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Current antimicrobial susceptibility testing (AST) requires 16–24 hours, delaying initiation of appropriate antibiotics. Hence, there is a need for rapid AST. This study aims to develop and evaluate the feasibility of a rapid flow cytometric AST assay to determine minimum inhibitory concentration (MIC) for carbapenem-resistant Acinetobacter baumannii (CRAB). Antibiotic exposure causes increased intracellular reactive oxygen species (ROS) in bacteria. We hypothesized that ROS can be used as a marker to determine MIC. We assessed three CRAB clinical isolates across fifteen antibiotics at various concentrations in a customized 96-well microtiter plate. The antibiotics assessed include amikacin, beta-lactams (ampicillin/sulbactam, aztreonam, cefepime, ceftolozane/tazobactam, doripenem, imipenem, meropenem, and piperacillin/tazobactam), levofloxacin, polymyxin B, rifampicin, trimethoprim/sulfamethoxazole, and tetracyclines (tigecycline and minocycline). These clinical CRAB isolates were assessed for ROS after antibiotic treatment. Increased ROS levels indicated by increased RedoxSensorTM Green (RSG) fluorescence intensity was assessed using flow cytometry (FCM). MIC was set as the lowest antibiotic concentration that gives a ≥1.5-fold increase in mode RSG fluorescence intensity (MICRSG). Accuracy of MICRSG was determined by comparing against microtiter broth dilution method performed under CLSI guidelines. ROS was deemed accurate in determining the MICs for β-lactams (83.3% accuracy) and trimethoprim/sulfamethoxazole (100% accuracy). In contrast, ROS is less accurate in determining MICs for levofloxacin (33.3% accuracy), rifampicin (0% accuracy), amikacin (33.3% accuracy), and tetracyclines (33.3% accuracy). Collectively, this study described an FCM-AST assay to determine antibiotic susceptibility of CRAB isolates within 5 hours, reducing turnaround time up to 19 hours. [ABSTRACT FROM AUTHOR]

Background The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. Methods We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood–brain barrier). Results The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%–95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. Conclusions Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional limb perfusion (IVRLP) perfusate. ANIMALS 7 healthy horses. METHODS Horses received 2 IVRLPs with 2 g amikacin diluted to 60 mL with 0.9% NaCl via the cephalic vein in a crossover study design with a wash-out period between procedures. Instillation of the perfusate was administered over a 1-minute (technique 1) and 5-minute (technique 5) period. Concentrations of amikacin within the RCJ were measured at time (T) 5, 10, 15, 20, 25, and 30 minutes after instillation of the perfusate. Systemic concentrations of amikacin were measured at T0, 5, 10, 15, 20, 25, 29 minutes, and 1 minute after tourniquet removal (T31). Amikacin concentrations were determined by fluorescence polarization immunoassay. RESULTS The median maximum concentration (CMAX) of amikacin within the RCJ for technique 1 was 338.4 µg/mL (range, 60 to 4,925 µg/mL), while the median CMAX for technique 5 was higher at 694.8 µg/mL (range, 169.2 to 3,410 µg/mL; P = .398). There was a higher amikacin blood concentration over time for technique 1 compared to technique 5 (P = .004). CLINICAL RELEVANCE Administration of perfusate at different rates did not significantly affect synovial concentration of amikacin within the RCJ when performing IVRLP. However, increased systemic leakage was noted when the perfusate was administered over 1 minute, which might affect synovial concentrations in a larger group of horses. [ABSTRACT FROM AUTHOR]

Objectives To characterize and elucidate the spread of amikacin-resistant Enterobacteriaceae isolates from environmental samples on a pig farm in the UK, following the previous identification of index Salmonella isolates harbouring the rmtB gene, a 16S rRNA methylase. Methods Environmental samples were collected during two visits to a pig farm in the UK. Isolates were recovered using selective media (amikacin 128 mg/L) followed by real-time PCR and WGS to analyse rmtB -carrying Salmonella and Escherichia coli isolates. Results Salmonella and E. coli isolates harbouring the rmtB gene were detected at both farm visits. All Salmonella isolates were found to be monophasic S. enterica serovar Typhimurium variant Copenhagen of ST34. rmtB -harbouring E. coli isolates were found to be one of three STs: ST4089, ST1684 and ST34. Long-read sequencing identified the rmtB gene to be chromosomally located in Salmonella isolates and on IncFII-type plasmids in E. coli isolates. The results showed the rmtB gene to be flanked by IS 26 elements and several resistance genes. Conclusions We report on the occurrence of rmtB -harbouring Enterobacteriaceae on a pig farm in the UK. rmtB confers resistance to multiple aminoglycosides and this work highlights the need for surveillance to assess dissemination and risk. [ABSTRACT FROM AUTHOR]

To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Bordetella bronchiseptica (B. bronchiseptica) is a severe zoonotic pathogen widespread in aquaculture environments. However, information on the distribution and resistance of this pathogen remains scarce in pig farms. This study isolated and analyzed B. bronchiseptica from pig farms in central China and revealed a high frequency of resistance to this pathogen, with most strains forming biofilms. In addition, a B. bronchiseptica strain with a heteroresistant phenotype to gentamicin was isolated, which is a rare case and requires vigilance. This study enhances our understanding of the biological characteristics, such as the distribution and resistance, of B. bronchiseptica in pig farms in central China. This can provide valuable data for future related research and pathogen prevention and control. Bordetella bronchiseptica is a significant contributor to respiratory disease in pigs, leading to substantial economic losses in the swine industry worldwide. We isolated 52 B. bronchiseptica strains from 542 samples collected from pigs with atrophic rhinitis and bronchopneumonia in central China. Multi-locus sequence typing identified two prevalent sequence types: ST6 (69.23%) and ST7 (30.77%). PCR-based detection of seven virulence genes (fhaB, prn, cyaA, dnt, bteA, fla, and bfrZ) revealed that six of these genes were present in over 90% of the isolates, with bfrZ being the exception at 59.62%. Antimicrobial susceptibility testing, performed using the K-B method, demonstrated high sensitivity to enrofloxacin, polymyxin, and doxycycline but a notable resistance to tylosin, trimethoprim, tobramycin, ciprofloxacin, and amikacin. Remarkably, 86.54% of the isolates exhibited a multidrug-resistant phenotype. Notably, we successfully screened a strain of B. bronchiseptica with a heteroresistance phenotype to gentamicin using population analysis profiling, which is a rare case. Biofilm-formation assays indicated that 96.15% of the isolates possessed biofilm-forming capabilities. These findings provide crucial insights into the prevalence of B. bronchiseptica in central China, facilitating the development of effective preventive measures to safeguard both animal and human health. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae stands out as a major opportunistic pathogen responsible for both hospital- and community-acquired bacterial infections. This study comprehensively assesses the antibiotic resistance, amikacin persistent patterns, and biofilm-forming ability of 247 isolates of K. pneumoniae obtained from an intensive care unit of a tertiary hospital in Vietnam. Microdilution assays, conducted on a 96-well plate, determined the minimum inhibitory concentrations (MICs) of amikacin. Susceptibility data for other antibiotics were gathered from the antibiogram profile. Stationary-phase bacteria were exposed to 50 × MIC, and viable bacteria counts were measured to determine amikacin persistence. Biofilm forming capacity on 96-well polystyrene surfaces was assessed by biomass and viable bacteria. The prevalence of resistance was notably high across most antibiotics, with 64.8% classified as carbapenem-resistant K. pneumoniae and 81.4% as multidrug resistant. Amikacin, however, exhibited a relatively low rate of resistance. Of the isolates, 58.2% demonstrated a moderate to strong biofilm formation capacity, and these were found to be poorly responsive to amikacin. K. pneumoniae reveals a significant inclination for amikacin persistence, with ∼45% of isolates displaying an antibiotic antibiotic-survival ratio exceeding 10%. The study sheds light on challenges in treating of K. pneumoniae infection in Vietnam, encompassing a high prevalence of antibiotic resistance, a substantial ability to form biofilm, and a notable rate of antibiotic persistence. [ABSTRACT FROM AUTHOR]

