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A study published in the Journal of Antimicrobial Chemotherapy examined the development of resistance to ertapenem and meropenem among a type of bacteria called Enterobacterales. The researchers found that resistance to ertapenem occurred more easily than resistance to meropenem. They also observed that using ertapenem could potentially lead to resistance to meropenem. These findings emphasize the need to monitor and manage the use of carbapenem antibiotics to prevent resistance. Another study compared the effects of ertapenem and meropenem on carbapenem-resistant Enterobacteriaceae isolates. The study found that ertapenem isolates showed greater reductions in susceptibility compared to meropenem isolates. The authors suggest that this may support the use of meropenem over ertapenem in hospitals for treating these infections, but more research is needed. The study was funded internally and the authors have no conflicts of interest. [Extracted from the article]

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3–9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity. [ABSTRACT FROM AUTHOR]

Infections caused by antibiotic-resistant bacteria represent a serious threat to global public health. Recently, due to its increased resistance to carbapenems and β-lactams, Klebsiella pneumoniae has become one of the main causes of septicemia, pneumonia, and urinary tract infections. It is crucial to take immediate action and implement effective measures to prevent further spread of this issue. This study aims to report the prevalence and antibiotic resistance rates of K. pneumoniae strains isolated from clinical specimens from 2015 to 2020 at the University Hospital of Salerno, Italy. More than 3,800 isolates were collected from urine cultures, blood cultures, respiratory samples, and others. K. pneumoniae isolates showed broad resistance to penicillin and cephalosporins, and increased susceptibility to fosfomycin and gentamicin. Extended spectrum beta-lactamase (ESBL) isolates accounted for 20–22%. A high percentage of strains tested were resistant to carbapenems, with an average of 40% to meropenem and 44% to ertapenem. The production of ESBLs and resistance to carbapenems is one of the major public health problems. Constant monitoring of drug-resistant isolates is crucial for developing practical approaches in implementing antimicrobial therapy and reducing the spread of K. pneumoniae in nosocomial environments. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) is among the common bacterial infections in pediatric patients. These infections are more common in girls over one year old. This study aimed to investigate the bacterial distribution and drug resistance status in urine cultures of pediatric patients in our center. Materials and Methods: Urine culture results of patients who were presented to the outpatient clinics or were admitted to the Sivas Cumhuriyet University hospital between January 2017 and December 2022 were included in the study. The hospital automation system, patient files, and laboratory information management system were examined retrospectively. Statistical analysis was performed using the SPSS 22.0 software. A P-value of <0.05 was deemed significant. Results: Significant growth was observed in the urine cultures of a total of 1287 pediatric patients, 889 (69.1%) girls and 398 boys (30.9%). The patients included in the study were between the ages of 0-17, and children aged 1-6 (37.6%) were diagnosed with UTI more frequently than other ages. The most common UTI agent in the pediatric age group was Escherichia coli (56.6%). The first agent isolated in girls and boys is E.coli. Additionally, the prevalence of K. pneumoniae, P. mirabilis and K. oxytoca bacteria was higher in boys (p < 0.05). E. coli isolates showed minimal resistance to such as amikacin (0.6%), fosfomycin (1.0%), nitrofurantoin (1.4%), ertapenem (2.4%), imipenem (0.7%) and meropenem (0.9%). Conclusion: In this study, low resistance levels were detected for amikacin, fosfomycin, nitrofurantoin and carbapenem group antibiotics, which are important alternatives in the empirical treatment of UTI. On the other hand, due to the high resistance levels detected, it is thought that more caution should be exercised in the empirical use of amoxicillin-clavulanate, trimethoprimsulfamethoxazole and cefixime. If these antibiotics are to be preferred, waiting for the antibiogram results is an appropriate approach. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot osteomyelitis is a high-morbidity and debilitating complication of diabetic foot ulcers that contributes to significantly worse quality of life in the affected population and higher cost of healthcare services. One of the clinical presentations of diabetic foot osteomyelitis is the 'sausage' toe deformity, which affects the phalanges (local soft tissue infection and underlying bony changes). This deformity is highly suggestive of the presence of osteomyelitis. Unfortunately, during recent years, the emergence of antibiotic-resistant bacteria have created great difficulties in choosing appropriate empirical antibiotics for the treatment of diabetic foot infections. Multidrug-resistant pathogens have been strongly related to higher morbidity and mortality compared with infections caused by their antibiotic-susceptible counterparts. Case Report: We describe a case of a 74-year-old woman with long-standing insulin-treated type 2 diabetes, who experienced extended-spectrum beta-lactamase-producing Escherichia coli infection that caused diabetic foot osteomyelitis with 'sausage' deformity in her second right toe. She was successfully treated with surgical debridement combined with the administration of ertapenem in the outpatient setting, completing, in total, a 6-week course of antibiotic therapy. Conclusions: 'Sausage' toe deformity is one of the clinical presentations of diabetic foot osteomyelitis, and should be an alarming sign in everyday clinical practice. Ertapenem is an excellent option for the treatment of diabetic foot infections caused by extended-spectrum beta-lactamase E. coli in the outpatient setting. Early diagnosis and proper therapeutic approach are of great importance to reduce the risk of amputations, overall mortality, total cost, and the surge of antimicrobial resistance in the community. [ABSTRACT FROM AUTHOR]

Pregnant women are at high risk of urinary tract infections (UTIs). There is growing concern about the rise of Enterobacteriaceae that are resistant to drugs, including, more recently, those that produce carbapenemase. The study aimed to perform molecular detection and antibiograms of Enterobacteriaceae that produce carbapenemase in pregnant women with UTIs. Using clinical specimens taken from the general hospital in Qurrayat, Saudi Arabia, we identified 83 isolates of Enterobacteriaceae. Microscan WalkAway Plus and Phoenix automated analyzers were used to carry out bacterial isolation using standard microbiological procedures. DNA sequencing was employed to identify the carbapenemase bla genes, while phenotypic techniques and PCR were employed to characterize bacterial strains. The carbapenemase bla gene was detected among the 30 members of the Enterobacteriaceae. Of these 30, bla gene variants were found in 13 isolates (41%) blaOXA-23; 11 (35%) blaNDM-1; 10 (32%) blaNDM-5; 7 (22%) blaOXA-24; 4 (12%) blaVIM and 3 (9%) blaOXA-48. A statistically non-significant relationship between the blaNDM-1 and Klebsiella pneumoniae (p = 0.33) was seen, and the correlation between the blaNDM variants was not significantly associated with Pseudomonas aeruginosa (p = 0.5) and Escherichia coli (p = 0. 14). Antibiotic resistance was extremely common, as evidenced by the minimum inhibitory concentrations (MICs) in vitro of carbapenemase-producing Enterobacteriaceae against a number of antibiotic groups. These bacterial strains exhibited minimal resistance to amikacin (14; 46.6%) and were not resistant to two aminoglycosides, namely Ertapenem (30; 100%) and Meropenem (30; 100%). Our investigation shows that many Enterobacteriaceae that produce carbapenemases are a serious risk for pregnant women and others in the community. As a result, alternatives for therapy are limited to the aminoglycosides Ertapenem and Meropenem. [ABSTRACT FROM AUTHOR]

Objectives The aims of this study were: (i) to assess the ability of the meropenem screening breakpoint as part of the screening rapid antimicrobial susceptibility testing (sRAST) of EUCAST for the detection of OXA-48 carbapenemase-producing Klebsiella pneumoniae directly from positive blood cultures (BCs); and (ii) to evaluate the inclusion of ertapenem and temocillin discs into the sRAST to enhance the detection of OXA-48-producing isolates. Methods BC bottles were spiked with a total of 117 K. pneumoniae isolates, including 77 previously characterized OXA-48 producers and 40 non-OXA-48 producers. Disc diffusion assays were directly performed from positive BCs with meropenem (10 µg), ertapenem (10 µg) and temocillin (30 µg) discs, and inhibition zones were manually measured after 4, 6 and 8 h of incubation. The screening cut-off values of sRAST were applied to evaluate their capability in detecting OXA-48-producing isolates. Receiver operating characteristic curves were constructed to illustrate the performance efficacy of the disc diffusion assays to detect OXA-48 producers. Results The meropenem cut-off values of sRAST only detected 90.91% of the OXA-48-producing isolates after 6 and 8 h of incubation. With the proposed cut-off points for ertapenem [<19 mm (4/6 h) and <20 mm (8 h)] and temocillin [<10 mm (4 h) and <11 mm (6/8 h)], all OXA-48-positive isolates were detected without any false-positive results at any reading time. Conclusions In healthcare settings with a high prevalence of OXA-48 producers, the inclusion of ertapenem and temocillin discs in the sRAST procedure may improve the detection of OXA-48-producing K. pneumoniae isolates directly from positive BCs, providing reliable results after only a 4 h incubation period. [ABSTRACT FROM AUTHOR]

