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

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

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

Background: Avibactam, relebactam and vaborbactam are β-lactamase inhibitors that proved their efficiency against KPC-producing Enterobacterales. Regarding their inhibitor activity towards Ambler's class A extended spectrum β-lactamases (ESBL) and Ambler's class C cephalosporinase (AmpC), they should be active on most of the carbapenem-resistant non-carbapenemase-producing Enterobacterales (CR non-CPE). Objectives: Determine the in vitro activity of ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam and comparators against CR non-CPE. Methods: MICs to ceftazidime/avibactam, imipenem/relebactam, meropenem/vaborbactam, but also temocillin, ceftolozane/tazobactam, ertapenem, colistin, eravacycline and tigecycline were determined by broth microdilution (ThermoFisher) on a collection of 284 CR non-CPE (inhibition zone diameter < 22 mm to meropenem). Whole genome sequencing was performed on 90 isolates to assess the genetic diversity as well as resistome. Results: According to EUCAST breakpoints, susceptibility rates of ceftazidime, imipenem, meropenem and ertapenem used at standard dose were 0.7%, 45.1%, 14.8% and 2.5%, respectively. Increased exposure of ceftazidime, imipenem and meropenem led to reach 3.5%, 68.3% and 67.7% susceptibility, respectively. Using the EUCAST clinical breakpoints, susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam were 88.4%, 81.0% and 80.6%, respectively. Susceptibility rates of temocillin, ceftolozane/tazobactam, tigecycline, eravacycline, and colistin were 0%, 4.6%, 27.8%, 54.9% and 90.1%. MICs distributions with and without the presence of the inhibitor demonstrated a better ability of avibactam and relebactam compared to vaborbactam to restore susceptibility to the associated β-lactam. Conclusions: This study demonstrated the in vitro efficacy of ceftazidime/avibactam, imipenem/relebactam and to a lesser extent meropenem/vaborbactam against CR non-CPE. Moreover, to test all β-lactams/β-lactamases inhibitors combinations without a priori for CRE, non-CPE is crucial since resistance to one of the β-lactam/β-lactamase inhibitor combinations does not predict resistance to another molecule, depending on the resistance mechanisms involved. [ABSTRACT FROM AUTHOR]

Abstract Background Carbapenem-induced neurotoxicity is an unusual side effect, with seizure being the most commonly reported symptom. Among the carbapenems, imipenem-cilastin is classically associated with the most severe neurotoxicity side effects. Carbapenem is mainly excreted by the kidney and its half-life is significantly increased in patients with chronic kidney disease (CKD). Therefore, dose adjustment is necessary in such patients. Ertapenem-associated neurotoxicity is increasingly being reported in CKD patients, but rarely seen in patients with recommended dose adjustment. Case presentation We report a case of a 56-year-old male patient with chronic kidney disease 5 on dialysis(CKD 5D). The patient presented with a history of fever, chills and rigours during a session of haemodialysis (HD). He was diagnosed with Enterobacter cloacae catheter-related blood stream infection and was started on ertapenem. After 13 days of ertapenem, he experienced an acute confusional state and progressed to having auditory and visual hallucinations. His blood investigations and imaging results revealed no other alternative diagnosis. Hence a diagnosis of ertapenem-induced neurotoxicity was made. He had complete resolution of symptoms after 10 days’ discontinuation of ertapenem. Conclusion Our case draws attention to the risk of potentially serious toxicity of the central nervous system in HD patients who receive the current recommended dose of ertapenem. It also highlights that renal dosing in CKD 5D patients’ needs to be clinically studied to ensure antibiotic safety.

