised patients, 40% were prescribed antibiotics, mainly from the 'Access' category (52.3%). Antibiotic prevalence was highest in the intensive care unit (ICU) (90.8%). The predominant antibiotic class was beta-lactam/ beta-lactamase inhibitor (32.6%), corresponding to community-acquired pneumonia (CAP) (19.8%) being the most common diagnosis. Intravenous administration was ordered in 79.4%, while empirical therapy constituted 84.5%. Documentation of indication within 24 h and guideline compliance were 88.2% and 69.8%, respectively. Inappropriate choice of antibiotics and improper dose/frequency were identified as important non-compliance issues. Of the surgical prophylaxis prescriptions, 35.6% were administered for more than 24 h. The findings have helped identify critical areas for antimicrobial stewardship interventions. Efforts are needed to reinforce compliance, documentation and improve surgical prophylaxis prescribing practices. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications. Methods: We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics. Results: A total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64–1.51 and 0.42; 95%CI: 0.16–1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06–31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58–17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74–17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09–14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69–7.44). 91.35% of antibiotics have an onset time of less than four weeks. Conclusions: There is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a major public health concern worldwide. This study aims to determine the prevalence of Enterobacterales producing beta-lactamase (TEM, SHV, OXA) or extended-spectrum beta-lactamases (ESBL), as well as plasmid-mediated resistance to quinolones (PMQR) (qnrA, qnrB, qnrS) in companion animals from the northeast region of Romania. A total of 124 faecal samples were collected aseptically from healthy dogs attending the veterinary practice for vaccination and cultivated on Brilliance ESBL medium (Oxoid, UK). The ESBL production testing was performed using the combination disc test. The identification of Enterobacterales strains was achieved using molecular identification and based on biochemical tests. Antimicrobial susceptibility testing was performed using the disk diffusion method. Identification of genes encoding for beta-lactamase enzymes and genes encoding plasmid-mediated resistance to quinolones was performed by PCR according to the protocols previously described. After ESBL screening, 31 (31/124; 25%) extended-spectrum cephalosporin (ESC)-resistant Enterobacterales were obtained, and 67.74% (21/31) of them were confirmed as ESBL-producers. Regarding the Enterobacterales species, 27 (27/31; 87.1%) were Escherichia coli and 4 (4/31; 12.9%) strains were Klebsiella pneumoniae. Among the ESBL-producing isolates, the blaCTX-M-1 gene group was predominant (58.82%), followed by the blaCTX-M-9 group (41.18%). The blaTEM, blaSHV and blaOXA gene groups were identified in 54.83%, 29.03% and 3.22% of the analysed strains, respectively. The prevalence of PMQR genes was 22.58% and consisted only of qnrS (19.35%) and qnrA (3.22%) genes. The prevalence of ESBL strains related to the total number of analysed samples was 16.93% (21/124). The findings show a significant prevalence of ESBLs and PMQR genes in Enterobacterales strains isolated from the faeces of healthy dogs, implying that pets may pose a risk of transmitting ESBL strains to other animals or owners. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is a major global threat to the efficacy of bacterial infection treatment. Resistance to beta-lactam antibiotics in bacteria is primarily caused by the production of extended-spectrum-lactamases, with the CTX-M variant, particularly CTX-M-15, being the most common. The need for an effective CTX-M-15 inhibitor is currently pressing. Methods: This study screened a library of natural compounds from the ZINC database against the CTX-M-15 protein using the PyRx 0.8 tool. The SwissADME web platform was used to predict the ADMET properties of the five most promising compounds. Result: The identified hits compounds, ZINC1857626342, ZINC403692, ZINC408773, ZINC57926, and ZINC790938591 exhibited strong binding with CTX-M-15. These compounds interacted with crucial catalytic site residues in the CTX-M-15 protein, particularly Ser70 and Ser130. Notably, the binding energies of these compounds were higher than those of the reference compound avibactam. Furthermore, they exhibited pharmacologically favorable characteristics. Conclusion: These compounds show promise as potential CTX-M-15 inhibitors to combat bacterial resistance. However, more experimental research is needed to optimize these compounds for their role as CTX-M-15 inhibitors. [ABSTRACT FROM AUTHOR]