Introduction: The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a substantial severe global public health burden. Noncarbapenemase-producing CRKP (non-CP-CRKP) is increasingly recognized as the source of severe infections. Methodology: We analyzed the genotypic, and phenotypic profiles of non-CP-CRKP strains with the whole-genome sequences isolated between 2017 and 2019 and the clinical characterization of non-CP-CRKP infection. Results: A total of 91 CRKP strains were collected, of which 5 (5.49%) strains were non-CP-CRKP. Four strains were from male patients; three strains were isolated from the bile of patients who underwent biliary interventional surgery and four had a history of antibiotic exposure. Three strains were sequence type (ST)11, one was ST1, and one was ST5523. The non-CP-CRKP strains were insusceptible to ertapenem. Three strains were susceptible to amikacin. All the strains were susceptible to imipenem, meropenem, tigecycline, ceftazidime/avibatam and polymyxin B. The ß-lactamases of non-CP-CRKP predominantly included blaCTX-M, blaSHV, and blaTEM subtypes. Two site mutations in ompK36 (p.A217S and p.N218H) and four in ompK37 (p.I70M, p.I128M, p.N230G, and m233_None234insQ) were detected accounting for carbapenem resistance. Plasmids IncFI and IncFII were found in most strains. Genes encoding aerobactin, yersiniabactin and allantoin utilization were not detected in several isolates, and all non-CP-CRKP strains did not carry rmpA gene. Conclusions: Non-CP-CRKP infected patients had a history of previous antibiotic exposure or invasive procedures. Non-CP-CRKP strains were insusceptible to ertapenem. The mechanism of resistance includes ß-lactamases production and the site mutations in ompK36 and ompK37. Several virulence genes were not detected in non-CP-CRKP. [ABSTRACT FROM AUTHOR]

The efficacy of converting to oral fluoroquinolones after initial intravenous antibiotics for the treatment of acute pyelonephritis (APN) caused by the third‐generation cephalosporin resistant Enterobacteriaceae (3‐GCrEC) needs to be investigated. The objective was to compare the clinical and bacteriological outcome of oral prulifloxacin with intravenous ertapenem for the treatment of APN caused by 3‐GCrEC. A pilot, randomized controlled trial of patients with APN caused by 3‐GCrEC was conducted at two hospitals from August 2015 to December 2020. Any intravenous antimicrobial drug was initially permitted for empirical therapy. On day 4, adult patients (aged >18 years) with either non‐bacteremic or bacteremic APN were eligible for the study if their infection was caused by 3‐GCrEC susceptible to the study drugs. The patients were randomly assigned to receive either oral prulifloxacin or intravenous ertapenem. The total duration of antimicrobial therapy was 14 days. Of the 21 enrolled patients, 11 were treated with prulifloxacin, and 10 were treated with ertapenem. At the test of cure visit, there was no statistically significant difference between the patients with overall clinical success who were treated with prulifloxacin (90.9%) and those treated with ertapenem (100%, p = 0.999). In addition, there was no statistically significant difference in microbiological eradication between the prulifloxacin and ertapenem groups (100% vs. 100%, p = 0.999). The converting to oral prulifloxacin after intravenous antibiotics therapy appears to be an alternative option for treatment of APN caused by 3‐GCrEC. A further large randomized controlled trial should be investigated. [ABSTRACT FROM AUTHOR]

Purpose: Further elucidate the potential drug interaction between tacrolimus and carbapenems in order to appropriately maintain the balance between infection treatment and therapeutic immunosuppression. Methods: This study was a retrospective evaluation of solid organ transplant recipients on a stable dose of tacrolimus who received either ertapenem or meropenem. Patients were excluded if they had acute kidney injury, acute liver failure, concomitant initiation of medications that interact with tacrolimus, or were pregnant. The primary endpoint was the change in the median daily tacrolimus dose after meropenem or ertapenem administration. The secondary endpoint was the change in serum tacrolimus levels after meropenem or ertapenem administration. Results: A total of 28 patients on tacrolimus were included in the study, 12 received ertapenem and 16 received meropenem. The median daily tacrolimus dose was 4.5 mg [IQR 3.0 mg – 8.8 mg] prior to and 3.4 mg [IQR 2.3 mg – 8.8 mg] after ertapenem administration. The median daily tacrolimus dose was 3.0 mg [IQR 1.6 mg – 5.5 mg] before and 3.0 mg [IQR 1.6 mg – 5.5 mg] after meropenem administration. No statistically significant difference in regard to the change in the median daily tacrolimus dose after ertapenem (P =.173) or meropenem administration (P =.755) was observed. There was no statistically significant difference found after ertapenem (P =.583) or meropenem (P =.317) administration when comparing pre- and post-administration median serum tacrolimus levels. Conclusion: The administration of ertapenem or meropenem did not affect serum tacrolimus levels or daily tacrolimus dose suggesting against empiric dose adjustments with co-administration. [ABSTRACT FROM AUTHOR]

COVID-19 is a serious virus that can have a lot of effects, one of which is a secondary bacterial infection that can be more life-threatening and even lethal than the initial viral infection. Hence a fast and sensitive HPLC/UV method was developed and validated for the first estimation of a binary mixture of molnupiravir (MOL) and ertapenem (ERT) as a co-administrated medicine for the management of COVID-19 in pharmaceutical dosage forms, and human plasma samples. The drug combination was separated within 5 min via RP-ODS column using isocratic elution with a mobile phase of 0.05 M phosphate buffer (pH 3.5): acetonitrile with a 76: 24% ratio v/v. The presented method provided a linear response ranging from 0.03 to 17.0 and 0.05–20 µg mL−1 with LOD values of 0.009 and 0.008 µg mL−1 for MOL and ERT respectively. The good separation and high sensitivity of the HPLC method provide the determination of the cited drugs in human plasma without matrix interference with a percent of recovery ranging from 94.97 ± 2.05 to 98.44 ± 1.92. Based on the results, this method could be utilized to monitor cited drugs in quality control and therapeutic laboratories. [ABSTRACT FROM AUTHOR]

Background and Aim: Antibiotic resistance is a major global health threat. The increasing prevalence of drug-resistant bacteria poses a serious challenge to the effective treatment of infections in both humans and animals. Water is a major source of human and animal exposure to bacteria, and the presence of drug-resistant bacteria in water could present a severe threat to public health and animal production. This study investigated the presence of drug-resistant bacteria in Lam Pao Dam (LPD) water in Kalasin, Thailand. Materials and Methods: Ampicillin-resistant strains were obtained from LPD water and identified using 16s rDNA sequencing. Antibiotic resistance genes were detected by polymerase chain reaction using specific primers. The presence of antibiotic-resistant bacteria was evaluated using 16s amplicon analysis. The minimum inhibitory concentration (MIC) of Raoultella ornithinolytica strains against antibiotics was determined. Results: A total of 12 R. ornithinolytica, 4 Bacillus cereus, and 4 Enterococcus faecalis isolates were resistant to ampicillin. Almost all R. ornithinolytica strains harbored blaSHV and blaOXA genes, and two strains also harbored the blaNDM-1 gene. All four E. faecalis strains harbored the blaIMP gene. The most abundant species in the LPD sample was Exiguobacterium indicum, followed by E. faecalis and R. ornithinolytica. The MICs of 10 R. ornithinolytica strains against five antibiotics revealed that all strains were resistant to ampicillin but susceptible to meropenem, doripenem, ertapenem, and imipenem. Conclusion: These findings suggest a high prevalence of drug-resistant bacteria in LPD water. This is a cause for concern, as it could spread antibiotic-resistant infections in the community. [ABSTRACT FROM AUTHOR]