The systematic review titled "Efficacy and Safety of Carbapenem Antibiotics in Hidradenitis Suppurativa" explores the use of carbapenem antibiotics in treating the chronic inflammatory skin disorder, Hidradenitis Suppurativa (HS). The study included 181 patients with HS who received carbapenem treatment, primarily ertapenem, showing clinical improvement and pain reduction. Minor adverse events were reported, and consolidation therapy post-carbapenem treatment was beneficial in maintaining clinical improvement. The review suggests the potential utility of carbapenems in treating recalcitrant HS, but highlights the need for further large-scale clinical trials to optimize treatment strategies. [Extracted from the article]

[Display omitted] Antimicrobial resistance is a significant public health issue. In addressing the threat of multidrug resistant bacterial infections, carbapenems have been used. The carbapenem-resistant Enterobacterales (CRE) are, however, rapidly expanding worldwide. Since the issue of CRE is also a problem in Saudi Arabia, the current meta-analysis was performed to comprehensively evaluate the resistance rates to the main carbapenem antibiotics and determine the actual prevalence of CRE in the country. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was followed. Different web databases including PubMed, Scopus, Web of Science, and ScienceDirect were searched for relevant records. Data were extracted, and summary estimates for resistance to carbapenems were calculated using DerSimonian-Laird method of meta-analysis and the random-effects model. From a total of 787 retrieved records, 69 studies were found fully eligible and were included in the final analyses. More than 50 % of all the studies were conducted after 2010, and the most frequently examined members of the Enterobacterales were Escherichia coli and Klebsiella pneumoniae. The pooled prevalence estimate for imipenem resistance was 6.6 % (95 % CI: 4.7–9.2), 9.1 % (95 % CI: 6.7–12.3) for meropenem, and 18.6 % (95 % CI: 11.9–27.9) for ertapenem. High heterogeneity (I2 > 97 %, p < 0.001) was observed for all the estimates. Compared to other regions of the country, there was higher resistance rates in the Al-Qassim and Al-Jouf provinces. Additionally, resistance to ertapenem was as high as 34.2 % in the most recent study period (2021–2024). Proteus spp was the most prevalent CRE (26.2 %). This review highlights an increasing rate of carbapenem resistance among Enterobacterales , emphasizing the need for collaborative efforts to implement strict infection control and prevention measures. Consistent surveillance is indispensable for safeguarding public health, guiding clinical decisions, and strengthening efforts to tackle the challenges of antibiotic resistance. [ABSTRACT FROM AUTHOR]

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

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

MALDI-TOF mass spectrometry has become widely used in clinical microbiology and has proved highly accurate for detection of carbapenemases in Gram-negative bacteria. However, the use of carbapenem-hydrolysis assays in routine diagnostics is hampered by the need for antibiotic substances and for making their fresh solutions each time an assay is conducted. Here, we evaluated the use of commercial antibiotic susceptibility-testing disks as source of ertapenem substrate in MALDI-TOF MS-based assay for detection of carbapenemase-producing Enterobacterales (CPE). The assay was validated on 48 CPE isolates of 8 different species expressing NDM-, VIM-, KPC- and OXA-48-type carbapenemases and exhibiting various levels of resistance to carbapenems (MIC range: 0.25-> 32 mg/l), as well as on 48 carbapenemasenon-producing isolates. The assay conditions were optimized as follows: 10-μl loopful of bacterial colonies was suspended in 150 μl 0.01 M Na-PBS buffer, pH 7.4, a 10 μg ertapenem susceptibility-testing disk was immersed in the suspension and incubated 3 h at 35°C, after which supernatant was obtained by centrifugation and applied on a target plate with alpha-cyano-4-hydroxycinnamic acid matrix. Mass spectra were analyzed between 440 and 560 m/z. Carbapenemase activity was detected in all tested CPE isolates by the appearance of m/z peaks corresponding to ertapenem hydrolysis products: [Mh + H]+:494.2, [Mh + Na]+:516.2, [Mh + 2Na]+:538.2, [Mh/d + H]+:450.2, [Mh/d + Na]+:472.2, and simultaneous decrease or loss of peaks of intact antibiotic: [M + H]+:476.2, [M + Na]+:498.1, [M + 2Na]+:520.1. No hydrolysis peaks or loss of intact ertapenem peaks were observed for carbapenemase-negative strains. We therefore report the development of a sensitive, specific and costeffective MALDI-TOF MS-based assay for detection of CPE, which makes use of antibiotic disks readily available in most laboratories. [ABSTRACT FROM AUTHOR]