Background: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra‐articular (IA) administration. Hypothesis/Objectives: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. Animals: Eight healthy neonatal foals. Methods: Foals received 3 amikacin treatment protocols: (1) IV‐only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA‐only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. Results: Foal age was a significant variable. The IV‐only protocol met or exceeded the 30‐minute plasma concentrations considered therapeutic (mean μg/mL [95% confidence interval, CI]) in 7‐ to 9‐day‐old (54.0 [52.2‐56.9]), 14‐ to 16‐day‐old (58.1 [55.2‐61.0]), and 21‐ to 23‐day‐old (66.6 [63.7‐69.6]) foals. Concurrent IV and IA protocol did not reach the 30‐minute concentration considered therapeutic in 7‐ to 9‐day‐old foals (46.5 [43.6‐49.4]) but did in 14‐ to 16‐day‐old (62.9 [60.0‐65.8]) and 21‐to 23‐day‐old (62.6 [59.7‐65.6]) foals. Conclusions and Clinical Importance: Concurrent IV and IA administration of amikacin produces 30‐minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin. [ABSTRACT FROM AUTHOR]

Background: Extremely low birth weight (ELBW) neonates (birth weight ≤ 1000 g) are at high risk to develop drug-induced acute kidney injury (AKI). However, we lack a pragmatic detection tool to capture their time-dependent (patho)physiologic serum creatinine (Scr) patterns. Pottel et al. suggested rescaling Scr by dividing Scr with the mean Scr value of the age- and sex-specific reference population. We explored if this Pottel method can detect drug-related nephrotoxicity in ELBW neonates. Methods: A previously reported dataset on Scr changes in ELBW neonates exposed to ibuprofen, amikacin, or vancomycin was updated to calculate Pottel scores for every available Scr value in the first 28 postnatal days. We hereby used previously published postnatal age-specific 50th centile values in an ELBW population. Linear mixed models were applied, analyzing Pottel scores as response variable and continuous time (day), drug exposure, and interaction thereof in the explanatory model. Results: Serum creatinine (n = 3231) observations in 201 ELBW neonates were collected. A statistically significant rise of Pottel scores was observed with ibuprofen starting from postnatal day 4. In addition, a cumulative effect of treatment with mean Pottel scores on day 0 of 1.020 and on day 3 during treatment of 1.106 (95% CI 1.068–1.145, p < 0.001) was observed, corrected for effect of antibiotics. Antibiotic administrations showed a small but statistically significant difference up to postnatal day 5. Conclusions: As rescaled Scr biomarker, the Pottel method showed a clear association with ibuprofen-exposed ELBW neonates, suggesting its applicability as a pragmatic bedside alternative tool to assess nephrotoxicity. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses a global threat to human health. Analyzing monitoring data on antimicrobial resistance can assist clinicians in making strategic decisions and promptly identifying outbreaks of antimicrobial-resistant organisms. The China Antimicrobial Surveillance Network (CHINET) was established in 2004 to monitor the trends in bacterial epidemiology and antimicrobial resistance. In this study, we analyzed the distribution and changing antimicrobial resistance profiles of Enterobacter spp. isolated from 53 hospitals across China between 2015 and 2021 using the CHINET data. Over the seven-year period, a total of 37,966 clinical isolates of Enterobacter spp. were obtained, accounted for 2.5% of all isolates and 5.7% of Enterobacteriaceae isolates. Among those isolates, Enterobacter cloacae was the most prevalent, comprising 93.7% (35,571/37,966). The majority of strains were isolated from respiratory tract samples (44.6%), followed by secretion, pus (16.4%), and urine samples (16.0%). As for patient composition, 37,966 Enterobacter spp. strains were predominantly isolated from inpatients (92.9%), whereas 7.1% were isolated from outpatients and emergency patients. Among inpatients, isolates from patients in surgical ward accounted for the highest percentage (24.4%). E. cloacae exhibited the lowest rates of resistance to amikacin, tigecycline, polymyxin B, imipenem, and meropenem (resistance rates < 8%). However, the percentage of carbapenem-resistant Enterobacter spp. was 10.0%, presenting a rising tendency over the 7-year study period. Antimicrobial resistance profiles of Enterobacter spp. isolates varied according to the department of isolation and patient age (adult or child), with the intensive care unit having the highest proportion of carbapenem-resistant Enterobacter spp. isolates. [ABSTRACT FROM AUTHOR]

Background: Magnetic nanoparticles are valued in medical applications for their distinctive properties. In this study, we synthesized magnetic nanoparticles with the aim of employing them for drug delivery. Materials and Methods: The nanoparticles were synthesized through the co-precipitation of ferric and ferrous salts. Subsequently, these nanoparticles were incorporated into a sodium alginate-gellan gum polymeric matrix and prepared into microbeads by the ionotropic gelation method. The microbeads underwent characterization through various techniques. Results and Discussion: In vitro release studies were conducted to assess the release of amikacin sulfate from the microbeads, and to examine the influence of crosslinking agents and polymer concentrations. Our findings suggest that the microbeads effectively control the release of amikacin sulfate. Conclusion: Our study demonstrates the potential of magnetic nanoparticles in drug delivery, particularly through sodium alginate-gellan gum microbeads as controlled-release carriers, offering promising prospects for medical applications. [ABSTRACT FROM AUTHOR]