Herein, we aimed to describe the outcomes of patients with blood stream infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) who received ertapenem plus meropenem combination treatment (EMCT). A total of 53 patients with culture proven CR-Kp bacteremia treated with ertapenem + meropenem were included. The patients with secondary bacteremia due to urinary tract infection exhibited a significantly lower 1-month mortality (OMM), particularly in those with microbiological eradication and those with end-of-treatment success. Salvage EMCT resulted in 49% 1-month survival. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) poses a significant public health concern due to its potential for increased mortality and morbidity. The limited availability of effective antibiotics further exacerbates the dissemination of carbapenem-resistant bacteria. This study aimed to evaluate the prevalence of carbapenem resistance and carbapenemase production in Enterobacteriaceae isolates using the Modified Hodge Test. Methods: This observational study was conducted at the Department of Microbiology, MGM Medical College & Hospital, Aurangabad, Maharashtra, from November 2015 to November 2017. 171 Enterobacteriaceae isolates from various clinical samples were comprehensively tested for carbapenem resistance and carbapenemase production. This involved the use of carbapenem discs (ertapenem, meropenem, and imipenem), E-test strips for ertapenem and meropenem, and the Modified Hodge Test (MHT) for carbapenemase identification. Results: Among the 171 tested Enterobacteriaceae isolates, a substantial proportion (40%) displayed resistance to carbapenems, as determined by disc diffusion and E-test methods. Among the carbapenem-resistant isolates, 13 were positive for the MHT. Conclusion: Our study revealed a notable prevalence of carbapenem resistance in Enterobacteriaceae isolates from a tertiary care hospital. The MHT, following Clinical and Laboratory Standards Institute (CLSI) guidelines, demonstrated high sensitivity (> 90%) and specificity (> 90%) for detecting KPC-type carbapenemases in these isolates. Treatment options for CRE infections are limited, with tigecycline and colistin identified as potential options. Our study highlights the importance of promptly diagnosing different carbapenemases using PCR techniques. Consequently, we strongly advocate for implementing robust antimicrobial stewardship programs and infection control practices in healthcare settings to prevent CRE spread effectively. [ABSTRACT FROM AUTHOR]

A rapid phenotypic carbapenemase-producing Enterobacterales (CPE) detection method was established using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Sixtyfour carbapenem-resistant Enterobacterales (CRE) strains from Samutprakan Hospital were examined using MALDI-TOF MS by the ertapenem hydrolysis method and the susceptibility was compared with a modified carbapenem inactivation method (mCIM). Drug resistance genes were detected by polymerase chain reaction (PCR). The ertapenem drug and bacterial strains were mixed and drug hydrolysis owing to CPE activity was confirmed by specific molecular masses of ertapenem [M+H]+ at 476.5 m/z (±500 ppm), with peak disappearance judged as carbapenemase-positive. The most common CRE species were Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. From 58 CPE strains, 17 strains of K. pneumoniae (29.3%) harbored blaNDM and blaOXA- 48-like genes together, while 33 strains of K. pneumoniae (56.9%), 6 strains of E. coli (10.3%) and 1 strain of Ent. cloacae (1.75%) carried blaNDM or blaOXA-48- like genes alone and 1 strain of K. pneumoniae (1.75%) contained blaKPC. After 3 h of incubation with ertapenem, all 58 drug-resistant strains revealed disappearance of the ertapenem-specific waveform peak at 476.5 m/z, whereas 6 strains of CRE (non-CPE) revealed the ertapenemspecific waveform peak. The MALDI-TOF MS and mCIM data were 100% consistent. The MALDI-TOF MS based ertapenem hydrolysis assay was demonstrated as a rapid and accurate method to detect carbapenemase activity of Enterobacterales strains that can be routinely performed in clinical microbiology laboratories. [ABSTRACT FROM AUTHOR]

COVID-19 is a serious virus that can have a lot of effects, one of which is a secondary bacterial infection that can be more life-threatening and even lethal than the initial viral infection. Hence a fast and sensitive HPLC/UV method was developed and validated for the first estimation of a binary mixture of molnupiravir (MOL) and ertapenem (ERT) as a co-administrated medicine for the management of COVID-19 in pharmaceutical dosage forms, and human plasma samples. The drug combination was separated within 5 min via RP-ODS column using isocratic elution with a mobile phase of 0.05 M phosphate buffer (pH 3.5): acetonitrile with a 76: 24% ratio v/v. The presented method provided a linear response ranging from 0.03 to 17.0 and 0.05–20 µg mL−1 with LOD values of 0.009 and 0.008 µg mL−1 for MOL and ERT respectively. The good separation and high sensitivity of the HPLC method provide the determination of the cited drugs in human plasma without matrix interference with a percent of recovery ranging from 94.97 ± 2.05 to 98.44 ± 1.92. Based on the results, this method could be utilized to monitor cited drugs in quality control and therapeutic laboratories. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the demographic characteristics of children with perianal abscess, distribution of microbiological etiology, antibiotic susceptibility, and identify the effectiveness and coverage of antibiotics due to culture results. Methods: A retrospective study was designed to evaluate pediatric patients with perianal abscesses between January 2013 and December 2022. Results: A total of 197 episodes in 135 patients were evaluated. The median age of the patients was 10 months (22 days–17 years). The isolated microorganisms were Gram-positive bacteria in 56 (28.4%) patients and Gram-negative bacteria in 141 (71.6%) patients. The most common isolated species was Escherichia coli (n = 70, 35.5%), followed by Klebsiella spp. (n = 48, 24.4%), Staphylococcus aureus (n = 37, 18.9%), and Enterobacter spp. (n = 9, 4.5%). Forthy-two percent (n = 58) of isolates were positive for extended-spectrum beta-lactamase, 8% (n = 11) were carbapenem-resistant in Gram-negative bacteria, and 37.5% (n = 21) were methicillin-resistant, 7.1% (n = 4) were vancomycin-resistant in Gram-positive bacteria. According to bacterial culture results, ertapenem plus glycopeptide had the highest antimicrobial coverage rate (92.3%), followed by ertapenem plus clindamycin (89.8%), ertapenem (81.7%), third-generation cephalosporin plus glycopeptide (82.2%), third-generation cephalosporin plus clindamycin (69.5%). Conclusion: Ertapenem can be a good choice in the empirical treatment of perianal abscesses in children due to its high coverage rate. [ABSTRACT FROM AUTHOR]

Aims: Several cases of ertapenem‐related neurotoxicity have been published in the current literature. However, studies evaluating the ertapenem blood concentration (EBC) as a risk of these adverse events are scarce. We aimed to evaluate the relationship between the trough EBC and the risk of neurological toxicity. Methods: This was a retrospective study, including patients who underwent ertapenem treatment between October 2019 and February 2021. We excluded patients in the critical care unit and those whose blood samples were not properly taken in order to analyse ertapenem trough concentration. We also excluded patients whose clinical follow‐up was not properly realized for the entire period of ertapenem treatment. The main outcome was the presence of any suspicious neurological side effect owing to ertapenem administration and its relationship with the plasma concentration. Secondary outcomes were to identify clinical and analytical data contributing to a higher risk of neurotoxicity. Results: The initial cohort comprised 158 individuals. For the final analysis we evaluated 102 patients, reporting a neurological alteration in 13/102 (12.7%). Mean trough EBC was significantly higher in patients showing neurotoxicity in comparison with those who did not (37.8 mcg mL−1, standard deviation [SD] ± 35.7 vs. 14.6 mcg mL−1, SD ± 15.2; P =.002). In multivariable logistic regression analysis, EBC (odds ratio [OR] = 1.07; P =.006), a moderate renal insufficiency (OR = 9.2; P =.02) and a history of previous neurologic disease (OR = 9.9; P =.02) were identified as risk factors of neurological alteration during ertapenem treatment. Conclusions: In patients at risk, determining the ertapenem plasma concentration may help to minimize the risk of neurotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, including two carbapenems (meropenem and ertapenem) and four non-carbapenems (gentamicin, ciprofloxacin, cefepime, and trimethoprim/sulfamethoxazole). We generated short-read data using the Illumina NextSeq and long-read data using the ONT MinION. Four assembly methods were compared: ONT-only assembly; ONT-only assembly plus short-read polish; ONT + short-read hybrid assembly plus short-read polish; short-read only assembly. Results: Consistent with previous studies, our results suggest that the hybrid assembly produced the highest quality results as measured by gene completeness and contig circularization. However, ONT-only methods had minimal impact on the detection of AMR genes and plasmids compared to short-read methods, although, notably, differences in gene copy number differed between methods. All four assembly methods showed identical presence/absence of the blaKPC-2 carbapenemase gene for all samples. The two phenotype assays showed 100% concordant results for the non-carbapenems, but only 65% concordance for the two carbapenems. The presence/absence of AMR genes was 100% concordant with AMR phenotypes for all four non-carbapenem drugs, although only 22%—50% sensitivity for the carbapenems. Conclusions: Overall, these findings suggest that the lack of complete correspondence between CRE AMR genotype and phenotype for carbapenems, while concerning, is independent of sequencing platform/assembly method. [ABSTRACT FROM AUTHOR]