This study assessed the efficacy and safety between broad spectrum penicillin (P2) with or without beta-lactamase inhibitors (P2+) versus first and second generation cephalosporins (C1&C2) in the prevention of post-cesarean infections. Relevant randomized controlled trials (RCTs) were searched in English and Chinese databases: nine RCTs were involved. Six trials compared P2+ vs C1&C2, no differences were found between interventions for endometritis, wound infection, urinary tract infection, febrile morbidity and maternal rashes. Four trials compared P2 vs C1&C2, no differences were found between interventions for endometritis, febrile morbidity, wound infection and urinary tract infection. Postoperative hospitalization was longer for women in P2 than C1&C2. Based on these results, P2/P2+ and C1&C2 may have similar efficacy on postoperative infections after cesarean section, there is no data on infant outcomes. PROSPERO Registration Number: CRD42022345721. [ABSTRACT FROM AUTHOR]

The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insufficiently studied, wherein the role of the inoculum effect (IE) in decreased efficacy is unclear. To address these issues, 5-day treatments with doripenem and doripenem/relebactam combination at different ratios of the agents were simulated in a hollow-fiber dynamic model against carbapenemase-producing K. pneumoniae at standard and high inocula. Minimal inhibitory concentrations (MICs) of doripenem alone and in the presence of relebactam at two inocula were determined. Combination MICs were tested using traditional (fixed relebactam concentration) and pharmacokinetic-based approach (fixed doripenem-to-relebactam concentration ratio equal to the therapeutic 24-h area under the concentration-time curve (AUC) ratio). In all experiments, resistant subpopulations were noted, but combined simulations reduced their numbers. With doripenem, the IE was apparent for both K. pneumoniae isolates in combined treatments for one strain. The pharmacokinetic-based approach to combination MIC estimation compared to traditional showed stronger correlation between DOSE/MIC and emergence of resistance. These results support (1) the constraint of relebactam combined with doripenem against the emergence of resistance and IE; (2) the applicability of a pharmacokinetic-based approach to estimate carbapenem MICs in the presence of an inhibitor to predict the IE and to describe the patterns of resistance occurrence. [ABSTRACT FROM AUTHOR]

Background: Denmark has a low level of antimicrobial resistance (AMR). Patients hospitalized with suspected infection often present with unspecific symptoms. This challenges the physician between using narrow-spectrum antibiotics in accordance with guidelines or broad-spectrum antibiotics to compensate for diagnostic uncertainty. The aim of this study was to investigate adherence to a restrictive antibiotic guideline for the most common infection in emergency departments (EDs), namely community-acquired pneumonia (CAP). Method: This multicenter descriptive cross-sectional study included adults admitted to Danish EDs with a suspected infection. Data were collected prospectively from medical records. Results: We included 954 patients in the analysis. The most prescribed antibiotics were penicillin with beta-lactamase inhibitor at 4 h (307 (32.2%)), 48 h (289 (30.3%)), and day 5 after admission (218 (22.9%)). The empirical antibiotic treatment guidelines for CAP were followed for 126 (31.3%) of the CAP patients. At 4 h, antibiotics were administered intravenously to 244 (60.7%) of the CAP patients. At day 5, 218 (54.4%) received oral antibiotics. Conclusion: Adherence to CAP guidelines was poor. In a country with a restrictive antibiotic policy, infections are commonly treated with broad-spectrum antibiotics against recommendations. [ABSTRACT FROM AUTHOR]

Increasing prevalence of infections caused by antimicrobial-resistant gram-negative bacteria represents a global health crisis, and while several novel therapies that target various aspects of antimicrobial resistance have been introduced in recent years, few are currently approved for children. Ceftazidime-avibactam is a novel β-lactam β-lactamase inhibitor combination approved for adults and children 3 months and older with complicated intra-abdominal infection, and complicated urinary tract infection or hospital-acquired ventilator-associated pneumonia (adults only in the United States) caused by susceptible gram-negative bacteria. Extensive population pharmacokinetic (PK) data sets for ceftazidime and avibactam obtained during the adult clinical development program were used to iteratively select, modify, and validate the approved adult dosage regimen (2,000-500 mg by 2-hour intravenous (IV) infusion every 8 hours (q8h), with adjustments for renal function). Following the completion of one phase I (NCT01893346) and two phase II ceftazidime-avibactam studies (NCT02475733 and NCT02497781) in children, adult PK data sets were updated with pediatric PK data. This paper describes the development of updated combined adult and pediatric population PK models and their application in characterizing the population PK of ceftazidime and avibactam in children, and in dose selection for further pediatric evaluation. The updated models supported the approval of ceftazidime-avibactam pediatric dosage regimens (all by 2-hour IV infusion) of 50-12.5 mg/kg (maximum 2,000-500 mg) q8h for those ≥6 months to 18 years old, and 40-10 mg/kg q8h for those ≥3 to 6 months old with creatinine clearance > 50 mL/min/1.73 m2 .