Aims: Amikacin requires therapeutic drug monitoring for optimum efficacy; however, the optimal model‐informed precision dosing strategy for the area under the concentration–time curve (AUC) of amikacin is uncertain. This simulation study aimed to determine the efficient blood sampling points using the Bayesian forecasting approach for early achievement of the target AUC range for amikacin in critically ill patients. Methods: We generated a virtual population of 3000 individuals using 2 validated population pharmacokinetic models identified using a systematic literature search. AUC for each blood sampling point was evaluated using the probability of achieving a ratio of estimated/reference AUC at steady state in the 0.8–1.2 range. Results: On day 1, the 1‐point samplings for population pharmacokinetic models showed a priori probabilities of 26.3 and 45.6%, which increased to 47.3 and 94.4% at 23 and 15 h, respectively. Using 2‐point sampling at the peak (3 and 4 h) and trough (24 h) on day 1, these probabilities further increased to 72.3 and 99.5%, respectively. These probabilities were comparable on days 2 and 3, regardless of 3 and 6 sampling points or estimated glomerular filtration rate. These results indicated the higher predictive accuracy of 2‐point sampling than 1‐point sampling on day 1 for amikacin AUC estimation. Moreover, 2‐point sampling was a more reasonable approach than rich sampling. Conclusions: This study contributes to the development of an efficient model‐informed precision dosing strategy for early targeting of amikacin AUC in critically ill patients. [ABSTRACT FROM AUTHOR]

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed‐effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non‐GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug‐specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non‐GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50‐5.69) (gentamicin), 7.77 L/h (95% CI 7.26‐8.19) (amikacin) and 4.70 L/h (95% CI 4.61‐4.80) (vancomycin). Conclusions: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention. [ABSTRACT FROM AUTHOR]

Background: Vaginitis is common in women. The present study aims to identify the factors associated with aerobic vaginitis (AV) in women and evaluate the antibiotic resistance of bacteria responsible for this vaginitis. Methodology: This was a retrospective cross-sectional study of 840 patients and analysis of the results of their cytobacteriological examinations of cervicovaginal samples from January 01, 2020 to December 31, 2022 at the Centre Hospitalier Universitaire Joseph Raseta Befelatanana (CHUJRB) laboratory, Antananarivo, Madagascar. Results: Among the 840 patients, 35 had aerobic vaginitis, giving the prevalence of AV of 4.2%. Enterococcal vaginitis was the most common, representing 48.6% (n=17) cases of AV. Regarding associated factors, there was no significant difference in the prevalence of AV between women under age of 40 (4.4%, 29/653) and women over age of 40 years (3.2%, 6/187) (p=0.539); hospitalized (6.6%, 10/152) and non-hospitalized outpatients (3.6%, 25/688) (p=0.115); and pregnant (4.2%, 8/192) and non-pregnant women (4.2%, 27/648) (p=1.000). The antibiotic resistance varies from 0% (vancomycin) to 90.0% (penicillin G) for the Gram-positive bacteria and 0% (imipenem and amikacin) to 100% (cotrimoxazole, ciprofloxacin, cefixime) for Gram-negative bacteria (Pseudomonas spp) Conclusion: Cytobacteriological examination of cervicovaginal specimens in cases of genital disorders is necessary to improve the management of patients with AV in Madagascar. Similarly, empirical treatment should be properly guided and self-medication avoided, in order to limit the emergence of multidrug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Aim During liver transplantation, both hospital-acquired (HA) and community-acquired (CA) intra-abdominal infections (IAIs) are involved causing life-threatening diseases. Therefore, comparative studies of aerobic and facultative anaerobic HA-IAIs and CA-IAIs after liver transplantation surgery are necessary. Methods and results The species of detected isolates (310) from intra-abdominal fluid were identified and classified into hospital-acquired intra-abdominal infections (HA-IAIs) and community-acquired intra-abdominal infections (CA-IAIs). Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa , and Acinetobacter baumannii were the most commonly detected species. The resistant phenotypes were commonly detected among the HA-IAIs; however, the virulent phenotypes were the predominant strains of CA-IAIs. Regrettably, the resistance profiles were shocking, indicating the inefficacy of monotherapy in treating these isolates. Therefore, we confirmed the use of empirical combination therapies of amikacin and meropenem for treating all IAIs (FICI ≤ 0.5). Unfortunately, the high diversity and low clonality of all identified HA and CA-IAIs were announced with D-value in the range of 0.992–1. Conclusion This diversity proves that there are infinite numbers of infection sources inside and outside healthcare centers. [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]

Antimicrobial resistance increasingly complicates neonatal sepsis in a global context. Fosfomycin and amikacin are two agents being tested in an ongoing multicenter neonatal sepsis trial. Although neonatal pharmacokinetics (PKs) have been described for these drugs, the physiological variability within neonatal populations makes population PKs in this group uncertain. Physiologically‐based pharmacokinetic (PBPK) models were developed in Simcyp for fosfomycin and amikacin sequentially for adult, pediatric, and neonatal populations, with visual and quantitative validation compared to observed data at each stage. Simulations were performed using the final validated neonatal models to determine drug exposures for each drug across a demographic range, with probability of target attainment (PTA) assessments. Successfully validated neonatal PBPK models were developed for both fosfomycin and amikacin. PTA analysis demonstrated high probability of target attainment for amikacin 15 mg/kg i.v. q24h and fosfomycin 100 mg/kg (in neonates aged 0–7 days) or 150 mg/kg (in neonates aged 7–28 days) i.v. q12h for Enterobacterales with fosfomycin and amikacin minimum inhibitory concentrations at the adult breakpoints. Repeat analysis in premature populations demonstrated the same result. PTA analysis for a proposed combination fosfomycin‐amikacin target was also performed. The simulated regimens, tested in a neonatal sepsis trial, are likely to be adequate for neonates across different postnatal ages and gestational age. This work demonstrates a template for determining target attainment for antimicrobials (alone or in combination) in special populations without sufficient available PK data to otherwise assess with traditional pharmacometric methods. [ABSTRACT FROM AUTHOR]

This article provides information on the management and treatment of otitis externa in dogs. It emphasizes the importance of understanding the underlying factors and using a two-phase approach: reactive therapy to treat acute/chronic lesions and infection, and proactive therapy for long-term maintenance and prevention of flares. The article also highlights the use of appropriate ear cleaners and techniques, the challenges posed by biofilms, and the need for broad-spectrum anti-inflammatory treatment to reverse pathological changes. Additionally, it addresses the importance of pain management and training dogs to accept topical treatment. Overall, effective management of otitis externa can greatly improve the quality of life for dogs and their owners. [Extracted from the article]

Objective: This study aimed to identify subspecies of Mycobacterium abscessus complex (MABC) isolates from clinical samples by a molecular technique and to determine mutations responsible for macrolide and aminoglycoside resistance. We also aimed to investigate the correlation of phenotypic and molecular test results by examining the resistance to antimicrobial agents according to CLSI standard using the liquid microdilution test. Methods: 27 MABC isolates from clinical samples were examined. Molecular subspecies identification and mutations responsible for aminoglycoside (rrs mutation) and macrolide resistance (rrl mutation) were determined using the GenoType NTM-DR test. The resistance phenotypes of the strains to various antimicrobial agents were investigated by the Sensititre™ RAPMYCOI AST microdilution test. Results: Of the 27 isolates tested, 21 were M. abscessus subsp. abscessus, three were M. abscessus subsp. bolletii, and three were M. abscessus subsp. massiliense; rrs and rrl mutations were not observed in any strains. Except for one isolate, all M. abscessus subsp. abscessus strains showed the erm(41) T28 genotype, which indicates inducible macrolide resistance. The correlation between the GenoType NTM-DR and phenotypic susceptibility test results was 81% (k=0.5, p=0.02) for inducible macrolide resistance and 89% for acquired macrolide resistance. The most effective antimicrobial agents were amikacin, cefoxitin, imipenem, linezolid, and tigecycline. Conclusion: Although the GenoType NTM-DR test is reliable in identifying and detecting molecular macrolide and aminoglycoside resistance, there were discrepancies in the results. We recommend confirming the results with the phenotypic susceptibility method after growth on culture. Although the M. abscessus complex is resistant to many antimicrobial agents, it has shown high sensitivity to amikacin, cefoxitin, imipenem, linezolid, and tigecycline. High levels of inducible macrolide resistance in isolates indicate the importance of subtyping and sensitivity testing of isolates in patients where culture conversion has not been achieved. [ABSTRACT FROM AUTHOR]