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

The aim of the study was to determine the efficacy of carbapenem-only combination treatments derived from four approved drugs (meropenem, doripenem, ertapenem and imipenem) against a MDR strain of P. aeruginosa in a Galleria mellonella larvae infection model. G. mellonella larvae were infected with P. aeruginosa NCTC 13437 (carrying the VIM 10 carbapenamase) and the efficacy of the six possible dual, four triple, and one quadruple carbapenem combination(s) were compared to their constituent monotherapies. Four of these combinations showed significantly enhanced survival compared to monotherapies and reduced the bacterial burden inside infected larvae but without complete elimination. Bacteria that survived combination therapy were slower growing, less virulent but with unchanged carbapenem MICs—observations that are consistent with a persister phenotype. In vitro time-kill assays confirmed that the combinations were bactericidal and confirmed that a low number of bacteria survived exposure. Mass spectrometry was used to quantify changes in the concentration of carbapenems in the presence of carbapenemase-carrying P. aeruginosa. The rate of degradation of individual carbapenems was altered, and often significantly reduced, when the drugs were in combinations compared with the drugs alone. These differences may account for the enhanced inhibitory effects of the combinations against carbapenem-resistant P. aeruginosa and are consistent with a 'shielding' hypothesis. In conclusion, carbapenem combinations show promise in combating MDR P. aeruginosa and are worthy of additional study and development. [ABSTRACT FROM AUTHOR]

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

Diarrhea is one of the leading causes of morbidity and mortality in developing countries. Diarrheagenic Escherichia coli (DEC) is an important bacterial agent for diarrhea in infants, children, and international travelers, and accounts for more than 30% of diarrheal cases in children less than 5 years old. However, the choices of antimicrobial agents are now being limited by the ineffectiveness of many first-line drugs, in relation to the emergence of antimicrobial-resistant E. coli strains. The aim of this systematic review and meta-analysis was to provide an updated prevalence of antimicrobial-resistant DEC in Asia. A comprehensive systematic search was conducted on three electronic databases (PubMed, ScienceDirect, and Scopus), where 40 eligible studies published between 2010 and 2022 were identified. Using meta-analysis of proportions and a random-effects model, the pooled prevalence of DEC in Asian diarrheal patients was 22.8% (95% CI: 16.5–29.2). The overall prevalence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing DEC strains was estimated to be 66.3% (95% CI: 58.9–73.7) and 48.6% (95% CI: 35.1–62.1), respectively. Considering antimicrobial drugs for DEC, the resistance prevalence was highest for the penicillin class of antibiotics, where 80.9% of the DEC isolates were resistant to amoxicillin and 73.5% were resistant to ampicillin. In contrast, resistance to carbapenems such as imipenem (0.1%), ertapenem (2.6%), and meropenem (7.9%) was the lowest. The relatively high prevalence estimation signifies that the multidrug-resistant DEC is a public health threat. Effective antibiotic treatment strategies, which may lead to better outcomes for the control of E. coli infections in Asia, are necessary. [ABSTRACT FROM AUTHOR]

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Secondary peritonitis with intra-abdominal abscesses (IAA) is difficult to treat because of the supposed low rate of penetration of antimicrobial drugs at the site of infection. However, clinical data about the actual bioavailability of antimicrobial drugs in IAA are scarce. This prospective observational study aimed at assessing the drug penetration in IAA of the antibiotics (piperacillin-tazobactam, carbapenems) and antifungals (fluconazole, echinocandins) that are usually recommended for the treatment of intra-abdominal infections. Patients with IAA who underwent a radiological or surgical drainage procedure were included. Antimicrobial drug concentrations were measured in IAA (C IAA ) and in a simultaneous plasma sample (C plasma ) to assess the C IAA /C plasma ratio. The pharmacodynamic target was defined as a C IAA equal or superior to the clinical breakpoints of susceptibility of the most relevant intra-abdominal pathogens. Clinical outcomes were assessed at hospital discharge. A total of 54 antimicrobial drug measurements were performed in 39 IAA samples originating from 36 patients. Despite important inter-individual variability, piperacillin-tazobactam exhibited the highest C IAA /C plasma ratios (median 2). The rates of target achievement were 75%-80% for piperacillin-tazobactam and meropenem but 0% for imipenem and ertapenem. These results tended to correlate with clinical outcomes (96% success rate versus 73%, respectively, P = 0.07). Among antifungals, fluconazole exhibited higher C IAA /C plasma ratios and rates of target achievement compared to echinocandins. However, no differences in clinical outcomes were observed. These results provide unique information about antimicrobial drug penetration in IAA in real clinical conditions and suggest that piperacillin-tazobactam and meropenem may have better efficacy compared to imipenem or ertapenem.

