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Background: Only about 50% of intensive care unit (ICU) patients reach a free trough concentration above MIC (100% fT > MIC) of beta-lactam antibiotics. Although dose adjustments based on therapeutic drug monitoring (TDM) could be beneficial, TDM is not widely available. We investigated serum creatinine-based estimated GFR (eGFR) as a rapid screening tool to identify ICU patients at risk of insufficient exposure. Method: Ninety-three adult patients admitted to four ICUs in southeast Sweden treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Beta-lactam trough concentrations were measured. The concentration target was set to 100% fT > MICECOFF (2, 4, and 16 mg/L based on calculated free levels for meropenem, cefotaxime, and piperacillin, respectively). eGFR was primarily determined via Chronic Kidney Disease–Epidemiology Collaboration (CKDEPI) and compared to three other eGFR equations. Data was analysed using logistic regression and receiver operative characteristic (ROC) curves. Results: With intermittent standard dosing, insufficient exposure was common in patients with a relative eGFR ≥48mL/ min/1.73m² [85%, (45/53)], particularly when treated with cefotaxime [96%, (24/25)]. This eGFR cut-off had a sensitivity of 92% and specificity of 82% (AUC 0.871, p < 0.001) in identifying insufficient exposure. In contrast, patients with eGFR <48mL/min/1.73m² had high target attainment [90%, (36/40)] with a wide variability in drug exposure. There was no difference between the four eGFR equations (AUC 0.866–0.872, cut-offs 44–51 ml/min/1.73m² ). Conclusion: Serum creatinine-based eGFR is a simple and widely available surrogate marker with potential for early identification of ICU patients at risk of insufficient exposure to piperacillin, meropenem, and cefotaxime. [ABSTRACT FROM AUTHOR]

Abstract Background Self-reported penicillin allergy labels are common and often inaccurate after assessment. These labels can lead to reduced use of first-line beta-lactam antibiotics and worse outcomes. We measured the impact of a previously performed inpatient proactive systematic penicillin allergy de-labelling program on subsequent antibiotic use. This prior program included assessment, risk-stratification, and low risk direct oral amoxicillin challenge. Methods We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses in Ottawa, Canada across two penicillin de-labelling intervention periods across April 15th to April 30th, 2021, and February 15th to March 8th, 2022. Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics and multivariate regression analyses were performed. Results A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention groups had sustained penicillin allergy label removal at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p

BackgroundThe microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.ResultsWe characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.ConclusionsAs we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.

Background: Self-reported penicillin allergy labels are common and often inaccurate after assessment. These labels can lead to reduced use of first-line beta-lactam antibiotics and worse outcomes. We measured the impact of a previously performed inpatient proactive systematic penicillin allergy de-labelling program on subsequent antibiotic use. This prior program included assessment, risk-stratification, and low risk direct oral amoxicillin challenge. Methods: We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses in Ottawa, Canada across two penicillin de-labelling intervention periods across April 15th to April 30th, 2021, and February 15th to March 8th, 2022. Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics and multivariate regression analyses were performed. Results: A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention groups had sustained penicillin allergy label removal at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs.15 [7.7%], p = 0.04) and were prescribed more frequently amongst those who received at least one antibiotic (28/46 [60.9%] vs.15/40 [37.5%], p = 0.097). In a multivariate regression analysis, the intervention groups were found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95%CI 1.29–5.02) and in those prescribed at least one antibiotic (OR 2.44, 95%CI 1.00–6.15). No drug-related adverse events were reported. Conclusions: Proactive penicillin allergy de-labelling for inpatients was associated with a reduction in penicillin allergy labels and increased utilization of beta-lactams in the subsequent 6-months. [ABSTRACT FROM AUTHOR]