This article describes a rare case of a unique purpuric circular eruption in a patient with Capnocytophaga canimorsus bacteremia. Capnocytophaga canimorsus is a pathogen found in the oral cavity of dogs and can cause severe infections in immunocompromised individuals. The patient in this case was a 70-year-old woman with rheumatoid arthritis who developed a rash and fevers. The rash consisted of circular purpuric lesions that spread from her feet to her legs. The patient was treated with antibiotics and experienced complete resolution of her symptoms. The article emphasizes the importance of considering Capnocytophaga canimorsus infection in patients with diverse cutaneous eruptions and a history of dog bites. [Extracted from the article]

This study assessed the efficacy and safety between broad spectrum penicillin (P2) with or without beta-lactamase inhibitors (P2+) versus first and second generation cephalosporins (C1&C2) in the prevention of post-cesarean infections. Relevant randomized controlled trials (RCTs) were searched in English and Chinese databases: nine RCTs were involved. Six trials compared P2+ vs C1&C2, no differences were found between interventions for endometritis, wound infection, urinary tract infection, febrile morbidity and maternal rashes. Four trials compared P2 vs C1&C2, no differences were found between interventions for endometritis, febrile morbidity, wound infection and urinary tract infection. Postoperative hospitalization was longer for women in P2 than C1&C2. Based on these results, P2/P2+ and C1&C2 may have similar efficacy on postoperative infections after cesarean section, there is no data on infant outcomes. PROSPERO Registration Number: CRD42022345721.

The Beta-lactamase protein family is vital in countering Beta-lactam antibiotics, a widely used antimicrobial. To enhance our understanding of this family, we adopted a novel approach employing a multiplex network representation of its multiple sequence alignment. Each network layer, derived from the physiochemical properties of amino acids, unveils distinct insights into the intricate interactions among nodes, thereby enabling the identification of key motifs. Nodes with identical property signs tend to aggregate, providing evidence of the presence of consequential functional and evolutionary constraints shaping the Beta-lactamase family. We further investigate the distribution of evolutionary links across various layers. We observe that polarity manifests the highest number of unique links at lower thresholds, followed by hydrophobicity and polarizability, wherein hydrophobicity exerts dominance at higher thresholds. Further, the combinations of polarizability and volume, exhibit multiple simultaneous connections at all thresholds. The combination of hydrophobicity, polarizability, and volume uncovers shared links exclusive to these layers, implying substantial evolutionary impacts that may have functional or structural implications. By assessing the multi-degree of nodes, we unveil the hierarchical influence of properties at each position, identifying crucial properties responsible for the protein's functionality and providing valuable insights into potential targets for modulating enzymatic activity. [ABSTRACT FROM AUTHOR]

In recent years, new antimicrobials have been introduced in therapeutics, including new beta-lactam-beta-lactamase inhibitor combinations and cefiderocol in response to therapeutic needs in the face of increasing resistance. There are also different treatment guidelines for infections caused by these microorganisms that have been approved by different professional societies, including those of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Disease Society of America (IDSA) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). All of them are based on scientific evidence, but with differences in the weight of expert opinion in their recommendations. Both ESCMID and IDSA include recommendations for the treatment of extended-spectrum beta-lactamase-producing microorganisms. The IDSA is the only one including AmpC producers, all address the treatment of infections caused by carbapenem-resistant Enterobacterales and Acinetobacter baumannii and multidrug-resistant or difficult-to-treat Pseudomonas aeruginosa, and the IDSA and SEIMC include recommendations on the treatment of Stenotrophomonas maltophilia. Future guidelines should integrate new antimicrobials and new innovative management options not covered by current guidelines. [ABSTRACT FROM AUTHOR]