Purpose: To investigate the effect of pre-biopsy rectal swab and urine screening combined with a risk-adapted antibiotic treatment strategy on reducing post-biopsy infections (PBIs) following multiparametric magnetic resonance imaging (mpMRI)/ transrectal ultrasound (TRUS) fusion-targeted transrectal prostate biopsy (TRPBx)., Methods: 1119 Patients undergoing mpMRI-TRUS fusion TRPBx between June 2017 and February 2024 were included. Patients were screened for rectal extended-spectrum beta-lactamase (ESBL)/multi-resistant gram-negative (MRGN) and urinary pathogens. Standard-risk patients (rectal non-ESBL/MRGN-carriers) either received Cefuroxime (2017-2020) or Ceftriaxone (2020-2024) intravenously before biopsy. For high-risk patients (rectal ESBL/MRGN-carriers) intravenous Ertapenem was used. Patients with positive urine cultures received oral targeted prophylaxis. PBIs were the primary outcome of the study. We used uni- and multivariable logistic regression analysis (MLRA) to reveal predictors for the main outcome., Results: Rectal ESBL/MRGN prevalence was 5.5%. For standard-risk patients, PBI-rates were 8.1% and 0.24% for Cefuroxime and Ceftriaxone (p < 0.0001), respectively. Only 1.7% of high-risk patients treated with Ertapenem developed PBI. On MLRA, Cefuroxime (OR 38.7, 95%-CI: 10.9-246), oral Ciprofloxacin (OR 103, 95%-CI: 10.8-994), other oral targeted antibiotics (OR 42.7, 95%-CI: 1.86-496) (reference Ceftriaxone, all p < 0.005) were significant predictors for PBI whereas Ertapenem (OR 7.30 95%-CI: 0.34-77.4, p = 0.11) was not., Conclusion: By integrating rectal swab ESBL/MRGN and urine screening, we developed a tailored antibiotic treatment strategy, resulting in low PBI-rates following TRPBx. Carbapenem-based treatment of high-risk patients is crucial. Ceftriaxone should be considered for routine use in standard-risk patients as it offers very low PBI-rates., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the local ethics committee (Medical University Innsbruck); identifier: 1262/2022. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains ( P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups ( P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.