Background: Antibacterial drugs are successful in combating most types of infections. Irrational use and higher consumption of these drugs can give rise to the antibiotic resistance globally. Objective: To evaluate antibacterial drug prescribing patterns and antibiogram in infectious disease cases admitted to the hospital. Methods: A cross-sectional, observational study was conducted from September 2019 to February 2020 among inpatients ward at the hospital after ethical approval. All the data was analysed by the mean and percentage values using Microsoft excel. Results: Out of 250 admitted patients, males and females were 156 (62%) and 94 (38%) respectively. The majority of patients 79 (32%) belonged to the age group of 20–40 years. The majority of prescriptions reported were for viral fever 48 (19%), lower respiratory tract infections 40 (16%) and dengue 33 (13%). Antibacterial drugs administered through the intravenous route and the oral route were 301 (83%) and 63 (17%) respectively. The most frequently utilized antibacterial drugs were beta-lactam class ceftriaxone 149 (60%) and the fixed-dose combination, amoxicillin plus clavulanic acid 65 (26%). Further highly prescribed antibacterial drugs were metronidazole 52 (21%), azithromycin 36 (15%), and levofloxacin 24 (10%). In Gram-negative bacteria, Escherichia coli 6 (30%) contributed majorly, while in Gram-positive coagulase-negative, Staphylococci 6 (30%) contributed the highest growth of bacteria for the specific infections in the admitted cases. Conclusion: Ceftriaxone and the amoxicillin-clavulanic acid combination were highly prescribed among all antibacterial drugs, followed by metronidazole and azithromycin. The current study showed that in the antibiogram pattern, Escherichia coli and coagulase-negative Staphylococci contributed significantly as causative organisms for infectious disease cases. The present study highlighted demographic distribution, infectious diseases with their antibacterial drug utilization patterns and antibiogram assessment in the admitted patients. [ABSTRACT FROM AUTHOR]

Patients with augmented renal clearance (ARC) are a subset of critically ill patients including burn patients that exhibit increased renal elimination of medications beyond that of similarly injured patients. Currently approved maximum regimens of medications primarily eliminated by the kidney, such as cefepime (>90% unchanged in the urine), may be inadequate (eg, compromising the bactericidal activity of cefepime) in patients with ARC. Due to recent resource limitations, centers have changed infusion practices of commonly prescribed medications to intravenous push (IVP), potentially exacerbating the problem of maintaining bactericidal cefepime concentrations. The hypothesis of the study was patients with ARC are not currently achieving adequate target attainment, when receiving cefepime 2 g every 8 h IVP. Eight blood samples were collected from each patient, and concentrations measured via LC–MS/MS. WinNonlin (version 8.3) was used to estimate the pharmacokinetic parameters of cefepime and simulate plasma concentrations of cefepime in each of the ten subjects. Simulations of cefepime plasma concentrations produced by a 2 g dose given every 8 h and a 1 g dose given every 4 h were performed and the time above a MIC of 4 mg/L, 8 mg/L, and 16 mg/L compared. The 2 g every 8 h regimen remained above the breakpoints for 92%, 85%, and 71% of the dosing interval, respectively. The 1 g every 4 h regimen remained above the same breakpoints at a frequency of 100%, 99%, and 92% of the dosing interval. Giving cefepime 1 g every 4 h is a simple approach to increase the likelihood of maintaining the optimal bactericidal activity of cefepime in patients with ARC. [ABSTRACT FROM AUTHOR]