(1) Objectives: To describe the attainment of optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in orthotopic liver transplant (OLT) recipients treated with continuous infusion (CI) beta-lactams optimized using a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program during the early post-surgical period. (2) Methods: OLT recipients admitted to the post-transplant intensive care unit over the period of July 2021–September 2023, receiving empirical or targeted therapy with CI meropenem, piperacillin-tazobactam, meropenem-vaborbactam, or ceftazidime-avibactam optimized using a real-time TDM-guided ECPA program, were retrospectively retrieved. Steady-state beta-lactam (BL) and/or beta-lactamase inhibitor (BLI) plasma concentrations (Css) were measured, and the Css/MIC ratio was selected as the best PK/PD target for beta-lactam efficacy. The PK/PD target of meropenem was defined as being optimal when attaining a fCss/MIC ratio > 4. The joint PK/PD target of the BL/BLI combinations (namely piperacillin-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam) was defined as being optimal when the fCss/MIC ratio > 4 of the BL and the fCss/target concentration (CT) ratio > 1 of tazobactam or avibactam, or the fAUC/CT ratio > 24 of vaborbactam were simultaneously attained. Multivariate logistic regression analysis was performed for testing potential variables that were associated with a failure in attaining early (i.e., at first TDM assessment) optimal PK/PD targets. (3) Results: Overall, 77 critically ill OLT recipients (median age, 57 years; male, 63.6%; median MELD score at transplantation, 17 points) receiving a total of 100 beta-lactam treatment courses, were included. Beta-lactam therapy was targeted in 43% of cases. Beta-lactam dosing adjustments were provided in 76 out of 100 first TDM assessments (76.0%; 69.0% decreases and 7.0% increases), and overall, in 134 out of 245 total ECPAs (54.7%). Optimal PK/PD target was attained early in 88% of treatment courses, and throughout beta-lactam therapy in 89% of cases. Augmented renal clearance (ARC; OR 7.64; 95%CI 1.32–44.13) and MIC values above the EUCAST clinical breakpoint (OR 91.55; 95%CI 7.12–1177.12) emerged as independent predictors of failure in attaining early optimal beta-lactam PK/PD targets. (4) Conclusion: A real-time TDM-guided ECPA program allowed for the attainment of optimal beta-lactam PK/PD targets in approximately 90% of critically ill OLT recipients treated with CI beta-lactams during the early post-transplant period. OLT recipients having ARC or being affected by pathogens with MIC values above the EUCAST clinical breakpoint were at high risk for failure in attaining early optimal beta-lactam PK/PD targets. Larger prospective studies are warranted for confirming our findings. [ABSTRACT FROM AUTHOR]

Increasing antimicrobial resistance among multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), in particular metallo-β-lactamase (MBL)-positive strains, has led to limited treatment options in these isolates. This study evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparator antimicrobials against Enterobacterales isolates and key resistance phenotypes stratified by wards, infection sources and geographic regions as part of the ATLAS program between 2016 and 2020. Minimum inhibitory concentrations (MICs) were determined per Clinical and Laboratory Standards Institute (CLSI) guidelines. The susceptibility of antimicrobials were interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A tentative pharmacokinetic/pharmacodynamic breakpoint of 8 µg/mL was considered for ATM-AVI activity. ATM-AVI inhibited ≥99.2% of Enterobacterales isolates across wards and ≥99.7% isolates across infection sources globally and in all regions at ≤8 µg/mL. For resistance phenotypes, ATM-AVI demonstrated sustained activity across wards and infection sources by inhibiting ≥98.5% and ≥99.1% of multidrug-resistant (MDR) isolates, ≥98.6% and ≥99.1% of ESBL-positive isolates, ≥96.8% and ≥90.9% of carbapenem-resistant (CR) isolates, and ≥96.8% and ≥97.4% of MBL-positive isolates, respectively, at ≤8 µg/mL globally and across regions. Overall, our study demonstrated that ATM-AVI represents an important therapeutic option for infections caused by Enterobacterales, including key resistance phenotypes across different wards and infection sources. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Gram-negative bacterial infections are exponentially increasing, posing one of the most urgent global healthcare and economic threats. Due to the lack of new therapies, the World Health Organization classified these bacterial species as priority pathogens in 2017, known as ESKAPE pathogens. This classification emphasizes the need for urgent research and development of novel targeted therapies. The majority of these priority pathogens are Gram-negative species, which possess a structurally dynamic cell envelope enabling them to resist multiple antibiotics, thereby leading to increased mortality rates. Despite 6 years having passed since the WHO classification, the progress in generating new treatment ideas has not been sufficient, and antimicrobial resistance continues to escalate, acting as a global ticking time bomb. Numerous efforts and strategies have been employed to combat the rising levels of antibiotic resistance by targeting specific resistance mechanisms. These mechanisms include antibiotic inactivating/modifying enzymes, outer membrane porin remodelling, enhanced efflux pump action, and alteration of antibiotic target sites. Some strategies have demonstrated clinical promise, such as the utilization of beta-lactamase inhibitors as antibiotic adjuvants, as well as recent advancements in machine-based learning employing artificial intelligence to facilitate the production of novel narrow-spectrum antibiotics. However, further research into an enhanced understanding of the precise mechanisms by which antibiotic resistance occurs, specifically tailored to each bacterial species, could pave the way for exploring narrow-spectrum targeted therapies. This review aims to introduce the key features of Gram-negative bacteria and their current treatment approaches, summarizing the major antibiotic resistance mechanisms with a focus on Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Additionally, potential directions for alternative therapies will be discussed, along with their relative modes of action, providing a future perspective and insight into the discipline of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Global spread of multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages underscores the need for new therapeutic strategies. Here we show that many S. epidermidis isolates belonging to these lineages display cryptic susceptibility to penicillin/β-lactamase inhibitor combinations under in vitro conditions, despite carrying the methicillin resistance gene mecA. Using a mouse thigh model of S. epidermidis infection, we demonstrate that single-dose treatment with amoxicillin/clavulanic acid significantly reduces methicillin-resistant S. epidermidis loads without leading to detectable resistance development. On the other hand, we also show that methicillin-resistant S. epidermidis is capable of developing increased resistance to amoxicillin/clavulanic acid during long-term in vitro exposure to these drugs. These findings suggest that penicillin/β-lactamase inhibitor combinations could be a promising therapeutic candidate for treatment of a high proportion of methicillin-resistant S. epidermidis infections, although the in vivo risk of resistance development needs to be further addressed before they can be incorporated into clinical trials. Staphylococcus epidermidis can cause invasive infections that are difficult to treat due to multi-resistance to most clinically relevant drugs, including methicillin and other β-lactam antibiotics, vancomycin, and rifampicin. In this work, the authors use in vitro assays and a mouse infection model to explore cryptic susceptibility and development of resistance to penicillin/β-lactamase combinations. [ABSTRACT FROM AUTHOR]