As an infectious disease, tuberculosis (TB) poses a serious threat to public health. Although amikacin (AMK) is an important antibiotic for the treatment of drug-resistant TB, its resistance mechanisms are not fully understood. To investigate the role of Rv3737 gene on AMK drug susceptibility, a Mycobacterium tuberculosis (M.tb) Rv3737 knockout strain (H37Rv△Rv3737) and a Mycobacterium smegmatis (M.sm) Rv3737 overexpressing strain (Msm/pMV261-Rv3737) were used to detect their minimal inhibitory concentrations (MICs) in this study. The AMK MICs of Rv3737 knockout and overexpressing strains were 4-fold lower and 2-fold higher than those of the wild-type and empty plasmid strains, respectively. The results of clinical isolates showed that no Rv3737 gene mutation was found to be associated with AMK susceptibility, while the rrs A1401G mutation remained the main mechanism of high level of AMK resistance (MIC>32 μg/ml). There was a positive correlation between Rv3 737 mRNA expression level and AMK MIC. In the isolates with low-level AMK resistance (MIC = 4 μg/ml) without rrs A1401G mutation, the expression level of Rv3737 gene was significantly higher than those of susceptible isolates. In this study, the Rv3737 gene was reported for the first time for its effect on AMK susceptibility in M.tb. Although the rrs A1401G mutation remains the main reason of high-level AMK resistance, high expression of the Rv3737 gene was associated with low-level AMK resistance in clinical isolates. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic bacteriuria (ASB) during pregnancy can lead to symptomatic urinary tract infection (UTI), with increased fetal and maternal morbidity and mortality. We evaluated the incidence, clinical and microbiological profile, and outcome of ASB in pregnant women attending our antenatal clinic. Materials and Methods: This prospective study was conducted on 3769 pregnant women in a routine antenatal clinic at a tertiary care center. Participants were divided into two groups, ASB and non-bacteriuria. Data were collected in a standard proforma and analyzed using the software Statistical Package for the Social Sciences (SPSS) v. 20. Results: The incidence of ASB was 3.29% (124/3769). Majority of the women were in the age group of 21-30 years (78.76%, n = 89). Escherichia coli (61.06%) was the most common organism isolated. Maternal anemia (30.08% and 2.93% in the ASB and non-bacteriuria groups, respectively), low birth weight (LBW; 42.5% and 27.98% in the ASB and non-bacteriuria groups, respectively), intrauterine death (4.4% and 1.4% in the ASB and non-bacteriuria groups, respectively), and preterm delivery (37.2% and 22.31% in the ASB and non-bacteriuria groups, respectively) were were associated with ASB (P = 0.001). Conclusion: ASB was associated with maternal anemia, preterm delivery, intrauterine death, and LBW. Early detection and treatment of ASB may result in favorable maternal outcome. [ABSTRACT FROM AUTHOR]

The present study focused on the isolation and selection of identically similar bacteria from two different estuaries: polluted (KM186605) and marginally polluted (KM186603). The selected strains were tentatively identified as Bacillus anthracis using biochemical and molecular characteristics. The comparative assessments were performed based on their mercury and antibiotic resistance capabilities. The mercury removal percentages of KM186605 were 57.76, 40.88, 30.24 and 24.88%, while those of KM186603 were 45.92, 36.16, 28.15 and 21.69% respectively, at 25, 50, 75 and 100 mg−l concentrations of mercury. The antibiotic profile showed that KM186605 was susceptible to erythromycin, novobiocin, oxytetracycline, vancomycin, and amikacin. On the other hand, KM186603 was susceptible to oxytetracycline, erythromycin, novobiocin, and amikacin. The notable finding of the present investigation is that the strain screened from the polluted estuary (KM186605) showed higher mercury resistance but lower antibiotic resistance. The strain screened from a marginally polluted estuary (KM186603) exhibited lower mercury resistance and higher antibiotic resistance. Identically similar strains (Bacillus anthracis) were isolated from two different estuary ecosystems (polluted and marginally polluted estuaries). Phenotypical and genotypical similarities of the strains were characterized using biochemical analysis and genetic tools. Mercury removal efficiency and antibiotic resistance of the stains were analyzed and compared. The findings illustrated that the efficiency of the bacteria is influenced by the contaminant factors present in the respective environment. Based on the nature of pollutants, the resistance genes may be induced to develop their resistance capacity for their survival. [ABSTRACT FROM AUTHOR]

AbstractThe rise in ESBL-producing and carbapenem-resistant Gram-negative bacterial infections is alarming. Aminoglycosides remain attractive for treating urinary tract infections (UTIs). However, aminoglycosides-associated acute kidney injury (AKI) raises concerns, especially in patients with underlying renal impairment. We conducted a retrospective cohort study to evaluate the risk of AKI in patients with UTI empirically treated with amikacin. Among 395 patients (median age 41.9 years [IQR 28.3–67.1], 342 [86.6%] female), 162 (41.0%) received amikacin and 233 (59.0%) were empirically treated with other antibiotics. AKI incidence was low (5.6%) and not associated with amikacin exposure (OR 0.56, 95% CI 0.22–1.43, p = 0.23), even in those with pre-existing renal impairment or AKI on admission. The clinical outcomes (including cure by the third day, AKI, maximal creatinine, length of stay, mortality, and readmission) did not differ between the groups. Once-daily amikacin may offer a safe UTI treatment option amid increasing multi-drug resistance. [ABSTRACT FROM AUTHOR]

Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug–drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression. [ABSTRACT FROM AUTHOR]

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach. [ABSTRACT FROM AUTHOR]