β-lactam antibiotics are amongst the most commonly prescribed medications in the Emergency Department (ED) due to their role in empiric sepsis therapy; however, inferior therapeutic options are often utilized due to a reported allergy; penicillin (PCN) being most frequent. In the United States, 10% of the population endorses an allergic reaction to PCN while <1% experience IgE-mediated reactions. This study aimed to evaluate the frequency and outcome of patients in the ED whose PCN allergies were challenged with β-lactam antibiotics. We conducted a retrospective chart review of patients in the ED at an academic medical center aged ≥18, and who received a β-lactam despite a reported PCN allergy between January 2015 and December 2019. Patients who did not receive a β-lactam or did not report a PCN allergy prior to administration were excluded. The primary outcome was the frequency of IgE-mediated reactions in response to β-lactam administration. A secondary outcome assessed the frequency of continuation of β-lactams upon admission from the ED. 819 patients were included (66% female) with prior reported PCN reactions: hives (22.5%), rash (15.4%), swelling (6.2%), anaphylaxis (3.5%), other (12.1%), or undocumented on medical electronic record (40.3%). No patients experienced an IgE-mediated reaction to the β-lactam administered in the ED. Previously reported allergies had no effect on the continuation of β-lactams when admitted or discharged (OR: 1, 95% CI: 0.7–1.44). Patients who had a history of an IgE-mediated penicillin allergy were frequently continued (77%) on a β-lactam after leaving the ED via admission or discharge. β-lactam administration in patients with previously reported PCN allergies did not result in any IgE-mediated reactions nor in an increase in adverse reactions. Our data contributes to the body of evidence that supports the administration of β-lactams to patients with documented PCN allergies. [ABSTRACT FROM AUTHOR]

Aeromonas species are Gram-negative bacteria that infect various living organisms and are ubiquitously found in different aquatic environments. In this study, we used whole genome sequencing (WGS) to identify and compare the antimicrobial resistance (AMR) genes, integrons, transposases and plasmids found in Aeromonas hydrophila, Aeromonas caviae and Aeromonas veronii isolated from Indian major carp (Catla catla), Indian carp (Labeo rohita), catfish (Clarias batrachus) and Nile tilapia (Oreochromis niloticus) sampled in India. To gain a wider comparison, we included 11 whole genome sequences of Aeromonas spp. from different host species in India deposited in the National Center for Biotechnology Information (NCBI). Our findings show that all 15 Aeromonas sequences examined had multiple AMR genes of which the Ambler classes B, C and D β-lactamase genes were the most dominant. The high similarity of AMR genes in the Aeromonas sequences obtained from different host species point to interspecies transmission of AMR genes. Our findings also show that all Aeromonas sequences examined encoded several multidrug efflux-pump proteins. As for genes linked to mobile genetic elements (MBE), only the class I integrase was detected from two fish isolates, while all transposases detected belonged to the insertion sequence (IS) family. Only seven of the 15 Aeromonas sequences examined had plasmids and none of the plasmids encoded AMR genes. In summary, our findings show that Aeromonas spp. isolated from different host species in India carry multiple AMR genes. Thus, we advocate that the control of AMR caused by Aeromonas spp. in India should be based on a One Health approach. [ABSTRACT FROM AUTHOR]

Aeromonas species are Gram-negative bacteria that infect various living organisms and are ubiquitously found in different aquatic environments. In this study, we used whole genome sequencing (WGS) to identify and compare the antimicrobial resistance (AMR) genes, integrons, transposases and plasmids found in Aeromonas hydrophila, Aeromonas caviae and Aeromonas veronii isolated from Indian major carp (Catla catla), Indian carp (Labeo rohita), catfish (Clarias batrachus) and Nile tilapia (Oreochromis niloticus) sampled in India. To gain a wider comparison, we included 11 whole genome sequences of Aeromonas spp. from different host species in India deposited in the National Center for Biotechnology Information (NCBI). Our findings show that all 15 Aeromonas sequences examined had multiple AMR genes of which the Ambler classes B, C and D β-lactamase genes were the most dominant. The high similarity of AMR genes in the Aeromonas sequences obtained from different host species point to interspecies transmission of AMR genes. Our findings also show that all Aeromonas sequences examined encoded several multidrug efflux-pump proteins. As for genes linked to mobile genetic elements (MBE), only the class I integrase was detected from two fish isolates, while all transposases detected belonged to the insertion sequence (IS) family. Only seven of the 15 Aeromonas sequences examined had plasmids and none of the plasmids encoded AMR genes. In summary, our findings show that Aeromonas spp. isolated from different host species in India carry multiple AMR genes. Thus, we advocate that the control of AMR caused by Aeromonas spp. in India should be based on a One Health approach.