Background: Achromobacter is a genus of gram-negative bacteria that can act as opportunistic pathogens. Recent studies have revealed that some species of Achromobacter show inherent resistance to β-lactams, but the resistance mechanisms of Achromobacter mucicolens have rarely been reported. Method: The bacterium was isolated using standard laboratory procedures. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs). Genome sequencing was performed using the PacBio RS II and Illumina HiSeq 2500 platforms, and the Comprehensive Antibiotic Resistance Database (CARD) was used to annotate the drug resistance genes. The localization of the novel β-lactamase AMZ-1 was determined, and its characteristics were determined via molecular cloning and enzyme kinetic analysis. The phylogenetic relationship and comparative genomic analysis of the resistance gene-related sequences were also analyzed. Result: Achromobacter mucicolens Y3, isolated from a goose on a farm in Wenzhou, showed resistance to multiple antibiotics, including penicillins and cephalosporins. BlaAMZ-1 showed resistance to amoxicillin, penicillin G, ampicillin, cephalothin and cefoxitin, and the resistance activity could be inhibited by β-lactamase inhibitors. Enzyme kinetic analysis results showed that AMZ-1 has hydrolytic activity against a wide range of substrates, including cephalothin, amoxicillin, penicillin G, and cefoxitin but not ampicillin. The hydrolytic activity of AMZ-1 was greatly inhibited by avibactam but much more weakly inhibited by tazobactam. Mobile genetic elements could not be found around the blaAMZ-1-like genes, which are conserved on the chromosomes of bacteria of the genus Achromobacter. Conclusion: In this study, a novel AmpC gene, blaAMZ-1, from the animal-origin bacterium A. mucicolens Y3 was identified and characterized. It conferred resistance to some penicillins and first- and second- generation cephalosporins. The identification of this novel resistance gene will be beneficial for the selection of effective antimicrobials to treat associated infections. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has become a serious threat to global public health and economic development. Rapid and accurate identification of a patient status for antimicrobial resistance (AMR) are urgently needed in clinical diagnosis. Here we describe the development of an assay method for activity fingerprinting of AMR β-lactamases using panels of 7 β-lactam antibiotics in 35 min. New Deli Metallo β-lactamase-1 (NDM-1) and penicillinase were demonstrated as two different classes of β-lactamases. The panel consisted of three classes of antibiotics, including: penicillins (penicillin G, piperacillin), cephalosporins (cefepime, ceftriaxone, cefazolin) and carbapenems (meropenem and imipenem). The assay employed a scheme combines the catalytic reaction of AMR β-lactamases on antibiotic substrates with a flow-injected thermometric biosensor that allows the direct detection of the heat generated from the enzymatic catalysis, and eliminates the need for custom substrates and multiple detection schemes. In order to differentiate classes of β-lactamases, characterization of the enzyme activity under different catalytic condition, such as, buffer composition, ion strength and pH were investigated. This assay could provide a tool for fast diagnosis of patient AMR status which makes possible for the future accurate treatment with selected antibiotics. [ABSTRACT FROM AUTHOR]