Background Third-generation cephalosporin-resistant Enterobacterales (3GCRE) are increasing in prevalence, leading to greater carbapenem consumption. Selecting ertapenem has been proposed as a strategy to reduce carbapenem resistance development. However, there are limited data for the efficacy of empirical ertapenem for 3GCRE bacteraemia. Objectives To compare the efficacy of empirical ertapenem and class 2 carbapenems for the treatment of 3GCRE bacteraemia. Methods A prospective non-inferiority observational cohort study was performed from May 2019 to December 2021. Adult patients with monomicrobial 3GCRE bacteraemia receiving carbapenems within 24 h were included at two hospitals in Thailand. Propensity scores were used to control for confounding, and sensitivity analyses were performed in several subgroups. The primary outcome was 30 day mortality. This study is registered with clinicaltrials.gov (NCT03925402). Results Empirical carbapenems were prescribed in 427/1032 (41%) patients with 3GCRE bacteraemia, of whom 221 received ertapenem and 206 received class 2 carbapenems. One-to-one propensity score matching resulted in 94 pairs. Escherichia coli was identified in 151 (80%) of cases. All patients had underlying comorbidities. Septic shock and respiratory failure were the presenting syndromes in 46 (24%) and 33 (18%) patients, respectively. The overall 30 day mortality rate was 26/188 (13.8%). Ertapenem was non-inferior to class 2 carbapenems in 30 day mortality (12.8% versus 14.9%; mean difference −0.02; 95% CI: −0.12 to 0.08). Sensitivity analyses were consistent regardless of aetiological pathogens, septic shock, source of infection, nosocomial acquisition, lactate levels or albumin levels. Conclusions Ertapenem may be of comparable efficacy to class 2 carbapenems in the empirical treatment of 3GCRE bacteraemia. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this case report is to describe spasticity and encephalopathy that developed in a multiple sclerosis patient following carbapenem administration. Summary: A 55-year-old female with multiple sclerosis developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration. This was the second time that she had developed encephalopathy following carbapenem administration. The patient gradually recovered over four days following discontinuation of carbapenem therapy. Conclusion: Carbapenem neurotoxicity, a well-documented adverse effect, has been linked to several risk factors, including central nervous system lesions. Despite this, there is little evidence describing the risk of neurotoxicity in patients with multiple sclerosis. It is important to understand the potential adverse effects of carbapenems in specific patient populations to help guide appropriate treatment of infections. [ABSTRACT FROM AUTHOR]

Background We found a carbapenem-resistant Escherichia coli without known carbapenemase-encoding genes and performed a study to identify the possible new carbapenemase. Methods The production of carbapenemase was examined using the modified carbapenem inactivation method. The strain was subjected to short- and long-read genome sequencing and the complete genome was obtained by hybrid assembly. The gene encoding a potential new OXA-type carbapenemase was cloned. The enzyme was purified and was then subjected to kinetic assays. Molecular docking analysis of the enzyme was performed using the MOE software suite. Mating experiments were attempted to obtain the plasmid carrying the corresponding gene. Results We identified and characterized a novel class D carbapenem-hydrolysing β-lactamase, OXA-1041, in a carbapenem-resistant E. coli clinical strain. OXA-1041 had 89.77% (237/264) amino acid identity with OXA-427, a known carbapenemase. By cloning in an E. coli laboratory strain, bla OXA-1041 was found to reduce susceptibility to ertapenem by 16 times (MIC 0.25 versus 0.016 mg/L) and meropenem by four times (MIC 0.06 versus 0.016 mg/L) but did not significantly reduce susceptibility to imipenem and doripenem. Enzyme kinetic measurement of purified OXA-1041 showed that OXA-1041 could hydrolyse ertapenem and meropenem with a turnover number (k cat)/Michaelis constant (K M) of 8.57 and 3.63 mM−1s−1, respectively. The complete genome contained a single plasmid (223 341 bp, IncF, containing five replicons), which was self-transmissible. bla OXA-1041 was downstream of insertion sequence IS CR1 and there were three tandem copies of IS CR1 - bla OXA-1041- creD Δ (encoding an envelope protein) on this plasmid. Conclusions The above findings suggest OXA-1041 is a new plasmid-encoded carbapenemase with preferential activity against ertapenem. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of hair-bearing intertriginous areas with a profound impact on quality of life. OBJECTIVE: We sought to determine what barriers to treatment exist among both HS experts and non-experts. METHODS: An IRB-approved, anonymous, voluntary survey was distributed to dermatologists through the HS Foundation listserv from June to September 2021. RESULTS: Eighty-eight total responses were collected from 49 (55.7%) experts and 39 (44.3%) non-experts. Statistically significant differences were found in the comfort level of treating moderate (p=0.0001) to severe (p<0.0001) disease between experts and non-experts, as well as interest in treating moderate (p=0.0001) and severe (p<0.0001) disease. Multiple barriers to developing expertise were identified (e.g., access to necessary equipment). HS experts also indicated higher levels of knowledge and experience than non-experts with several medical treatments (e.g., IV Ertapenem, p<0.0001). LIMITATIONS: We were unable to calculate response rate since listserv survey recipients were encouraged to share the survey through their personal networks. CONCLUSION: This data demonstrates statistically significant differences in levels of comfort and interest between experts and non-experts in treating moderate to severe disease, as well as differences in medical therapies utilized. Furthermore, multiple barriers to expertise were identified by both experts and non-experts. [ABSTRACT FROM AUTHOR]

Background: Recent shortages of intravenous (IV) fluids have resulted in healthcare systems converting administration of many medications from IV piggyback (IVPB) to IV push (IVP). Administering medications via IVP presents numerous advantages; however, IV site reactions such as phlebitis and infiltration may occur. Objective: The objective of this analysis is to evaluate the infusion site safety of ertapenem given as peripheral IVP compared to IVPB in adult patients. Methods: This was an institutional review board–approved, single-center, retrospective study. Patients, ages 18 or older, receiving IV ertapenem were identified. The major endpoints analyzed were IV site reactions including phlebitis and infiltration. The Naranjo Nomogram was utilized to assess the causality of the reactions to determine the likelihood of whether the event was caused by the medication itself or other factors. Results: To date, 283 administrations (92 patients) in the IVP group and 319 administrations (82 patients) in the IVPB group were analyzed. There were 13 IV site reactions compared to 8 in the IVP vs IVPB group, respectively (P -value = 0.16). Ten of the events in the IVP group were deemed "possible" and 2 deemed "doubtful," while the remaining event was considered "probable" per the Naranjo Nomogram. Of the events in the IVPB group, all 8 were found to be "possible." Conclusion: The administration of IVP ertapenem showed comparable rates of infusion site reactions compared to IVPB. Implementation of IVP ertapenem appears to be associated with infusion site safety similar to IVPB and should be considered safe to administer. [ABSTRACT FROM AUTHOR]