Objectives To determine the in vitro activity of cefiderocol in a global collection of carbapenem-resistant Pseudomonas aeruginosa including >200 carbapenemase-producing isolates. Methods Isolates (n  = 806) from the ERACE-PA Surveillance Program were assessed. Broth microdilution MICs were determined for cefiderocol (iron-depleted CAMHB) and comparators (CAMHB). Susceptibility was interpreted by CLSI and EUCAST breakpoints and reported as percent of isolates. The MIC distribution of cefiderocol in the entire cohort and by carbapenemase status was assessed. Results In the entire cohort, cefiderocol was the most active agent (CLSI 98% susceptible; EUCAST 95% susceptible; MIC50/90, 0.25/2 mg/L). Amikacin (urinary only breakpoint) was the second most active, with 70% of isolates testing as susceptible. The percentage of isolates susceptible to all other agents was low (<50%) including meropenem/vaborbactam, imipenem/relebactam, piperacillin/tazobactam and levofloxacin. Cefiderocol maintained significant activity against the most commonly encountered carbapenemases including VIM- (CLSI 97% susceptible; EUCAST 92% susceptible) and GES (CLSI 100% susceptible; EUCAST 97% susceptible)-harbouring isolates. The cefiderocol MIC distribution was similar regardless of carbapenemase status, with MIC50/90 values of 0.5/4 mg/L, 0.5/2 mg/L and 0.25/1 mg/L for MBL, serine carbapenemase and molecular carbapenemase-negative isolates, respectively. Conclusions Cefiderocol displayed potent in vitro activity in this global cohort of carbapenem-resistant P. aeruginosa including >200 carbapenemase-harbouring isolates. Cefiderocol was highly active against MBL-producing isolates, where treatment options are limited. These data can help guide empirical therapy guidelines based on local prevalence of carbapenemase-producing P. aeruginosa or in response to rapid molecular diagnostics. [ABSTRACT FROM AUTHOR]

Objectives: Urinary tract infections (UTIs) are very common infections in humans, and Escherichia coli (E. coli) is the commonest pathogen leading to UTIs. The generation of beta-lactamase enzymes in this bacterium results in its resistance against many antibiotics. This study compares three doses of amikacin on alternate days with a daily dose of meropenem in the same period for the treatment of UTIs with E. coli in a double-blind clinical trial. Methods: The current double-blind clinical trial compares three doses of amikacin on alternate days with a daily dose of meropenem in the same period for the treatment of UTIs with E. coli. The patients were assigned to two groups: Intervention (receiving a single dose of amikacin once a day at 48-h intervals for a week, three doses) and control (receiving meropenem for 1/TDS for a week). Results: The E. coli infection frequency was 61 (21 cases of non-ESBL and 40 cases of ESBL-positive infections) and the frequency of the other infections was 52 (46%). In the patients with ESBL E. coli infection, ciprofloxacin (21; 70%) showed the highest antibiotic resistance, and nitrofurantoin (33; 91.7%) showed the highest sensitivity. The baseline variables between the control and intervention groups indicated no significant difference (p > 0.05). The frequency of signs and symptoms showed no significant difference between the amikacin and meropenem groups in the first 24 h and the first week. In the second week of follow-up, no clinical signs or symptoms were observed in the two groups. Conclusion: The results of this study showed that treatment with amikacin, 1 g q48h, for one week (three doses) has the same result as meropenem, 1 g q8h, for one week (21 doses). The results are the same for the treatment of UTIs with ESBL positive and ESBL negative. Amikacin can be used once every 48 h to treat UTIs, is less expensive and can be administered on an outpatient basis. Trial registration: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20170417033483N2 on the date 2018-02-13. [ABSTRACT FROM AUTHOR]

Objectives: To examine spatial effects in neonatal care, we conducted a retrospective cohort study to investigate the geographical distribution of antimicrobial exposure among very preterm and very low birth weight infants in Japan. Study design: We utilized a nationwide claims database in Japan to extract prescriptions of injectable antimicrobials for 41,423 very preterm and very low birth weight infants admitted within the first two days of life from April 2010 to March 2021. We identified frequently prescribed antimicrobials, revealed early neonatal exposure and neonatal exposure to each antimicrobial agent by 47 prefectures in Japan, and evaluated their spatial autocorrelation using global and local Moran's I statistics. We then scrutinized regional disparities in antimicrobial drug prescriptions. Results: The top 10 antimicrobials prescribed to very preterm and very low birth weight infants in Japan were ampicillin, amikacin, gentamicin, cefotaxime, fluconazole, ampicillin combination, micafungin, cefmetazole, cefazolin, and vancomycin. We identified northern cold spots for fluconazole exposure and southern hot spots for ampicillin, amikacin, gentamicin, and cefmetazole exposure. Geographical heterogeneity in the selection of antibacterial and antimycotic agents was observed. Conclusion: Our study revealed the geographical distribution of antimicrobial exposure among very preterm and very low birth weight infants in Japan, thus disclosing its spatial effects. Further research addressing the spatial effects of neonatal care is needed to understand how drug exposure affects the outcomes of preterm infants. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a major threat in infectious diseases due to its varied infection types and increased resistance. S. aureus could form persister cells under certain condition and could also attach on medical apparatus to form biofilms, which exhibited extremely high resistance to antibiotics. 3-Acetyl-11-keto-beta-boswellic acid (AKBA) is a well-studied anti-tumor and antioxidant drug. This study is aimed to determine the antimicrobial effects of AKBA against S. aureus and its persister cells and biofilms. The in vitro antimicrobial susceptibility of AKBA was assessed by micro-dilution assay, disc diffusion assay and time-killing assay. Drug combination between AKBA and conventional antibiotics was detected by checkerboard assay. And the antibiofilm effects of AKBA against S. aureus were explored by crystal violet staining combined with SYTO/PI probes staining. Next, RBC lysis activity and CCK-8 kit were used to determine the cytotoxicity of AKBA. In addition, murine subcutaneous abscess model was used to assess the antimicrobial effects of AKBA in vivo. Our results revealed that AKBA was found to show effective antimicrobial activity against methicillin-resistant S. aureus (MRSA) with the minimal inhibitory concentration of 4–8 µg/mL with undetectable cytotoxicity. And no resistant mutation was induced by AKBA after 20 days of consecutive passage. Further, we found that AKBA could be synergy with gentamycin or amikacin against S. aureus and its clinical isolates. By crystal violet and SYTO9/PI staining, AKBA exhibited strong biofilm inhibitory and eradication effects at the concentration of 1 ~ 4 µg/mL. In addition, the effective antimicrobial effect was verified in vivo in a mouse model. And no detectable in vivo toxicity was found. These results indicated that AKBA has great potential to development as an alternative treatment for the refractory S. aureus infections. [ABSTRACT FROM AUTHOR]

Background Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). Methods A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65–79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. Results Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P  < .0001; 200.5 vs 830.0 mg/L, P  < .0001; and 126.0 vs 408.0 mg/L, P  < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10–13 h after dose administration was dependent on eGFR (r2 = 0.6144, P  < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. Conclusion Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity. [ABSTRACT FROM AUTHOR]

Background: Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT). Methods: This retrospective monocentric analysis (1999–2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO. Results: A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [p = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin (p < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time. Conclusions: We observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO. [ABSTRACT FROM AUTHOR]