The growing prevalence of antibiotic-resistant bacteria is a worldwide public health apprehension, and Escherichia coli (E. coli) is one of the most commonly implicated bacterial species. Among E. coli isolates, extended-spectrum b-lactamase (ESBL)-producing strains have been identified as a key contributor to antibiotic resistance. Penicillin’s, cephalosporins, and monobactams are only a few of the b-lactam antibiotics that can be rendered inactive by ESBLs. This investigation’s goals were to determine the prevalence of ESBL-producing E. coli isolates found in clinical samples and to analyze the distribution of the blaTEM, blaSHV, and blaCTX-M genes among them. Additionally, we aimed to determine the antibiotic susceptibility patterns of these isolates to other antibiotics. Clinical isolates from urine, ear swab, and wound/pus swabs were collected from patients with suspected E. coli bacterial infections from different regions of north India viz., SKIMS-JVC medical college and NABL accredited Dr. Qadri’s Lab both from Srinagar Kashmir valley region and SMSR, SU from Greater Noida UP. Standard laboratory techniques were used to identify E. coli isolates, and the combined disc method and other phenotypic confirmation techniques were used to confirm ESBL formation. PCR amplification and sequencing were used to find the blaTEM, blaSHV, and blaCTX-M genes. The Kirby-Bauer disc diffusion method was used to test the antimicrobial susceptibility of various bacteria to different antibiotics. A total of 210 E. coli isolates were collected from different clinical samples and only 158 isolates showed positive results for ESBL by DDST and phenotypic confirmatory tests. Of these, 124 (78.48%) were ESBL-producing isolates. We found that blaTEM was the most prevalent gene (45.16%), followed by blaCTX-M (34.16%) and blaSHV (12.09%). Antimicrobial resistance profiles were assessed for each of the 120 isolates. Ampicillin and Cefepime were the most resistant drugs to ESBL-producing isolates, followed by Gentamicin, Ceftriaxone, and Cefixime. [ABSTRACT FROM AUTHOR]

Escherichia coli and Klebsiella pneumoniae are two important members of Enterobacteriaceae family. They are involved in sever community and hospital acquired infections such as urinary tract infections (UTIs), gastroenteritis, and pneumonia. Some of these diseases are associated with high mortality rates if not treated properly, so it is important to combat them with highly effective antibiotics. The most commonly used antimicrobial agents are beta-lactams such as penicillins, cephalosporins and other non-beta lactams such as aminoglycosides and quinolones. Extensive use of antimicrobials and disinfectants has promoted the rapid development of bacterial resistance. This bacterial resistance becomes a global health problem especially in developing countries. The increased rate of resistance towards different classes of antibiotics limits the treatment options for such infections. The antibacterial activity of some antimicrobial agents can be enhanced by the addition of new ß-lactamase inhibitors. Further in vivo investigation is needed to confirm their therapeutic efficacy against local isolates. [ABSTRACT FROM AUTHOR]

Ceftolozane‐tazobactam is a new β‐lactam/β‐lactamase inhibitor combination approved by the U.S. Food and Drug Administration in 2019 for the treatment of hospital‐acquired and ventilator‐associated pneumonia. The combination is a particularly potent inhibitor of penicillin‐binding proteins with higher affinity than other β‐lactam agents. Persons with cystic fibrosis (pwCF) often harbour resistant Gram‐negative bacteria in the airways and need antibiotics to prevent declining lung function. To test whether the introduction of ceftolozane‐tazobactam in the period 2015–2020 led to a bacterial population level increase in cephalosporin resistance in a Danish CF population. In vitro, activity of ceftolozane‐tazobactam was evaluated by susceptibility testing of clinical Pseudomonas aeruginosa isolated from pwCF from January 1, 2015, to June 1, 2020. Six thousand three hundred thirty two isolates collected from 210 adult pwCF were included. Thirty pwCF were treated with ceftolozane‐tazobactam at least once. Ceftolozane‐tazobactam exposure did not increase cephalosporin resistance on an individual or population level. However, resistance to ceftolozane‐tazobactam was recorded despite no prior exposure in four pwCF. Compared to ceftazidime, ceftolozane‐tazobactam had a better in vitro activity on P. aeruginosa. The percentage of non‐mucoid P. aeruginosa isolates susceptible to ceftolozane‐tazobactam were higher or equal to 5 other β‐lactams. Ceftolozane‐tazobactam expands the armamentaria against P. aeruginosa with acceptable levels for a selection of drug resistance. [ABSTRACT FROM AUTHOR]