This study aimed to characterise E. coli strains isolated from hospital wastewater effluent in Bulawayo, Zimbabwe, using both molecular and cytological approaches. Wastewater samples were aseptically collected from the sewerage mains of a major public referral hospital in Bulawayo province weekly for one month. A total of 94 isolates were isolated and confirmed as E. coli through biotyping and PCR targeting the uidA housekeeping gene. A total of 7 genes (eagg, eaeA, stx, flicH7, ipaH, lt, and st genes) coding for virulence in diarrheagenic E. coli were targeted. Antibiotic susceptibility of E. coli was determined against a panel of 12 antibiotics through the disk diffusion assay. The infectivity status of the observed pathotypes was investigated using HeLa cells through adherence, invasion, and intracellular assay. None of the 94 isolates tested positive for the ipaH and flicH7genes. However, 48 (53.3%) isolates were enterotoxigenic E. coli (ETEC) (lt gene positive), 2 (2.13%) isolates were enteroaggregative E. coli (EAEC) (eagg gene), and 1 (1.06%) isolate was enterohaemorrhagic E. coli (EHEC) (stx and eaeA). A high level of sensitivity was observed in E. coli against ertapenem (98.9%), and Azithromycin (75.5%). The highest resistance was against ampicillin (92.6%) and sulphamethoxazole—trimethoprim (90.4%). Seventy-nine (84%) E. coli isolates exhibited multidrug resistance. The infectivity study results indicated that environmentally isolated pathotypes were as infective as the clinically isolated pathotypes for all three parameters. No adherent cells were observed using ETEC, and no cells were observed in the intracellular survival assay using EAEC. This study revealed that hospital wastewater is a hotspot for pathogenic E. coli and that the environmentally isolated pathotypes maintained their ability to colonise and infect mammalian cells. [ABSTRACT FROM AUTHOR]

Background: Emergency laparotomy for abdominal trauma is associated with high rates of surgical site infection (SSI). A protocol for antimicrobial prophylaxis (AMP) for trauma laparotomy was implemented to determine whether SSI could be reduced by adhering to established principles of AMP. Patients and Methods: A protocol utilizing ertapenem administered immediately before initiation of trauma laparotomy was adopted. Compliance with measures of adequate AMP were determined before and after protocol implementation, as were rates of SSI and other infections related to abdominal trauma. Univariable and multivariable analyses were performed to determine risk factors for development of infection related to trauma laparotomy. Results: Over a four-year period, 320 patient operations were reviewed. Ertapenem use for prophylaxis increased to 54% in the post-intervention cohort. Compliance with individual measures of appropriate AMP improved modestly. Overall, infections related to trauma laparotomy decreased by 46% (absolute decrease of 13%) in the post-intervention cohort. Multivariable analysis confirmed that treatment during the post-intervention phase was associated with this decrease, with a separate analysis suggesting that ertapenem use was an important factor in this decrease. Conclusions: Development of a standardized protocol for AMP in trauma laparotomy led to decreases in infectious complications after that procedure. [ABSTRACT FROM AUTHOR]

Background: Compliance with guideline recommendations for surgical antibiotic prophylaxis (SAP) in colorectal surgery, particularly redosing, has been suboptimal at many institutions including ours. This study aimed to evaluate if single-dose antibiotic prophylaxis with ertapenem improves compliance with guideline recommendations for SAP versus multiple-dose antibiotic prophylaxis in elective colorectal surgery. Methods: A retrospective, cohort study of the use of ertapenem compared with standard of care antibiotic agents was performed in adult patients undergoing elective colorectal surgery at an academic medical center between January 2020 and February 2022. The primary outcome was compliance with guideline-recommended SAP for colorectal surgery. The secondary outcome was surgical site infections (SSIs) within 30 days after surgery. Results: A total of 135 patients were included in this study. Fifty-eight patients received single-dose antibiotic prophylaxis with ertapenem and 77 patients received multiple-dose antibiotic prophylaxis. Cefazolin plus metronidazole was the most common multiple-dose regimen (65 of 77). Single-dose antibiotic prophylaxis with ertapenem increased overall SAP compliance (96.6% vs. 64.9%; p < 0.001) as well as compliance with antibiotic administration within the recommended time period before incision (96.6% vs. 84.4%; p = 0.022), compliance with intra-operative antibiotic redosing when warranted (100% vs. 83.1%; p < 0.001), and compliance with guideline-recommended dosing (100% vs. 92.2%; p = 0.037). Surgical site infection rates were not statistically different between the groups (12.1% vs. 19.4%; p = 0.248). Conclusions: Single-dose antibiotic prophylaxis with ertapenem increased compliance with guideline-recommended SAP for elective colorectal surgeries. No statistically significant difference was observed in SSI rates regardless of the antibiotic regimen used. [ABSTRACT FROM AUTHOR]

[Objectives] The aim of the study was to analyze the drug resistance characteristics and the production of extended spectrum beta-lactamases(ESBL)of 212 strains of Klebsiella pneumoniae for further understanding the drug resistance of these pathogens to new antibiotics, preventing the potential threat to public health and safety,and providing reference for the prevention and control of cow mastitis caused by K. pneumoniae. [Methods] K.pneumoniae was identified by the morphological observation and the PCR detection of khe gene and the analysis of 16S rRNA sequence. And the drug resistance of the isolates was detected by K-B agar plate diffusion method and micro broth dilution method. [Results] The drug resistance rates of K. pneumoniae from high to low were cefepime 5.7%, ciprofloxacin 4.7%, ceftazidime 4.2%, meropenem 2.8%, ertapenem 0.5%, imipenem 0% and tegacyclin 0%. Among the medium sensitive strains resistant to tegacyclin, all of them encoded the resistance gene ramR, but the tetX and ramA genes were not detected. Among the resistant strains to quinolone antibiotics,2 strains encoded the qnrA,6 strains encoded the qnrB,23 strains encoded the qnrS, but no strains encoded the qnrD. Among the resistant strains to β-lactams antibiotics, the carrying rates of the resistance genes SHV-1,SHV-11,SHV-34,SHV-76,SHV-171,TEM-1,CTX-M-3,CTX-M-14,CTX-M-15,CTX-M-27,CTX-M-55,CTX-M-244,ACT-6,ACT-31,DHA-1,CMY-174,CMY-81 and LEN-5 were 6.56%,9.84%,1.64%,3.28%,1.64%,27.87%,8.2%,1.64%,3.28%,1.64%,9.84%,4.92%,3.28%,1.64%,9.84%,1.64%,1.64% and 1.64% respectively. No mutation sites were detected in the above drug-resistant genes. [Conclusions] In this study, many isolates of K. pneumoniae from bovine mastitis showed high resistance to new cephalosporins and other antibiotics, several strains developed multidrug-resistance, and even were resistant to carbapenems. These results suggested that we need to guard against the generation and spread of the resistant strains to the new antibiotics, and avoid the occurrence of public health safety hazards, which raise standard for the prevention and control of K. pneumoniae from bovine mastitis. [ABSTRACT FROM AUTHOR]