In the present study, we determine the synergistic activity of ertapenem with cefazolin and flucloxacillin against type A beta-lactamase producing Methicillin susceptible Staphylococcus aureus isolate. In the time kill assay, at standard inoculum, ertapenem with cefazolin showed >1 log kill and ertapenem with flucloxacillin demonstrated >2 log kill. When tested at high inoculum, both combinations achieved >1 log kill at 1x MIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background Salmonella Typhi ( S. Typhi) is increasingly resistant to multiple antibiotics, posing a challenge in treatment, particularly in multidrug-resistant (MDR) cases. Carbapenems, including doripenem, ertapenem, and meropenem, have been considered last-resort options. This study evaluates the effectiveness of these carbapenems against S. Typhi isolates in a clinical setting in Peshawar, Pakistan. Objective To assess the effectiveness of the carbapenem antibiotics, doripenem, ertapenem, and meropenem, against S. Typhi. Methods This study collected data from blood cultures of patients diagnosed with S. Typhi infections at the Hayatabad Medical Complex in Peshawar, Pakistan for two years: from January 1, 2022, to December 31, 2023. Sensitivity testing was performed using the disk diffusion method in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. The analysis examined the sensitivity rates of the three antibiotics and compared their effectiveness. Results A total of 626 S. Typhi isolates were tested. Only 11.98% of the isolates were sensitive to doripenem, while 88.02% were resistant to it. In contrast, 35.5% of the isolates responded to ertapenem, with 64.5% being resistant. Meropenem showed the highest efficacy, with 42.7% of the isolates demonstrating sensitivity. These findings highlight the growing challenge of managing multidrug-resistant (MDR) S. Typhi infections, especially in regions where resistance to carbapenems is becoming prevalent. Conclusion Meropenem proved to be more effective against S. Typhi compared to doripenem and ertapenem. The study emphasizes the need for ongoing monitoring of resistance patterns and the exploration of alternative or combination treatment options. These findings have immediate clinical implications for empiric therapy choices and highlight the urgent need for antibiotic stewardship programs in endemic regions., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Medical Teaching Institution (MTI), Hayatabad Medical Complex, Peshawar, Pakistan issued approval 2222, dated December 8, 2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Background: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin among guidelines. However, there is variability among guidelines for maximal ST NICs of cephalosporins., Objective: To determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants., Methods: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 6 increasing concentrations of 1 or more β-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm compared with negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted., Results: A total of 747 participants with a median age of 64 (interquartile range: 54-72) years (52% male, 85% White, and 92% non-Hispanic) underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/mL): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely nonirritant close to or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data., Conclusions: Our results suggest that SPTs with undiluted stock β-lactam antibiotic concentrations are nonirritant. Compared with previously published nonirritant concentrations, we propose a 2- to 50-fold increase to the maximal IDT and dIDT NICs of 15 β-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Wen-Qi Xu,1,2 Xiao-li Zheng,1,2 Jing-Wei Liu,1,2 Qian Zhou,1,2 Xiao-Yu Zhu,1,2 Jin Zhang,1,2 Yan Han,1,2 Kai Chen,1,2 Shao-Chun Chen,1,2 Xiang-Sheng Chen,1,2 Yue-Ping Yin1,2 1STD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2STD Reference Laboratory, National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Yue-Ping YinSTD Reference Laboratory, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of ChinaTel/Fax +86 258 547 8024Email yinyp@ncstdlc.orgPurpose: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018.Methods: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected.Results: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤ 0.008 mg/L to 0.5 mg/L. The corresponding MIC50 and MIC90 were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥ 0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P < 0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = − 0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥ 0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥ 0.25 mg/L for ertapenem.Conclusion: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.Keywords: Neisseria gonorrhoeae, treatment, ertapenem, antimicrobial resistance

Ertapenem is a member of carbapenem antibiotics used for the treatment of moderate-to-severe intra-abdominal, urinary tract, acute pelvic, and post-surgical gynecologic infections. The antibacterial activity of ertapenem is mediated through binding to penicillin-binding proteins which results in inhibiting the cross-linking of the peptidoglycan layer of the bacterial cell wall. Therefore, ertapenem can be labeled with technetium-99m (99mTc), a gamma emitter radionuclide, for the diagnosis of deep-seated bacterial infections, such as urinary tract, intra-abdominal, osteomyelitis, and post-surgical gynecologic infections. The labeling procedure was carried out by varying the reaction conditions, such as the amount of the ligand and reducing agent, pH, reaction time and temperature, and radioactivity. At optimized reaction conditions more than 93% 99mTc–ertapenem radioconjugate was obtained. 99mTc–ertapenem was found 90% intact in saline medium up to 6 h, while 88% intact in human blood serum up to 3 h. Biodistribution study showed target-to-non-target ratios of 2.91 ± 0.19, 2.39 ± 0.31, and 1.23 ± 0.22 in S. aureus, E. coli, and turpentine oil-infected rat models, respectively. The SPECT scintigraphy showed high uptake of 99mTc–ertapenem in bacterial-infected abscesses, and low counts were recorded in normal and turpentine oil-inflamed tissues. In conclusion, 99mTc–ertapenem can be a potent infection-imaging agent, which can diagnosis deep-seated bacterial infections at early stage but need further pre-clinical evaluation in variety of infection models.

ObjectivesTo assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem.MethodsThe following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found.ResultsFifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with β-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99–1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97–1.20) between ertapenem and other carbapenems. Compared with β-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71–1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31–1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59–4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events.ConclusionOur findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.