Aminoglycoside antibiotics represent the first class of successful drugs in the treatment of tuberculosis; however, mycobacteria and other bacterial species possess several drug resistance mechanisms to inactivate these natural products. In the past 15 years, a variety of amphiphilic aminoglycosides have been shown to have improved activity against infectious microorganisms and to subvert resistance mechanisms. Here, we report on four novel synthetic compounds derived from two existing potent antitubercular compounds and describe their activity against both Mycobacterium tuberculosis and Staphylococcus aureus. It was found that a decanesulfonylacetamidebased conjugate of amikacin displayed promising preliminary antitubercular activities, warranting further investigation to assess the therapeutic potential of these unique antimicrobials. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) among milk pathogens is increasing, which is a serious threat to consumers’ health. Therefore, this study aims to assess the current antibiotic profile of coliforms and Staphylococcus spp. in milk samples. For this, thirty milk samples were collected from various locations in Kathmandu district. Isolation and enumeration were done on selective media using streak-plate and pour-plate techniques, respectively. Antibiotic susceptibility testing (AST) was done by the Kirby-Bauer disk diffusion method. A total of 48 bacteria were isolated, of which 31 were coliform and 17 Staphylococcus spp. Among the coliforms, Klebsiella spp. (n=17, 54.84%) was the most predominant in both raw (n=12, 70.6%) and pasteurized milk (n=5, 29.4%), followed by E. coli and Citrobacter spp. While for Staphylococcus spp., 15 (88.24%) were S. aureus and 2 (11.76%) were coagulase negative Staphylococcus (CONS). S. aureus was dominant in raw milk (n=13) rather than pasteurized milk (n=2). The AST of coliforms showed higher resistance towards ampicillin (96.75%), followed by cefoxitin, ciprofloxacin, nalidixic acid, nitrofurantoin, piperacillin, co-trimoxazole, ceftriaxone, chloramphenicol, and amikacin in descending order. In the case of S. aureus, higher resistance was observed for penicillin G (100.00%), followed by cefoxitin, ampicillin, ceftriaxone, tetracycline, ciprofloxacin, and amikacin. Further, 12 (70.53%) S. aureus were confirmed as methicillin-resistant S. aureus (MRSA). And a total of 10 (32.25%) coliforms and 9 (52.95%) S. aureus were identified as multiple drug resistant (MDR) strains. Thus, it can be concluded that antibiotic resistance among milk isolates of the coliform and Staphylococcus spp. is highly prevalent, and these can be a potential source of incurable milk-borne infections. Thus, routine assessment of microbial quality as well as AMR surveillance should be done on milk isolates to ensure the safety of consumer’s health. [ABSTRACT FROM AUTHOR]

We investigated the effectiveness of antibiotics (amikacin, bedaquiline, linezolid, moxifloxacin, and rifampicin) on metabolically inert M. abscessus obtained under conditions of potassium deficiency in vitro. It was found that bedaquiline led to a significant decrease in the ability of bacteria to form colonies on dense media, but did not lead to their death, since it was shown that during cultivation in a liquid medium, they reverted to a state of active division and growth. Moxifloxacin had a bactericidal effect against metabolically inert bacteria, irreversibly and significantly reducing the number of viable cells in culture, which emphasizes the effectiveness of its use for the treatment of infections caused by M. abscessus. [ABSTRACT FROM AUTHOR]

Background Treatment of slowly growing non-tuberculous mycobacteria (SGM) is challenging. In vitro antimicrobial susceptibility testing (AST) is needed to optimize a multidrug regimen but requires weeks to result. Aggregated AST patterns, or an antibiogram, of SGM would be helpful to providers. Objectives We aggregated and analysed human SGM isolates sent to our laboratory from across the USA between 2018 and 2022 to describe their in vitro susceptibility patterns and construct an antibiogram. Methods SGM isolates' species/subspecies and mutations in rrs or rrl were identified by a line probe assay. AST was done primarily by broth microdilution and interpreted using the latest CLSI guideline. Mutational and AST results for SGM with ≥15 isolates were collated and analysed with descriptive statistics. Results There were 32 different species/subspecies of SGM from 10 131 isolates between January 2018 and December 2022 from across the USA, 80% of which were from organisms in Mycobacterium avium complex (MAC). Most specimens were sputum and came from Florida (2892). MAC ranged from 94% to 100% susceptible to clarithromycin, 64% to 91% to amikacin, 2% to 31% to linezolid, and 4% to 41% to moxifloxacin. Non-MAC SGM ranged from 82% to 100% susceptible to clarithromycin, 49% to 100% to amikacin, and 76% to 100% to rifabutin, but susceptibilities to other antimicrobials varied widely. WT rrs and rrl predicted >96% of phenotypic non-resistance to amikacin and clarithromycin, respectively, whereas mutant genotypes predicted >90% of phenotypic resistance. Conclusions Most SGM are likely to be susceptible to clarithromycin and amikacin, complementing their treatment guidance by mycobacterial experts. Molecular identification of resistant genotypes is accurate and helpful. This antibiogram for SGM will help providers. [ABSTRACT FROM AUTHOR]

BACKGROUND Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. METHODS In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. RESULTS A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P=0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. CONCLUSIONS Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640. opens in new tab; EUDRA Clinical Trials number, 2016-001054-17. opens in new tab.) [ABSTRACT FROM AUTHOR]

Mycobacterium avium complex (MAC) infections are a significant clinical challenge. Determining drug-susceptibility profiles and the genetic basis of drug resistance is crucial for guiding effective treatment strategies. This study aimed to determine the drug-susceptibility profiles of MAC clinical isolates and to investigate the genetic basis conferring drug resistance using whole-genome sequencing (WGS) analysis. Drug-susceptibility profiles based on minimum inhibitory concentration (MIC) assays were determined for 38 MAC clinical isolates (12 Mycobacterium avium and 26 Mycobacterium intracellulare). Mutations associated with drug resistance were identified through genome analysis of these isolates, and their phylogenetic relationships were also examined. Drug resistance, based on MIC values, was most commonly observed for moxifloxacin (81.6%), followed by linezolid (78.9%), clarithromycin (44.7%) and amikacin (36.8%). We identified specific mutations associated with resistance to amikacin. These include the rrs mutation at C464T in amikacin intermediate-resistance M. avium, and two mutations at T250A and G1453T in amikacin non-susceptible M. intracellulare. Mutations in rrl at A2058G, A2059C and A2059G were potentially linked to clarithromycin resistance. MAC clinical isolates not susceptible to linezolid exhibited mutations in rplC at G237C and C459T, as well as two rplD mutations at G443A and A489G. GyrB substitution Thr521Ala (T521A) was identified in moxifloxacin non-susceptible isolates, which may contribute to this resistance. A phylogeny of our MAC isolates revealed high levels of genetic diversity. Our findings suggest that the standard treatment regimen for MAC infections using moxifloxacin, linezolid, clarithromycin and amikacin may be driving development of resistance, potentially due to specific mutations. The combination of phenotypic and genotypic susceptibility testing can be valuable in guiding the clinical use of drugs for the treatment of MAC infections. [ABSTRACT FROM AUTHOR]