Background: The prevalence of adverse drug reactions is likely to increase, and it is associated with increased usage of various drugs. Adverse Cutaneous Drug Reaction (ACDR) is the most frequent adverse drug reaction (30–45%). In Indonesia, the study on the prevalence of ACDR is still limited. Purpose: This study investigated the prevalence, clinical features, causative agents, and mortality rate of ACDR with a type-IV hypersensitivity reaction among patients attending the Department of Dermatology and Venereology in Dr. Sardjito Hospital, Yogyakarta. Methods: This retrospective study was conducted examining medical records undertaken for five years (2011–2015). Of 68,375 patients medicated in the Department of Dermatology and Venereology, 397 patients were diagnosed as ACDR with a type-IV hypersensitivity reaction. Detailed history, including age, sex, past history, and family history of drug reaction taken by the patient, were obtained. Patch testing was done wherever feasible. Result: Of 68,375 patients, 397 patients were included in ACDR with type-IV hypersensitivity (0.58%), giving a 5% of mortality rate. The mean age of the patients was 40.42 years (±16.30; range 18 to 89 years). The female to male ratio was 1.1: 1. The Maculopapular rash was the most common ACDR manifestation (50.88%), followed by Stevens-Johnson Syndrome (13.85%), Fixed Drug Eruption (12.85%), and Drug Reaction with Eosinophilia and Systemic Symptoms (10.08%). The most common causative agents were beta-lactam (16.55%), NSAIDs (12.18%), and acetaminophen (8.62%). Conclusion: Prescription of those drugs should be considered carefully so the incidence of ACDR can be reduced.

Artemisinin and its derivatives had played a biocidal role in biomedical remedies, while they were expected to enhance the activity of antibiotics against multiple drug-resistant (MDR) bacteria. The current study evaluated the interaction of artemisinin (ART), dihydroartemisinin (DHA), artesunate (AS), and artemisinic acid (AA) with β-lactam and fluoroquinolones antibiotics against Escherichia coli. Antibiotic strip test (E-test), Kirby Bauer's disc test (KB method), and broth microdilution method were adopted for susceptibility analysis, while the checkerboard method was applied to assess synergisms. ART, DHA, AS, and AA showed significantly enhanced antibacterial effects of β-lactam antibiotics against different strains of E. coli. The study showed ciprofloxacin to be most effective by presenting the least MIC (0.017125 ± 0.0022 μg/ml), while oxacillin was least effective (MIC 256 μg/ml) against E. coli. Synergism between AA and penicillin G (75%), ampicillin (25%), and oxacillin (50%) was observed in all isolates tested. AA and AS significantly decreased the MIC of ampicillin (−0.912 ± 0.908 μg/ml) and ciprofloxacin (−0.901 ± 0.893 g/ml), respectively. Artemisinin and its derivatives increased antibiotic accumulation within E. coli in a dose-dependent manner. The time-kill assay significantly reduced the bacterial number within 24 h of incubation. The study thus concludes greater room for improvement in enhancing the efficacy of antibiotics if used with artemisinin and its derivatives.

The Tol-Pal system is a transenvelope complex widely conserved among Gram-negative bacteria. It is recruited to the septal ring during cytokinesis, and its inactivation causes pleiotropic phenotypes mainly associated with the division process. From our genetic screen to identify factors required for delaying lysis upon treatment of beta lactams, we discovered that the tol-pal mutant shares similar defects with mutants of the major class A PBP system (PBP1b-LpoB) in terms of lysis prevention. Further phenotypic analyses revealed that the Tol-Pal system plays an important role in maintaining cell integrity not only during septation, but also during cell elongation. Simultaneous inactivation of the Tol-Pal system and the PBP1b-LpoB system leads to lysis during cell elongation as well as during division. Moreover, production of the Lpo activator-bypass PBP1b, but not wild-type PBP1b, partially suppressed the Tol-Pal defect in maintaining cell integrity upon treatment of mecillinam specific for the Rod system, suggesting that the Tol-Pal system is likely to be involved in the activation of aPBP by Lpo factors. Overall, our results indicate that the Tol-Pal system plays an important role in maintaining cell wall integrity during elongation in addition to its multifaceted roles during cytokinesis. [ABSTRACT FROM AUTHOR]