Objectives: To characterize one OXA-232-producing wzi93-KL112-O1 carbapenem-resistant Klebsiella pneumoniae (CRKP) co-harboring chromosomal blaCTX-M-15 and one rmpA2-associated virulence plasmid. Methods: Minimum inhibitory concentrations (MICs) were measured via broth microdilution method. Conjugation, chemical transformation, string test and Galleria mellonella infection model experiments were also conducted. Wholegenome sequencing (WGS) was performed on the Illumina and Nanopore platforms. Antimicrobial resistance determinants were identified using ABRicate program with ResFinder database. Insertion sequences (ISs) were identified using ISfinder. Bacterial virulence factors were identified using virulence factor database (VFDB). Wzi, capsular polysaccharide (KL) and lipoolygosaccharide (OCL) were analyzed using Kleborate with Kaptive. Phylogenetic analysis of 109 ST15 K. pneumoniae strains was performed using core genome multilocus sequence typing (cgMLST) on the Ridom SeqSphere+ server. MLST, replicons type, SNP strategies and another cgMLST analysis for 45 OXA-232-producing K. pneumoniae strains were further conducted using BacWGSTdb server. Results: K. pneumoniae KPTCM strain belongs to ST15 with wzi93, KL112 and O1. It possessed a multidrug-resistant (MDR) profile and was resistant to carbapenems (meropenem and ertapenem), ciprofloxacin and amikacin. Virulence assays demonstrated KPTCM strain possesses a low virulence phenotype. WGS revealed it contained one circular chromosome and nine plasmids. The carbapenemase-encoding gene blaOXA-232 was located in a 6141-bp ColKP3-type non-conjugative plasmid and flanked by DISEcp1 and DlysR-DereA. Interestingly, blaCTX-M-15 was located in the chromosome mediated by ISEcp1-based transposon Tn2012. Importantly, it harbored a rmpA2-associated pLVPK-like virulence plasmid with iutA-iucABCD gene cluster and one IS26-mediated MDR fusion plasmid according to 8-bp (AGCTGCAC or GGCCTTTG) target site duplications (TSD). Based on the cgMLST and SNP analysis, data showed OXA-232-producing ST15 K. pneumoniae isolates were mainly isolated from China and have evolved in recent years. Conclusions: Early detection of CRKP strains carrying chromosomal blaCTX-M-15, OXA-232 carbapenemase and pLVPK-like virulence plasmid is recommended to avoid the extensive spread of this high-risk clone. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae of sequence type (ST) 11 is a hyper-epidemic nosocomial clone, which is spreading worldwide among humans and emerging in pets. This is the first report, to the best of our knowledge, of multidrug-resistant (MDR) K. pneumoniae ST11 carrying blaSCO-1 and blaDHA-1, isolated from a four-month-old dog in Belgium. Antimicrobial susceptibility testing (AST) of the isolate, performed via broth microdilution following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, revealed resistance to eight different classes of antimicrobials, including carbapenems, in particular ertapenem, third-generation cephalosporins and fluoroquinolones. A hybrid approach, combining long- and short-read sequencing, was employed for in silico plasmid characterization, multi-locus sequence typing (MLST) and the identification and localization of antimicrobial resistance (AMR) and virulence-associated genes. Three plasmids were reconstructed from the whole-genome sequence (WGS) data: the conjugative IncFIB(K), the non-mobilizable IncR and the mobilizable but unconjugative ColRNAI. The IncFIB(K) plasmid carried the blaSCO-1 gene, whereas IncR carried blaDHA-1, both alongside several other antimicrobial resistance genes (ARGs). No virulence genes could be detected. Here, we suggest that the resistance to ertapenem associated with susceptibility to imipenem and meropenem in K. pneumoniae could be related to the presence of blaSCO-1 and blaDHA-1, combined with permeability defects caused by point mutations in an outer membrane porin (OmpK37). The presence of the blaSCO-1 gene on a conjugative IncFIB(K) plasmid is worrisome as it can increase the risk of transmission to humans, to animals and to the environment. [ABSTRACT FROM AUTHOR]