Amikacin (AMK), an antibiotic, is prescribed for treating various bacterial diseases like urinary tract infections, encephalitis, asthma and joint infections. The most significant side effects, which affect 1 to 10% of consumers, are kidney injury and ototoxicity. Several studies discussed the role of grape seed extract (GSE) in renoprotection against AMK. The current study aimed to extract Muscat of Alexandria grape seeds followed by its characterization to determine its bioactive components and elements. GSE nanoparticles was prepared and tested, in vitro, to determine its safety for the in vivo experiment. Experimental groups were control group I, AMK group II, GSE (50 mg/kg)-AMK group III, GSE (100 mg/kg)-AMK group IV, GSE NPs (25 mg/kg)-AMK group V and GSE NPs (50 mg/kg)-AMK group VI. Groups 2–6 received 100 mg/kg/day of AMK by intramuscular injection for two weeks for the induction of experimental nephrotoxicity. Groups 3–6 received daily doses of GSE or GSE NPs by oral gavage, concurrently, with AMK for two weeks. GSE was rich in polyphenol compounds like proanthocyanidins, phenolic acids like gallic and egallic acids, catechine and epicatechine. GSE NPs have a smooth surface and a size that ranged from 40 to 70 nm; and have an anti-oxidant, anti-inflammatory, anti-cytotoxic and anti-microbial in vitro effects. It reduced oxidative stress and inflammation that followed AMK administration; and attenuated the AMK-induced nephrotoxicity. GSE NPs were safe to be used in vivo as a renoprotective agent against AMK; where, it reduced the oxidative stress and inflammation. Key message: Grape seed extract was rich in polyphenol compounds like proanthocyanidins. Grape seed extract nanoparticles have a size that ranged from 40 to 70 nm. Nanoparticles were safe to be used in vivo as a renoprotective agent against AMK. [ABSTRACT FROM AUTHOR]

Simple Summary: The insect gut microbiota plays a crucial role in the host's resistance to pathogenic microorganisms and toxins. Resident microorganisms may persist for a long time and maintain a certain location due to the synthesis of antimicrobial agents (including antibiotics). We consider it one of the adaptation mechanisms of microorganisms in various communities. Not only do the uncontrolled use of antibiotics and changes in environmental conditions drastically alter the microbiota structure and give rise to resistant microorganisms, but they also cause a number of alterations in the host's physiology and its sensitivity to pathogens. This study opens up new prospects for further research into antibiotic-resistant symbiotic microorganisms, their benefits for persistence in the dynamic environment of the insect's gut, and the conditions necessary for changing their strategy and manifestation of virulent properties. Environmental pollution with antibiotics can cause antibiotic resistance in microorganisms, including the intestinal microbiota of various insects. The effects of low-dose aminoglycoside antibiotic (amikacin) on the resident gut microbiota of Galleria mellonella, its digestion, its physiological parameters, and the resistance of this species to bacteria Bacillus thuringiensis were investigated. Here, 16S rDNA analysis revealed that the number of non-dominant Enterococcus mundtii bacteria in the eighteenth generation of the wax moth treated with amikacin was increased 73 fold compared to E. faecalis, the dominant bacteria in the native line of the wax moth. These changes were accompanied by increased activity of acidic protease and glutathione-S-transferase in the midgut tissues of larvae. Ultra-thin section electron microscopy detected no changes in the structure of the midgut tissues. In addition, reduced pupa weight and resistance of larvae to B. thuringiensis were observed in the eighteenth generation of the wax moth reared on a diet with amikacin. We suggest that long-term cultivation of wax moth larvae on an artificial diet with an antibiotic leads to its adaptation due to changes in both the gut microbiota community and the physiological state of the insect organism. [ABSTRACT FROM AUTHOR]

Background and Objectives: Surgical Site Infections (SSI) are prevalent complications following surgical procedures globally. However, there is a relative scarcity of published data on SSI patterns in developing countries like India. This study aims to assess the incidence, risk factors, and antibiotic profiles of SSI pathogens, addressing this research gap. Materials & methods: In this retrospective study, a total of 441 patients who were admitted to the surgical department of a tertiary care teaching hospital in Central India from January 2016 to December 2016 were included. Patient data was gathered from hospital records using a structured data collection form. Statistical analysis was performed using SPSS software version 20.0, with a P-value of less than 0.05 indicating statistical significance. Results: The incidence of SSI in our study was 11.11 %, with associated risk factors including age, ASA class, surgeon's expertise, wound classification, prolonged surgery duration (>2 h), extended hospital stay, transfusion, and emergency surgical procedure. Klebsiella spp, Escherichia coli, Proteus spp, Acinetobacter, Staphylococcus aureus, and coagulase-negative staphylococci were the isolated pathogens, exhibiting varying levels of antibiotic resistance. Amikacin and Imipenem showed almost 100% sensitivity against all pathogens Conclusion: The incidence rate SSI fell within standard international ranges. However, approximately 50% of the isolates exhibited multi-drug resistance, limiting treatment options for patients with SSI. To address this, regular surveillance of pathogens and antibiotic susceptibility, alongside the strict implementation of protocols for antibiotic administration and operating room regulations, becomes crucial in mitigating the impact of SSI caused by drug-resistant bacterial pathogens. [ABSTRACT FROM AUTHOR]

Objective: Catheter-associated urinary tract infections (CAUTI) are common worldwide, but due to limited resources, its actual burden in low-income countries is unknown. Currently, there are gaps in knowledge about CAUTI due to lack of surveillance activities in Sierra Leone. In this prospective cohort study, we aimed to determine the incidence of CAUTI and associated antibiotic resistance in two tertiary hospitals in different regions of Sierra Leone. Results: The mean age of the 459 recruited patients was 48.8 years. The majority were females (236, 51.3%). Amongst the 196 (42.6%) catheterized patients, 29 (14.8%) developed CAUTI. Bacterial growth was reported in 32 (84%) patients. Escherichia coli (14, 23.7%), Klebsiella pneumoniae (10, 17.0%), and Klebsiella oxytoca (8, 13.6%) were the most common isolates. Most isolates were ESBL-producing Enterobacteriaceae (33, 56%) and WHO Priority 1 (Critical) pathogens (38, 71%). Resistance of K. pneumoniae, K. oxytoca, E. coli, and Proteus mirabilis was higher with the third-generation cephalosporins and penicillins but lower with carbapenems, piperacillin-tazobactam and amikacin. To reduce the high incidence of CAUTI and multi-drug resistance organisms, urgent action is needed to strengthen the microbiology diagnostic services and develop and implement catheter bundles that provide clear guidance for catheter insertion, care and removal. [ABSTRACT FROM AUTHOR]

Background: Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP. Results: All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60–70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50–70% isolates and the most effective combination was colistin-amikacin with 70% synergy. Conclusions: The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs. [ABSTRACT FROM AUTHOR]

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6′)-Ib. The blaIMP and aac (6′)-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance. [ABSTRACT FROM AUTHOR]