Introduction: New beta-lactams, associated or not with beta-lactamase inhibitors (NBs/BIs), can respond to the spread of carbapenemase-producing enterobacteriales and nonfermenting carbapenem-resistant bacteria. The risk of emergence of resistance to these NBs/BIs makes guidelines necessary. The SRLF organized a consensus conference in December 2022. Methods: An ad hoc committee without any conflict of interest (CoI) with the subject identified the molecules (ceftolozane–tazobactam, ceftazidime–avibactam, imipenem–cilastatin–relebactam, meropenem–vaborbactam and cefiderocol); defined 6 generic questions; drew up a list of subquestions according to the population, intervention, comparison and outcomes (PICO) model; and reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Seven experts in the field proposed their own answers to the questions in a public session and answered questions from the jury (a panel of 10 critical-care physicians without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Due to the frequent lack of powerful studies that have used clinically important criteria of judgment, the recommendations were formulated as expert opinions as often as necessary. Results: The jury provided 17 statements answering 6 questions: (1) Is there a place in the ICU for the probabilistic use of new NBs/IBs active against Gram-negative bacteria? (2) In the context of documented infections with sensitivity to several of these molecules, are there pharmacokinetic, pharmacodynamic, ecological or medico-economic elements for prioritization? (3) What are the possible combinations with these molecules and in what context? (4) Should we integrate these new molecules into a carbapenem-sparing strategy? (5) What pharmacokinetic and pharmacodynamic data are available to optimize their mode of administration in critically ill patients? (6) What are the dosage adaptations in cases of renal insufficiency, hepatocellular insufficiency or obesity? Conclusion: These recommendations should optimize the use of NBs/BIs in ICU patients. [ABSTRACT FROM AUTHOR]

Estuarine and coastal waters are areas of potential concern for antimicrobial resistance because of the discharge of wastewater from sewage treatment plants and the run-off from urban and agricultural lands. Herein, we evaluate the antimicrobial resistance profiles in bacteria from dugongs (Dugong dugon), mammals that inhabit and feed in shallow coastal regions and, thus, are vulnerable to encountering water and sediment contaminated by human activities. Bacterial isolates were cultured from fresh faeces of four wild dugongs, as well as from one sediment sample from a dugong foraging ground in Queensland, Australia. Ten bacterial isolates underwent phenotypic antimicrobial susceptibility testing using disc diffusion and minimum inhibitory concentration testing, and genotypic resistance and virulence gene identification through whole genome sequencing. Four Staphylococcus warneri isolates and one Bacillus cereus isolate from dugong faeces were resistant to penicillin, with two S. warneri isolates also displaying resistance to trimethoprim. Four Escherichia coli isolates were all resistant to ampicillin. Resistance genes, including fosB, BcII, dfrC, blaZ, and mdfA, were identified in the isolates cultured from dugong faeces with two virulence genes (gad and lpfA) identified in all E. coli isolates. Lysinibacillus sphaericus cultured from the marine sediment and B. cereus from dugong faeces displayed phenotypic multidrug resistance (across categories of nonextended spectrum cephalosporins, penicillins and beta-lactamase inhibitors, and clindamycin; and for L. sphaericus, phosphonic acids). These results demonstrate the role that dugongs can play as a sentinel species for antimicrobial resistance in the coastal waters across their range, which includes both disturbed urban and rural regions. [ABSTRACT FROM AUTHOR]