The Tol-Pal system is a transenvelope complex widely conserved among Gram-negative bacteria. It is recruited to the septal ring during cytokinesis, and its inactivation causes pleiotropic phenotypes mainly associated with the division process. From our genetic screen to identify factors required for delaying lysis upon treatment of beta lactams, we discovered that the tol-pal mutant shares similar defects with mutants of the major class A PBP system (PBP1b-LpoB) in terms of lysis prevention. Further phenotypic analyses revealed that the Tol-Pal system plays an important role in maintaining cell integrity not only during septation, but also during cell elongation. Simultaneous inactivation of the Tol-Pal system and the PBP1b-LpoB system leads to lysis during cell elongation as well as during division. Moreover, production of the Lpo activator-bypass PBP1b, but not wild-type PBP1b, partially suppressed the Tol-Pal defect in maintaining cell integrity upon treatment of mecillinam specific for the Rod system, suggesting that the Tol-Pal system is likely to be involved in the activation of aPBP by Lpo factors. Overall, our results indicate that the Tol-Pal system plays an important role in maintaining cell wall integrity during elongation in addition to its multifaceted roles during cytokinesis.

Background: Diarrhea is one of the most important causes of children mortality in developing countries. Gastroenteritis causes mortality in children younger than five years old annually. The presence of antibiotics resistance species among these bacteria are major health problems. Objective: This study aimed to determine the antibiotic susceptibility and MIC50%, MIC90% of Yersinia to three beta-lactam antibiotics. Methods: This experimental study was determined sensitivity of different species of Yersinia to three beta-lactam antibiotics (Ampicillin-Cefazolin-Cefotaxime). In total 50 species (39 from different human sources, environments, foods and 11 from Pasteur institutions in Paris) were used. Minimum inhibitory concentration (MIC) was carried out by serial dilution method. Findings: Among three tested antibiotics, the lowest MIC 50%, MIC 90% were obtained for Cefotaxime (≤0.125μg/ml and 0.5μg/ml). All the tested species showed resistance to Ampicillin and very low sensitivity toward Cefazolin. Conclusion: The results showed that Cefotaxime was more effective against Yersinia species in compared to Ampicillin and Cefazolin.

Five compounds containing (2,4,5-triphenyl triphenyl-1H-) and azetidinone (beta-lactam) moiety were synthesized. The physical data and yield of synthesized compounds were recorded, the chemical structure of prepared compounds were characterized using FT-IR, ¹H-NMR and elemental analysis. The antibacterial activity was evaluated using disc diffusion method that involve tow Gram positive (staph. aureus, E. Faecalis), two Gram negative (E. coli and K. pneumoniae), and one anaerobic bacteria (streptococcus. Pyogen). Different concentration of the prepared compounds has been used, and the obtained result were compared with standard (ceftazidime). Compound (5c) showed the best antibacterial activity against all bacterial species while 5a and 5e does not. Other compounds showed activity against some species. [ABSTRACT FROM AUTHOR]