Amikacin is an aminoglycoside antibiotic that is frequently used for the treatment of neonatal late‐onset sepsis, for which therapeutic drug monitoring (TDM) is advised. In order to decrease the TDM associated burden of plasma sampling, a noninvasive TDM method using saliva samples was investigated. Methods: This was a prospective single‐centre, observational feasibility study with 23 premature and term neonates from whom up to 8 saliva samples were collected, together with residual plasma from clinical routine. Amikacin concentrations in saliva and plasma were quantified with liquid chromatography–tandem mass spectrometry. A population pharmacokinetic analysis was performed to develop an integrated pharmacokinetic model of amikacin in plasma and saliva and for the identification of covariates. TDM performance of different sampling regimens was evaluated using Monte Carlo simulations in a fictional cohort of representative neonates (n = 10 000). Results: Amikacin could be detected in saliva and a saliva compartment was appended to a 2‐compartment plasma model. First‐order absorption (k13) of the saliva compartment was 0.0345 h−1 with an interindividual variability of 45.3%. The rate of first‐order elimination (k30) was 0.176 h−1. Postmenstrual age had a significant negative covariate effect on k13, with an exponent of −4.3. Target attainment increased from 77.6 to 79.2% and from 79.9 to 83.2% using 1–to 5 saliva samples or 1–5 plasma samples, respectively. Conclusion: TDM of amikacin using saliva samples results in target attainment comparable to plasma samples and may be beneficial for (premature) neonates with late‐onset sepsis. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that colistin dependence frequently develops in colistin-susceptible Acinetobacter baumannii isolates. Despite resistance in parental strains, colistin-dependent mutants showed increased susceptibility to several antibiotics, which suggests the possibility of developing strategies to eliminate multidrug-resistant (MDR) A. baumannii. We investigated in vitro and in vivo efficacy of combinations of colistin and other antibiotics using MDR A. baumannii strains H08-391, H06-855, and H09-94, which are colistin-susceptible but develops colistin dependence upon exposure to colistin. An in vitro time-killing assay, a checkerboard assay, and an antibiotic treatment assay using Galleria mellonella larvae were performed. Although a single treatment of colistin at a high concentration did not prevent colistin dependence, combinations of colistin with other antibiotics at subinhibitory concentrations, especially amikacin, eradicated the strains by inhibiting the development of colistin dependence, in the in vitro time-killing assay. Only 40% of G. mellonella larvae infected by A. baumannii survived with colistin treatment alone; however, all or most of them survived following treatment with the combination of colistin and other antibiotics (amikacin, ceftriaxone, and tetracycline). Our results suggest the possibility of the combination of colistin and amikacin or other antibiotics as one of therapeutic options against A. baumannii infections by eliminating colistin-dependent mutants. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acinetobacter baumannii is a major cause of nosocomial infections and high mortality rates. Evaluation of risk factors for such resistant infections may aid surveillance and diagnostic initiatives, as well as, can be crucial in early and appropriate antibiotic therapy. OBJECTIVE: To identify the risk factors in patients with resistant A. baumannii infection with respect to controls. METHODS: Prospective or retrospective cohort and case-control studies reporting the risk factors for resistant A. baumannii infection were collected through two data sources, MEDLINE/PubMed and OVID/Embase. Studies published in the English language were included while animal studies were excluded. The Newcastle-Ottawa Scale was used to assess the quality of studies. The odds ratio of developing antibiotic resistance in patients with A. baumannii infection was pooled using a random-effect model. RESULTS: The results are based on 38 studies with 60878 participants (6394 cases and 54484 controls). A total of 28, 14, 25, and 11 risk factors were identified for multi-drug resistant (MDRAB), extensive-drug resistant (XDRAB), carbapenem-resistant (CRAB) and imipenem resistant A. baumannii infection (IRAB), respectively. In the MDRAB infection group, exposure to carbapenem (OR 5.51; 95% CI: 3.88–7.81) and tracheostomy (OR 5.01; 95% CI: 2.12–11.84) were identified with maximal pool odd's ratio. While previous use of amikacin (OR 4.94; 95% CI: 1.89–12.90) and exposure to carbapenem (OR 4.91; 95% CI: 2.65–9.10) were the foremost factors associated with developing CRAB infection. Further analysis revealed, mechanical ventilation (OR 7.21; 95% CI: 3.79–13.71) and ICU stay (OR 5.88; 95% CI: 3.27–10.57) as the most significant factors for XDRAB infection. CONCLUSION: The exposure of carbapenem, amikacin (previous) and mechanical ventilation were the most significant risk factors for multidrug, extensive-drug, and carbapenem resistance in patients with A. baumannii infection respectively. These findings may guide to control and prevent resistant infections by identifying the patients at higher risk of developing resistance. [ABSTRACT FROM AUTHOR]

Background and Objectives: Klebsiella pneumoniae is increasingly developing resistance to last-resort antibiotics such as carbapenems. This study aimed to investigate the dissemination of common carbapenemase encoding genes among 48 clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP). Materials and Methods: Antimicrobial susceptibility testing was performed by broth dilution and disc diffusion methods. The phenotypic evaluation of carbapenemase production was performed by using Modified Carbapenem Inactivation Method. Presence of carbapenemase encoding genes blaKPC, blaNDM, blaOXA-48-like, blaIMP, and blaVIM was screened by PCR. Results: Overall, carbapenemases were produced in all CRKP isolates. The blaOXA-48-like and blaNDM were the most prevalent genes detected among all and 66.6% (n=32) of CRKP isolates respectively. The blaVIM was detected in only one isolate co-harboring NDM and OXA-48-like carbapenemases. The bla KPC and blaIMP genes were not identified in any of the isolates. While tigecycline was the most active agent against CRKP isolates with low resistance rate (4.1%), high rate of resistance was observed to colistin (66.6%), amikacin (79%) and most of other tested antimicrobials. Conclusion: Our results revealed predominant prevalence of OXA-48-like and NDM carbapenemases among CRKP clinical isolates. High rate of resistance to last-resort agents such as colistin among CRKP isolates is a source of great concern. [ABSTRACT FROM AUTHOR]

Bacterial resistance to widely used antibiotics is an emerging global health issue and causes a huge problem in burn patients. Despite important developments in antimicrobial treatments, the risk of infection-associated mortality rate in burn patients is comparatively high. Escherichia coli is one of the most common causative agents of burn wound infections. Therefore, this study aimed to identify and characterize E. coli isolates from burn wounds using the VITEK 2 system and to test their antibiotic resistance to the most commonly used antibiotics with the disc diffusion method. In our study, of 147 clinical samples obtained from burn patients, 25 (%17) were detected as positive for E. coli. All these isolates were found to be resistant to cephalothin, cephradine, piperacillin, and rifampin antibiotics. The resistance to amoxicillin+clavulanic acid and ampicillin was 96% (± 8%), which was followed by amikacin and cefotaxime with a 92% (± 11%) resistance rate. On the other hand, imipenem (96% ± 8%), tetracycline (88% ± 13%), and gentamicin (76% ± 17%) were the antibiotics that showed the highest sensitivity against E. coli isolates. The multidrug-resistant bacteria are one of the main issues for clinical applications, so their characterization is vital in developing a proper treatment strategy. This study concluded that E. coli exists in burn wounds and might cause wound infection due to its resistance to different antibiotics. [ABSTRACT FROM AUTHOR]