Aims The antibacterial activity of red propolis extract (RPE) and brown propolis extracts (BPE) and the synergistic effect of RPE with cefoxitin (CEFO), imipenem (IMI), and ertapenem (ERTA) was evaluated in vitro against methicillin-resistant Staphylococcus aureus (MRSA) strains. Methods and results MRSA ATCC 33591, community-associated (CA-MRSA) USA300, and four clinical isolates were used. A broth microdilution assay was performed to obtain inhibitory and bactericidal concentrations of BPE, RPE, CEFO, IMI, and ERTA. RPE in combination with CEFO, IMI, and ERTA was evaluated on the formation or eradication of biofilm. The bacterial relative membrane conductivity of the strains was assessed after RPE and combinations exposition. Surface/binding computational analyzes between RPE compounds and penicillin binding protein 2a (PBP2a) were performed. BPE samples had no activity against MRSA (MICs 3.2–5 g l−1; MBCs 10–15 g l−1), so the subsequent assays were carried out only with RPE and antimicrobials. RPE exerted a bacteriostatic action (MICs 0.0156–0.125 g l−1; MBCs 0.5–2 g l−1) but the combinations with IMI and ERTA showed the highest inhibition, as observed in the time-kill curve. However, the FICI index showed synergism (≥0.5) only to RPE + IMI. This combination was the most effective in inhibiting the biofilm and showed the highest values of membrane conductivity. Computational predictions indicated that RPE constituents may interact with PBP2a. Conclusion RPE and RPE + IMI exerted an antibacterial and antibiofilm activity on MRSA strains probably due to membrane/wall damage and interactions with PBP2a. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a life-threatening pathogen that has not been fully investigated on a molecular basis. Therefore, the molecular mechanisms of carbapenem resistance in CRKP collected from medical institutions in Hyogo Prefecture has been analyzed. Antimicrobial susceptibilities and the presence of carbapenemase along with epidemiological analyzes using multilocus sequence typing (MLST) have been investigated. The relative expression of efflux pump genes and mutations of ompK35 and ompK36 , encoding the outer membrane porin, were also assessed for their relationship with carbapenem resistance. Most of the collected 22 CRKP isolates were non-susceptible to imipenem (68.2%), meropenem (90.9%), and ertapenem (81.8%), but all 22 strains were susceptible to colistin. Twelve strains (54.5%) were detected for carbapenemase genes such as bla IMP-6. Sequence type 37 was detected by MLST in 10 strains (45.5%). Non-carbapenemase-producing strains had high resistance rates for three carbapenems, and the main cause of resistance was ompK35 mutation. In conclusion, the main cause of resistance was imipenemase metallo-β-lactamase (IMP-6) production in carbapenemase-producing strains, and ompK35 mutation in non-carbapenemase-producing strains. Susceptibility to carbapenem did not differ in CRKP regardless of carbapenemase production, except for imipenem susceptibility. This result contributes to a more insightful understanding of the mechanisms of CRKP in Japan. [ABSTRACT FROM AUTHOR]

Neonatal sepsis remains a high cause of morbidity and mortality in preterm neonates. Methicillin‐susceptible Staphylococcus aureus (MSSA) can cause persistent bloodstream infections and invasive disease in neonates. We report the first published case of persistent MSSA bacteremia in a preterm neonate successfully treated with oxacillin and ertapenem combination therapy. [ABSTRACT FROM AUTHOR]

Background: Uropathogens are group of micro-organisms capable of causing urinary tract infections (UTIs). Treatment of infections due to uropathogens has become difficult because of indiscriminate use of antibiotics and ability to easily acquire resistance mechanisms by these pathogens. The objective of this study was to determine the prevalence and antimicrobial susceptibility profile of bacterial uropathogens implicated in UTI among patients attending the three Mission hospitals in Abakaliki, Ebonyi State of Nigeria. Materials & Methods: This was a descriptive study done from 1st January 2022 to 30th June 2022, in three Mission Hospitals of Nigeria 1-Rural Improvement Mission hospital, Ikwo (Hospital A); 2-Mater Misrecordea Hospital, Afikpo (Hospital B) and 3-Saint Vincent hospital, Ndubia (Hospital C) and all are located in semi-urban areas of the Ebonyi State. Inclusion criteria were urine samples of both out-patient and admit hospital patients. Both genders of all age groups patients were included. The bacterial isolates were detected using standard microbiological methods and re-confirmed using colonial morphology. Antimicrobial susceptibility profile was performed using Kirby Bauer disc diffusion. Results: Total 650 bacterial uropathogens isolates were collected from the laboratory units of the three mission hospitals and among them 529 Gram negative bacterial uropathogens were identified and re-confirmed following standard microbiological methods. Overall prevalence of uropathogens in these mission hospitals were 164 (80%), 222 (86%) and 143 (77%) from Hospital A, B and C respectively. E. coli with 58 (35%), 76 (34%) and 50 (35%) prevalence in hospital A, B and C respectively was the most prevalent and frequently isolated uropathogens. Imipenem and meropenem are the two most potent antibiotics against uropathogens in these Mission hospitals. In contrast, the isolated uropathogens developed 100% resistance to tigecycline, ertapenem, aztreonam and ampicillin/sulbactam. Conclusion: Gram negative uropathogens are predominantly the most cause of UTIs and determination of antimicrobial susceptibility profiles of bacterial uropathogens has become crucial in the treatment of UTIs. [ABSTRACT FROM AUTHOR]

REFERENCES 1 Bernabeu S, Bonnin RA, Dortet L. Comparison of three lateral flow immunochromatographic assays for the rapid detection of KPC, NDM, IMP, VIM and OXA-48 carbapenemases in Enterobacterales. We recently published a manuscript entitled 'Comparison of three lateral flow immunochromatographic assays for the rapid detection of KPC, NDM, IMP, VIM and OXA-48 carbapenemases in Enterobacterales' by Bernabeu I et al. i [1] This correspondence aimed to compare the performances of three lateral flow immunoassays (LFIAs) for the detection of carbapenemases. [Extracted from the article]

Background: OXA-48-like carbapenemases have been found in a growing and varied number of carbapenemase-producing Enterobacteriaceae (CPE) isolates, and they are spreading to several countries. Although this oxacillinase leads to weak resistance to carbapenems without affecting broad-spectrum cephalosporin activity, when they are associated with other resistance mechanisms, the level of resistance to these antibiotics may be significantly higher. This weak resistance against carbapenems and cephalosporins, along with the absence of other resistance mechanisms, could render OXA-48-like harboring isolates undetected in the laboratory routine. In addition, the lack of a specific screening test for this enzyme complicates the detection of these isolates. This report characterizes the first isolates of OXA-48-like CPE detected in our laboratory. Materials and Methods: The study was carried out at the Instituto Nacional de Enfermedades Neoplasicas, Lima - Peru, between March and December 2021. OXA-48-like CPE isolates were detected as part of the routine microbiological study, and clinical data were obtained by reviewing medical records. The automated microbiological system provides the bacterial identification and antimicrobial susceptibility profile by the dilution method. Additionally, the column chromatography test is used to detect carbapenemase enzymes, including OXA48-like. Finally, the molecular identification of the OXA-48-like enzyme was carried out by Polymerase Chain Reaction PCR amplification for the blaOXA-48-like. Results: Seven OXA-48-like CPE strains were isolated. Notably, in all cases, the automated system issued a minimum inhibitory concentration (MIC) of ≥1 ug/mL for ertapenem and a MIC of >64/4 ug/mL for piperacillin/tazobactam. In addition, resistance category to imipenem and meropenem was found (2/7), at least one indeterminate category for any of these carbapenems (5/7), and other serine β-lactamases such as Extended-spectrum beta-lactamases (3/7) and AmpC (3/7). The immunochromatographic study confirmed the presence of the OXA-48-like enzyme in all isolates, while class A and class B were ruled out for them. Finally, the multiplex PCR, for the five isolates that could be recovered, showed amplification for carbapenemase OXA-48-like, while none of the other carpabemases was amplified for class A or class B carbapenemase genes. Conclusion: We confirm the emergence of OXA-48-like CPE isolates in our cancer center and highlight the need to implement surveillance and detection measures of these strains, for controlling their dissemination. We found practical and inexpensive methodologies for the detection of OXA-48-like CPE: (1) the finding of resistance to ertapenem and piperacillin/ tazobactam in the antibiogram in the absence of class A and B carbapenemases, for screening and (2) immunochromatographic study, for confirmation. [ABSTRACT FROM AUTHOR]