Background Urinary tract infections (UTIs) are among the most common bacterial infections. Options for initial treatment of pyelonephritis or UTI requiring hospitalization include levofloxacin (LVF) or extended-spectrum cephalosporins. Globally, uropathogenic Escherichia coli resistance rates to fluoroquinolones have increased in recent years. Objective To compare clinical outcomes of patients receiving ceftriaxone (CTX) to those who received LVF empirically for the treatment of E. coli UTI. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective, single center, cohort study of adults with a urine culture positive for E. coli who received either IV LVF or CTX empirically for the treatment of UTI. Main outcome measure The primary outcome was hospital length of stay. Secondary outcomes include time to susceptible therapy (TsT), hospital cost, and susceptibility to empiric therapy. Results There was no statistically significant difference in LOS or hospital cost. Subgroup analysis compared patients that received concordant CTX treatment and patients that received discordant LVF treatment. Patients that received concordant CTX treatment had a nonsignificant shorter median LOS (4.16 vs. 6.34 days). Median hospital cost was lower ($4345 vs. $8462, p = 0.004) and median TsT was shorter (5.83 vs. 64.46 h, p < 0.001) in the concordant CTX group. Conclusion Choice of empiric antibiotic therapy should be based on local antibiogram data. For patients with UTI requiring hospitalization, CTX seems to be an effective empiric therapy for most patients. More data is required to examine the effectiveness of local and source specific antibiograms on clinical outcomes when guiding treatment of patients with UTI. [ABSTRACT FROM AUTHOR]

Background: Previous data suggest that up to one-third of patients classified as allergic based on positive penicillin skin tests have a vague reaction history. Direct oral challenge (DOC) has been recommended for patients with a low-risk reaction history. A variety of published models stratify reaction risk to guide the use of DOC., Objective: To reassess the proportion of penicillin skin test-positive patients with vague or low-risk reaction histories and evaluate the relationship between the reaction risk history and the likelihood of positive skin test results., Methods: We identified patients who underwent penicillin allergy evaluation over a 5-year period. We recorded drug reaction history, demographic variables, skin testing, and challenge results. Matched controls whose skin tests were negative were identified for skin test-positive patients. Drug reaction histories were assigned a risk category based on 2 previously published risk stratification models. We used logistic regression to investigate whether reaction history risk was associated with positive skin test results., Results: Penicillin skin testing was performed in 3382 patients; 207 (6.1%) were positive. Positive skin tests were more frequent in outpatients (P < .001), younger patients (P < .001), and female patients (P < .001). Percentages of each risk category in each model were similar in cases versus matched controls. The likelihood for positive skin tests increased with a high-risk reaction history in one stratification model., Conclusion: Our data confirm that a substantial proportion of patients who self-report penicillin allergy and have positive skin test results have a low-risk history and imply that penicillin skin testing is associated with a poor positive predictive value., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was conducted to determine whether critically ill patients admitted to the intensive care unit (ICU) with sepsis and septic shock may benefit from extended infusion of ampicillin/sulbactam compared with those receiving intermittent infusion., Material and Methods: This randomized assessor-blinded clinical trial was conducted in the ICUs of Nemazee and Shahid Rajaee hospital, Shiraz, Iran, from August 2019 to August 2021. The participants randomly received 9 g Ampicillin/Sulbactam every 8 h by either extended (infused over 4 h) or intermittent (infused over 30 min) intravenous infusion if their estimated glomerular filtration rate based on Cockrorft-Gault formula was higher than 60 ml/min., Results: Totally, 136 patients were enrolled and allocated to the intervention and control groups, each with 68 patients. Clinical cure was significantly higher in the extended group (P = 0.039), but ICU and hospital length of stay did not differ between the groups (P = 0.87 and 0.83, respectively). The ICU (P = 0.031) and hospital (P = 0.037) mortality rates in the extended infusion group were significantly lower than those in the intermittent infusion group., Conclusion: These data should be replicated in larger clinical trials before providing any recommendation in favor of this method of administration in clinical practice., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Resistance to broad spectrum β lactams, mediated by extended spectrum beta lactamase (ESβL) and AmpC βL enzymes is an increasing problem worldwide. Presence of these in clinical infections can result in treatment failure if one of the second or third generation cephalosporins is used. Therefore, it is recommended that any ESβL-producing organism according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria can be reported as resistant to all extended spectrum β lactam antibiotics regardless of the susceptibility test results. In this study, a total of 250 Escherichia coli (E. coli) isolates were subjected to Double disc test and AmpC disc test for the detection of ESβL- and AmpC βL-producing strains, respectively. Prevalence of ESβL- and AmpC βL-producing strains among E. coli isolates, over a 3-month-period in the hospital-based population of Jaipur, was 64.80% (162/250). AmpC βL producers were 24.00% (60/250) and co-existence of ESβL and AmpC βL was detected in 8.00% (20/250) of the isolates.