Objective: The pulmonary rehabilitation program has beneficial effects on Coronavirus Disease 2019 (COVID-19). However, the response of each patient is not the same. The aim of this study is to compare the rehabilitation processes of severe and critical patients with COVID-19 infection and investigate the effects of sarcopenia and nutritional parameters on the rehabilitation course. Materials and Methods: Patients with COVID-19 infection who continued to use oxygen were enrolled and classified into severe or critical disease groups. The modified Medical Research Council scale, Borg Rating of Perceived Exertion scale, and Barthel Index were evaluated. A 6-minute walking test, hand grip strength (HGS), and chair stand test were performed. The thickness of the quadriceps muscle was measured by ultrasound to diagnose sarcopenia. Nutrition risk screening and daily protein and calorie intake were computed. Results: Twenty-two patients were included. The oxygen requirement at discharge was reduced compared to those admitted to the rehabilitation unit (p<0.001). Sarcopenia was present in 17 (77.3%) patients in all subjects, 12 (80%) patients in the severe disease group, and in 5 (71.4%) patients in the critical disease group. HGS and the Barthel Index were lower in the critical disease group (p=0.044 and p=0.037, respectively). The duration of rehabilitation was longer in the critical disease group (p=0.044). Daily protein and calorie consumption per kilogram were similar and low in both groups (both p>0.05). Conclusion: Sarcopenia and malnutrition were common in severe and critical COVID-19 disease patients. HGS was lower in critical disease patients, while muscle measurements were similar in both groups. [ABSTRACT FROM AUTHOR]

Objective: Cancer patients are a high-risk population for infections caused by various bacterial agents. Specifically, bloodstream infections (BSIs) can lead to severe complications and even mortality in cancer patients. This study aimed to identify the predominant bacterial species causing bacteremia and assess the prevalence of antibiotic resistance among cancer patients receiving treatment at our hospital. Materials and Methods: Retrospective analysis was conducted on data from cancer patients diagnosed between January 2020 and June. The microorganisms isolated from blood cultures of cancer patients were identified using the matrix-assisted laser desorption ionization (MALDI) Biotyper Microflex LT device. The antimicrobial susceptibility profiles of the bacteria were examined using the BD Phoenix 100. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) 22.0 program. Results: The study included a total of 158 bacterial isolates grown from blood cultures of 133 patients across different populations. Gram-positive bacteria were detected in 54.4% (86) of the isolates, while gram-negative bacteria were found in 40.5% (64) of the isolates. The extended spectrum beta-lactamase (ESBL) positivity rate was 41.2% (14/34) in Escherichia coli isolates and 25% (3/12) in Klebsiella pneumoniae isolates. Methicillin-resistant Staphylococcus aureus (MRSA) was identified in only one bacterial strain. Nine (26.5%) E. coli isolates and three (25%) K. pneumoniae isolates were determined to be multi-drug resistant (MDR). Conclusion: BSIs remain a significant health issue in cancer patients. Analyzing MDR isolates and resistance profiles through routine bacterial surveillance in cancer patients can provide guidance for antimicrobial therapy. Furthermore, regularly sharing the obtained data can enhance treatment success. [ABSTRACT FROM AUTHOR]

Zidebactam is a novel extended spectrum β-lactamase inhibitor (ESBLI). It's combination with cefepime (WCK 5222) is in phase III clinical studies. Five process impurities were found in zidebactam (1) drug substance using process development through reverse phase high performance liquid chromatography (HPLC) method. To give access to the reference standards for the impurity profile of the drug substance as well as the final product, these process impurities of compound 1, have been synthesized and characterized. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance continues to surmount increasing concern globally, and treatment of difficult‐to‐treat (DTR) Pseudomonas aeruginosa, carbapenem‐resistant (CR) Acinetobacter baumannii (CRAB), and CR Enterobacterales (CRE) remains a challenge for clinicians. Although previously rare, the incidence of multidrug‐resistant (MDR) and CR infections in pediatric patients has increased drastically in the last decade and is associated with increased morbidity and mortality. To combat this issue, 14 novel antibiotics, including three β‐lactam/novel β‐lactamase inhibitor combinations (βL‐βLIs) and two novel β‐lactams (βLs), have received approval from the United States Food and Drug Administration since 2010. Improving clinician understanding of the utility of these novel therapies is imperative to improve judicious decision‐making and prevent societal regression to a pre‐penicillin era. In this review, we summarize the pharmacokinetic/pharmacodynamic (PK/PD) properties, clinical efficacy and safety data, dosing considerations, and subsequent role in therapy for ceftazidime‐avibactam (CAZ‐AVI), meropenem‐vaborbactam (MER‐VAB), imipenem‐cilastatin‐relebactam (IMI‐REL), ceftolozane‐tazobactam (TOL‐TAZ), and cefiderocol in pediatric patients. [ABSTRACT FROM AUTHOR]