Background: Extensive use of carbapenems to treat multidrug-resistant (MDR) Gram-negative bacteria (GNB) facilitates the wide dissemination of carbapenemase-producing carbapenem-resistant GNB. Colistin was reintroduced into clinical settings to manage these GNB infections. However, there is currently an increase in the dissemination of mobile colistin resistance (mcr)-producing colistin-resistant GNB isolates in clinical settings. The epidemiology of carbapenemases and mcr in Pretoria was evaluated. Methods: Clinical MDR GNB were collected and screened for carbapenemases and mcr using polymerase chain reaction (PCR); their antibiotic susceptibility profiles were elucidated using the Vitek® 2 automated system (Biomerieux, France) and microbroth dilution (for colistin). Results and Discussion: A total of 306 isolates were collected; a majority of these were Klebsiella pneumoniae (n = 208) and were collected from males (n = 158). The isolates were retrieved from a variety of infection sites, including urine, blood cultures, and rectal swabs. The Vitek 2 system found that these isolates were largely resistant to β-lactams, where 217 (70.9%) had reduced susceptibility to at least one carbapenem (ertapenem, meropenem, or imipenem), and 81 isolates (26.5%) were resistant to colistin. PCR screening identified 201 (65.7%) isolates harboring carbapenemase genes consisting of blaOXA-48 (170, 84.2%), blaNDM (31, 15.4%), blaIMP (5, 2%), blaKPC (4, 1%), and blaVIM (5, 2%). Furthermore, 14 blaOXA-48–producing isolates were coharboring blaVIM (2), blaNDM (9), blaKPC (1), and blaIMP (2) genes. Only one isolate harbored the mobile colistin resistance (mcr)-1 gene, and this is the first report of an mcr-1–producing Acinetobacter baumannii isolate in South Africa. Conclusion: There is high endemicity of carbapenemase genes and a low prevalence of mcr genes in GNB, particularly in K. pneumoniae, in health care facilities in Pretoria and surrounding regions of South Africa. Significance: Health care facilities in Pretoria are becoming breeding grounds for MDR infections that threaten public health. Careful use of carbapenems and other antibiotics is necessary to prevent further escalation and outbreak of these MDR strains that can claim several lives. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) remains a global health challenge, as bacteria display increasing resistance to last-resort antibiotics such as carbapenems. Enterobacter cloacae are evolving and developing high level of resistance to carbapenems. With increasing AMR, availability of antibiotics for treatment dwindles, hence a need to complement antibiotics to enhance activity or reduce the level of resistance. This study explored the use of calcium ions in attenuating bacterial resistance to carbapenems. Method: E. cloacae strains isolated from hospital fomites and air were subjected to antimicrobial susceptibility testing with carbapenem antibiotics (imipenem, meropenem, doripenem and ertapenem) using the disc diffusion (E. coli ATCC 25922 as control). Growth profile, Ca-Adjusted assay and time-kill curve of the strains was determined in the presence and absence of carbapenem antibiotics following a calcium stress assay. Results: Growth profile showed that all the E. cloacae strains grew markedly well at 37°C relative to ATCC 25922 and all strains displayed 80% to 100% level of resistance to tested antibiotics. The growth rate of the strains in the presence of the antibiotics was comparable to the growth rate in the absence of carbapenems. Conditional growth stress with calcium ions showed a 50% reduction in the level of resistance with doripenem displaying the lowest level of reduction and ertapenem, the highest. Discussion: The study showed that E. cloacae strains displayed high levels of resistance to carbapenems, increasing the possibility of treatment failure. Challenging strains with calcium prior to antibiotic treatment led to a significant reduction in level of resistance, indicating that calcium ions could affect bacterial strains during antibiotic activity leading to reduction in level of resistance. Conclusion: Calcium supplement could potentiate carbapenem effectiveness and reduce bacterial AMR. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial prophylaxis is a cornerstone to preventing surgical site infections (SSIs). Ertapenem, a carbapenem antibiotic, is commonly used for surgical prophylaxis for many different procedures, including patients undergoing colorectal and other gastrointestinal surgeries. Obesity complicates surgical intervention and increases the risk for SSIs. This study aims to describe the pharmacokinetics of ertapenem for surgical prophylaxis using a population pharmacokinetic model. Patients and Methods: Ten patients were recruited and given a single dose of ertapenem 1 g intravenous over 30 minutes. Plasma samples were obtained at multiple time points over 24 hours and assayed via validated high-performance liquid chromatography (HPLC). Pharmacokinetic analyses were conducted using a population pharmacokinetic analysis to generate pharmacokinetic parameters used in the subsequent 5,000 patient Monte Carlo simulation. The probability of target attainment (PTA) for free drug concentrations remaining above the minimum inhibitory concentration (MIC) for ≥40% was used. Results: The mean maximum plasma concentration and area under the concentration time curve (AUC0-∞) was 40.7 ± 16.5 and 148.8 ± 28.0, respectively, with a half-life of the terminal portion to be 4.3 ± 0.8 hours. Monte Carlo simulations observed PTAs above 90% for MICs ≤0.25 and ≤0.125 mcg/mL in surgeries up to three and four hours, respectively. Sufficiently high PTAs were not attainable for MICs of ≥0.5 mcg/mL. Conclusions: Ertapenem given as 1 g single dose may be an appropriate candidate for surgical prophylaxis in obese patients undergoing surgeries of four hours or less. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a common opportunistic pathogen causing a wide range of infections; pneumonia, urinary tract infection, bacteremia, and liver abscesses. It infects primarily immunocompromised and immunocompetent individuals. It presents itself as an antibiotic-resistant bacterium, especially for third-generation cephalosporins and carbapenems, creating serious global challenges. Therefore, this cross-sectional study was conducted in B & B Hospital, Lalitpur to screen the distribution of carbapenem resistance K. pneumoniae through ertapenem and to assess the minimum inhibitory concentration of imipenem for screened carbapenem resistance K. pneumoniae. From 3447 different clinical samples collected according to standard guidelines, K. pneumoniae was identified using standard microbiological techniques; staining and a panel of biochemical tests. The antibiotic susceptibility test of the isolates was performed by the Kirby-Bauer disc diffusion method as per CLSI 2018 guidelines. The screening of carbapenem resistance was assessed by using ertapenem disc and the MIC of imipenem for carbapenem resistance and intermediate was performed using an Epsilometer. A total of 85 K. pneumoniae were identified and their antibiotic susceptibility test revealed that ceftriaxone was the least effective antibiotic. The number of MDR, carbapenem-resistant and intermediate isolates was 51, 46, and 3, respectively. The MIC of imipenem through an Epsilometer from ertapenem resistant and intermediate revealed that 31, 5, and 13 isolates were resistant, intermediate, and sensitive respectively. These findings showed the inconsistency in the detection of carbapenem-resistant isolates in routine microbiology laboratories and further support the other tests for the detection of carbapenem resistance as suggested by CLSI. [ABSTRACT FROM AUTHOR]

The evolution of multidrug resistance in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D ß-lactamase subfamily present in Acinetobacter spp. is particularly concerning because of its ability to confer resistance to carbapenems. The kinetic profiles of class D ß-lactamases exhibit variability in carbapenem hydrolysis, suggesting functional differences. To better understand the structure-function relationship between the carbapenem-hydrolyzing class D ß-lactamase OXA-24/40 found in Acinetobacter baumannii and carbapenem substrates, we analyzed steady-state kinetics with the carbapenem antibiotics meropenem and ertapenem and determined the structures of complexes of OXA-24/40 bound to imipenem, meropenem, doripenem, and ertapenem, as well as the expanded-spectrum cephalosporin cefotaxime, using X-ray crystallography. We show that OXA-24/40 exhibits a preference for ertapenem compared with meropenem, imipenem, and doripenem, with an increase in catalytic efficiency of up to fourfold. We suggest that superposition of the nine OXA-24/40 complexes will better inform future inhibitor design efforts by providing insight into the complicated and varying ways in which carbapenems are selected and bound by class D ß-lactamases. [ABSTRACT FROM AUTHOR]

There is an increasing use of left ventricular assist devices (LVADs) as bridge to transplantation or permanent destination therapy in the heart failure patient population. Infection remains a common complication in LVADs, with Gram‐positive skin flora as predominant pathogens implicated, including Staphylococcus aureus. While there is emerging evidence for synergistic antibiotic combinations with methicillin resistant S. aureus, there remains a significant gap in the literature for persistent methicillin susceptible S. aureus bacteremia. In this article, we describe the first successful treatment of persistent LVAD‐related bacteremia with salvage oxacillin plus ertapenem. The salvage therapy described here must be balanced by the risks for toxicity, impact on resistance, microbiota disruption, drug shortages, and patient costs. This combination warrants further evaluation in the clinical setting to better establish its role in our expanding patient population. [ABSTRACT FROM AUTHOR]