Artemisinin and its derivatives had played a biocidal role in biomedical remedies, while they were expected to enhance the activity of antibiotics against multiple drug-resistant (MDR) bacteria. The current study evaluated the interaction of artemisinin (ART), dihydroartemisinin (DHA), artesunate (AS), and artemisinic acid (AA) with β-lactam and fluoroquinolones antibiotics against Escherichia coli . Antibiotic strip test ( E -test), Kirby Bauer's disc test (KB method), and broth microdilution method were adopted for susceptibility analysis, while the checkerboard method was applied to assess synergisms. ART, DHA, AS, and AA showed significantly enhanced antibacterial effects of β-lactam antibiotics against different strains of E. coli . The study showed ciprofloxacin to be most effective by presenting the least MIC (0.017125 ± 0.0022 μg/ml), while oxacillin was least effective (MIC 256 μg/ml) against E. coli . Synergism between AA and penicillin G (75%), ampicillin (25%), and oxacillin (50%) was observed in all isolates tested. AA and AS significantly decreased the MIC of ampicillin (-0.912 ± 0.908 μg/ml) and ciprofloxacin (-0.901 ± 0.893 g/ml), respectively. Artemisinin and its derivatives increased antibiotic accumulation within E. coli in a dose-dependent manner. The time-kill assay significantly reduced the bacterial number within 24 h of incubation. The study thus concludes greater room for improvement in enhancing the efficacy of antibiotics if used with artemisinin and its derivatives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ul Haq, Wang, Guo, Aqib, Muneer, Saqib, Ahmad, Ghafoor, Iftikhar, Chen and Liang.)

Streptococcus pneumoniae ( S. pneumoniae) is recovered from sputum of patients with chronic obstructive pulmonary disease (COPD) during stable disease and exacerbations. In patients with community acquired pneumonia, antibiotic exposure in the prior 3–6 months is associated with recovery of antibiotic resistant isolates of S. pneumoniae. Whether the same relationship is seen in COPD is not known. From April 1994 to June 2004, 127 adults with COPD were enrolled in a prospective longitudinal study. Sputum isolates of S. pneumoniae were characterized with susceptibility testing and pulsed-field gel electrophoresis (PFGE). The relationship between antibiotic use in the previous 3 and 6 months with either new acquisition of a resistant pneumococcal isolate or development of resistance (4-fold increase in MIC) in a pre-existing colonizing pneumococcal strain was determined. A total of 194 pneumococcal isolates were recovered from 38 patients. Among 71 newly acquired and 4 resistance-emergent strains analyzed further, rates of resistance to penicillin (MIC ≥2), erythromycin (MIC ≥1), tetracycline (MIC ≥8) and trimethoprim/sulfamethoxazole (MIC ≥4) were 8%, 24%, 17% and 16% respectively. Flouroquinolone resistance was not seen. Among strains isolated from patients exposed to a macrolide within 6 months, 53.6% displayed erythromycin resistance vs. 14% of strains without such exposure ( p = 0.00085). Similar associations were not seen for other antibiotics. Macrolide use in the previous 6 months is associated with macrolide resistance in sputum isolates of S. pneumoniae. Recent antibiotic exposure may help in determining appropriate antibiotic treatment in these patients. [ABSTRACT FROM AUTHOR]

Abstract: A new class of chimeric molecules have been developed. These are based on polyphenols like catechin and epicatechin and monocyclic β-lactams. The two units are joined via a triazole linker using the ‘Click Chemistry’ conditions. The compounds showed good to weak antibacterial activity against Escherichia coli as well as moderate inhibition of RNase A. [Copyright &y& Elsevier]

Background In patients who were clinically diagnosed as having beta lactam allergy and had negative skin tests, the rates of reported resensitization to beta lactams after subsequent exposures, vary significantly. Some allergists advocate skin testing before every exposure to beta lactams. Objective We sought to determine the true rate of beta lactam allergy and of resensitization in children with a positive history for suspected beta lactam allergy. Methods The study was conducted from July 1998 to May 2004, with follow-up during 2007. Beta lactam allergy tests with the major determinant and freshly prepared minor determinant mixtures were offered to history positive children. Negative skin tests were followed by oral challenge. The tests were performed again 1–5 months later in order to address the possibility of resensitization. Results Tests were performed on 166 children: 150 for penicillins alone, 14 for penicillin in combination with cephalosporins, and an additional 2 patients solely for cephalosporins. Only 10 children (6%) were positive in the initial evaluation, four by skin test and six by oral challenge. A second set of tests was performed in 98 children with a negative initial evaluation; only two children (2%) were resensitized. On a follow-up survey of 71 of the 96 patients, 59 (83%) had received beta lactams; only one had developed a minor rash after subsequent exposure to amoxicillin. Conclusions Most children with suspected beta lactam allergy were not allergic to beta lactams. Resensitization to beta lactam antibiotics in children in this study was infrequent. In children with a clinical diagnosis of beta lactam allergy and negative skin tests, repeated skin testing before every exposure is usually unnecessary. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) proteins Tat and gp120 have been implicated in the pathogenesis of HIV dementia by various mechanisms, including down-regulation of excitatory amino acid transporter-2 (EAAT2), which is responsible for inactivation of synaptic glutamate. Recent work indicates that beta-lactam antibiotics are potent stimulators of EAAT2 expression. The authors treated mixed human fetal neuronal cultures with recombinant gp120 or Tat, in the presence or absence of ceftriaxone, and determined neurotoxicity by measuring mitochondrial membrane potential and neuronal cell death. Ceftriaxone produced dose-dependent attenuation of the neurotoxicity and neuronal cell death caused by both viral proteins. This study demonstrates that this class of drugs may have therapeutic efficacy in HIV dementia. [ABSTRACT FROM AUTHOR]

Background: The effects of ethnicity on beta lactam allergy have not been reported. The Negev Desert in Southern Israel is inhabited by two ethnically distinct populations: Jews and Bedouin Muslims. Approximately 60% of the pediatric population of the area is Jewish. Whereas most Jews live in Westernized urban centers, Bedouins are in the process of transition from semi-nomadic conditions to a sedentary lifestyle and the majority of them now live in towns and villages. We sought to determine the rate and characteristics of physician-reported beta lactam allergy in Jewish and Bedouin children. Methods: The medical records of all children registered in five primary community clinics were reviewed and screened for allergy to beta lactam antibiotics. Results: A total of 26 655 medical records were reviewed: of 11 069 Jewish children and 15 586 Bedouin children. Beta lactam allergy was registered in 344 records (1.3%), and was more frequent in Jewish ( n= 226, 2.1%) than in Bedouin children ( n= 118, 0.8%, P < 0.0001). Beta lactam allergy was more common in boys in both populations ( P < 0.01). The clinical features of the reaction that led to the diagnosis of beta lactam allergy were not significantly different between the two ethnic populations, although the specific antibiotics prescribed and the diagnoses for which they were prescribed were different in the two ethnic populations. Conclusions: We concluded in this study that pediatric beta lactam allergy was registered more frequently in Jewish than in Bedouin children, and in boys more than in girls. [ABSTRACT FROM AUTHOR]