Background: Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested. C:\Users\PC\OneDrive\Desktop\files\JUNE 2022\16.06.22\1VH_20220601Methods: A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work. C:\Users\PC\OneDrive\Desktop\files\JUNE 2022\16.06.22\1VH_20220601Results: FromMay2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 wereassigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i.-0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P=0.142), and secondary outcomes were similar. C:\Users\PC\OneDrive\Desktop\files\JUNE 2022\16.06.22\1VH_20220601Conclusion: The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Ertapenem is a carbapenem antibiotic usually reserved for complicated infections. Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem, and may be directly related to its chemical structure. We report a case of a 64-year-old male with a hematological history and chronic prostatitis that was admitted to hospital for gait instability, clumsiness, dysarthria and tremors. He started ertapenem intravenous 1 g once daily a week prior to admission. Creatinine clearance calculation by the Cockcroft-Gault method was 52 mL/min and total protein levels were low. Ertapenem's administration was discontinued and the patient's neurological symptoms improved dramatically just one day after. The result of the Naranjo Scale was six, suggesting a probable adverse drug reaction. We discussed if he could receive meropenem in case of severe infection such as septic shock. Considering the patient's medical history, the chemical structure of meropenem and the fact that there are almost no reported cases of neurotoxicity from this drug, we assume that meropenem could be used in case of severe infection in patients with history of neurotoxicity caused by ertapenem if no added risk factors are present, such as renal failure. [ABSTRACT FROM AUTHOR]

Background: Early appropriate antibiotic administration is associated with improved outcomes in infectious illnesses. During drug shortages in 2017, the American Society of Health-System Pharmacists recommended intravenous push (IVP) administration of medications when possible to conserve small-volume parenteral solutions. Data supporting IVP penicillins and carbapenems was limited. Objective: The primary objective of this study compared time from patient emergency department (ED) arrival to antibiotic administration between IVP and intravenous piggy-back (IVPB) administration. Methods: This single-center pre-post protocol study assessed changes in administration timing and safety of ampicillin/sulbactam, piperacillin/tazobactam, and ertapenem from 2015-2018. Medication administration by IVPB (pre) or IVP (post), ED arrival, antibiotic order and administration times, potential effectors of administration time, and safety events were assessed. Acquisition costs were estimated. Results: A total of 696 administrations were included, with 351 and 345 subjects in the IVPB and IVP cohorts, respectively. The median time from ED arrival to initiation of antibiotic administration was 140 (IQR 87-221) minutes and 110 (IQR 68-181) minutes in the IVPB and IVP cohorts, respectively, (P < 0.01). IVP administration increased the proportion of indexed antibiotics administered within 60 minutes of ED arrival compared to IVPB (20% vs. 12%, respectively, P < 0.01). There was no difference in adverse events between both cohorts. Supply acquisition cost savings totaled an more than $5,000 with the IVP protocol. Conclusion: IVP administration of ampicillin/sulbactam, piperacillin/tazobactam, and ertapenem improved times to initiation of empiric, first-dose antibiotics in the ED without an increase in adverse events, saving over $5,000 annually. [ABSTRACT FROM AUTHOR]

Background Besides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including infective endocarditis (IE). Methods MSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model. Results The median duration of bacteremia experienced by patients (n = 12) while on CZ or NAF was 4 days (range 1–16 days) compared with 1 day (range 1–3 days) for patients (n = 5) treated with ETP + CZ (P  = .01, Mann-Whitney U test). Cefazolin and NAF alone or in combination did not achieve biofilm eradication at clinically relevant concentrations. However, the addition of ETP to CZ led to bactericidal eradication within biofilms at standard dosing. Conclusions Ertapenem reduces CZ concentrations required to eradicate MSSA biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis. Larger studies are needed to investigate ETP plus CZ therapy in the treatment of biofilm-related MSSA infections such as endocarditis. [ABSTRACT FROM AUTHOR]

Background: Neisseria gonorrhoeae causes gonorrhoea, a common sexually transmitted infection. Emerging strains resistant to first-line ceftriaxone threaten N gonorrhoeae management. Hence, alternative treatments are needed. We aimed to evaluate the efficacy of ertapenem, gentamicin, and fosfomycin as alternative treatments for anogenital N gonorrhoeae.Methods: In a randomised, controlled, double-blind, non-inferiority trial (three experimental groups and one control group) at the Centre for Sexual Health in Amsterdam, Netherlands, we included adults aged 18 years or older, with anorectal or urogenital gonorrhoea. With random permuted blocks, participants were randomly assigned (1:1:1:1) to receive intramuscular 500 mg ceftriaxone (control group), intramuscular 1000 mg ertapenem, intramuscular 5 mg/kg gentamicin (maximum 400 mg), or oral 6 g fosfomycin. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the predefined primary infected site, 7-14 days after treatment. The primary analysis was per protocol (ie, excluding those lost to follow-up). The modified intention-to-treat analysis included all randomly assigned patients with anogenital gonorrhoea considering those lost-to-follow-up as treatment failure. Non-inferiority was established if the lower Hochberg-corrected 95% CI for difference between the experimental and control groups was greater than -10%. For the analysis of adverse events, we included all participants who received medication. The trial was registered at ClinicalTrials.gov (NCT03294395) and is complete.Findings: Between Sept 18, 2017, and June 5, 2020, from 2160 patients invited to participate, we assigned 346 (16%) participants to receive either ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), or fosfomycin (n=38). The fosfomycin group was terminated early after interim analysis revealed less than 60% efficacy. In the primary per-protocol analysis, 93 (100%) of 93 patients in the ceftriaxone group, 86 (99%) of 87 patients in the ertapenem group, 79 (93%) of 85 patients in the gentamicin group, and four (12%) of 33 patients in the fosfomycin group cleared N gonorrhoeae (risk difference vs ceftriaxone -0·01 [95% CI -0·08 to 0·05] for ertapenem and -0·07 [-0·16 to -0·01] for gentamicin). Thus, ertapenem proved non-inferior to ceftriaxone. In mITT analysis, risk differences versus ceftriaxone were -0·08 (-0·17 to 0·003) for ertapenem and -0·11 (-0·21 to -0·04) for gentamicin. We observed a higher proportion of patients with at least one adverse event in the ertapenem group (58 [56%] of 103) and fosfomycin group (36 [95%] of 38) versus the ceftriaxone group (24 [23%] of 103).Interpretation: Single-dose 1000 mg ertapenem is non-inferior to single-dose 500 mg ceftriaxone in gonorrhoea treatment. Yet, 5 mg/kg gentamicin (maximum 400 mg) is not non-inferior to ceftriaxone. Ertapenem is a potential effective alternative for anogenital N gonorrhoeae infections and merits evaluation for ceftriaxone-resistant infections.Funding: ZonMw and GGD-Amsterdam.Translation: For the Dutch translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Reporting of outpatient parenteral antimicrobial therapy (OPAT) outcomes with national benchmarking is key to informing service development and supporting quality improvement.Objectives: To analyse and report on data collected by the BSAC OPAT National Outcomes Registry from 2015 to 2019.Methods: Quarterly data to 2020 was extracted from the BSAC National Outcomes Registry and analysed.Results: 57 organizations submitted data on 27 841 patient episodes and 442 280 OPAT treatment days. A diverse range of infections and antimicrobials were reported with a mean OPAT treatment duration of 16.7 days (adults) and 7.7 days (paediatrics). In adults, the top five conditions treated were skin and soft tissue (27.6%), bronchiectasis (11.4%), urinary tract infections (7.6%), and diabetic foot infections (5.5%). Ceftriaxone followed by teicoplanin, ertapenem and piperacillin/tazobactam were the most-used antimicrobials. A median of 1.4 vascular-device-related complications were observed per 1000 OPAT treatment days (range 0.11 to 10.4) with device infections in 0.3 per 1000 OPAT days (range 0.1 to 1.7). Other adverse events (rash, blood dyscrasias, antibiotic-associated diarrhoea) were observed in a median of 1.9 per 1000 OPAT days. OPAT infection outcome (cured/improved) was 92.4% and OPAT outcome (success/partial success) was 90.7%.Conclusions: This report demonstrates the safety, breadth, and complexity of modern UK OPAT practice. Future analyses of OPAT data should focus on infection- and service-specific quality indicators. OPAT registries remain central to planning and assessing safe, effective, and efficient delivery of patient-centred care and should be an important focus for UK and global OPAT practice. [ABSTRACT FROM AUTHOR]