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

The global emergence and spread of genes responsible for the production of ESBL (extended-spectrum beta-lactamases) and carbapenemases in Klebsiella pneumoniae isolates poses a serious threat to public health. The aim of this study was to retrospectively analyze the frequency of occurrence and drug resistance of selected alarm agents isolated from patients of the specialist hospital in Wrocław. A total of 13,528 clinical materials collected from patients of a specialist hospital in Wrocław were analyzed in the period from 1 January 2020 to 31 December 2020. Overall, 3894 bacterial strains were isolated from clinical materials, including 416 K. pneumoniae isolates. K. pneumoniae that showed resistance to ETP (ertapenem) and/or MEM (meropenem) were tested using phenotypic tests for the detection of KPC (carbapenemase-producing Klebsiella), MBL (metallo-β-lactamase) and OXA-48 (oxacilinase-48) carbapenemases. In the case of a positive or doubtful result of the phenotypic test, immunochromatographic tests and the CarbaNP test were performed. In total, 58 K. pneumoniae isolates resistant to 1 or more carbapenem antibiotics were isolated. Of the 58 strains, 16 (27.6%) were isolated from rectal swabs conducted on CPE (carbapenemase-producing Enterobacteriaceae) carriers. In the case of CRE (carbapenem-resistant Enterobacteriaceae) K. pneumoniae, carbapenemases were detected in 28/58 (48.3%) isolates. Notably, 23/28 K. pneumoniae isolates produced MBL/NDM (New Delhi metallo-β-lactamase) (82.1%), 5/28 produced VIM (Verona-intergon-encoded metallo-β-lactamase) (14.3%), and one produced MBL/NDM + OXA-48. Carbapenemases were detected in 13 of 16 (81.3%) carbapenem-resistant K. pneumoniae isolates derived from rectal swabs. The significant participation of CRE and CPE isolates in the infections proves the need to test patients admitted to hospital wards for their status as a CPE carrier in order to limit the emergence of new epidemic outbreaks. [ABSTRACT FROM AUTHOR]

The aim of this work is to identify and count antimicrobial resistance (AMR) in hospital effluents (HEs) of 2 units of the University Hospital Mohamed VI the Mother and Child Hospital (MCH) and the Ar-razi Surgical Hospital (ArzH), and to compare the two hospital units in terms of ARMs and seasonal variation. Each HE was sampled during 2016 and 2017. After identification of the pathogenic strains and determination of AMR, the results were reported for 24 ABs, including 3 carbapenems (CBP), and their consumption rates. The Predicted environmental concentration (PEC) rate of carbapenems in the HE of the study sites is calculated. A comparative analysis of the AMR of the isolated bacterial species was performed and related to the evolution of PEC in HEs. In the ArzH effluents:15 strains isolated, 7 are carbanepenem-resistant Enterobacteria (CRE) and are resistant to at least one of the 3 carbapenems tested. ArzH and MCH effluents respectively show some similarities: 26.87% and 28.57% of isolated bacteria are resistant to ertapenem while 43.48% and 57.14% are resistant to meropenem. However, for imipenem, the MCH effluent has a higher percentage of bacterial antibiotic resistance than ArzH. In addition, the percentage of resistance in each hospital unit effluent is mainly in relation with the increasing antibiotic consumption and predicted environmental values PEC for very antibiotic in each unit in the same period. [ABSTRACT FROM AUTHOR]

Background: Ceftolozane/tazobactam (C/T) is a combination of an antipseudomonal oxyiminoaminothiazolyl cephalosporin with potent in vitro activity against Pseudomonas aeruginosa and tazobactam, a known β-lactamase inhibitor. The aim of this study was to evaluate the activity of C/T against clinical isolates of P. aeruginosa and Enterobacterales collected from five Latin American countries between 2016 and 2017, before its clinical use in Latin America, and to compare it with the activity of other available broad-spectrum antimicrobial agents. Methods: a total of 2760 clinical isolates (508 P. aeruginosa and 2252 Enterobacterales) were consecutively collected from 20 hospitals and susceptibility to C/T and comparator agents was tested and interpreted following the current guidelines. Results: according to the CLSI breakpoints, 68.1% (346/508) of P. aeruginosa and 83.9% (1889/2252) of Enterobacterales isolates were susceptible to C/T. Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins, piperacillin/tazobactam and carbapenems when tested against P. aeruginosa, and its performance in vitro was comparable to fosfomycin. When tested against Enterobacterales, it showed higher activity than cephalosporins and piperacillin/tazobactam, and similar activity to ertapenem. Conclusions: these results show that C/T is an active β-lactam agent against clinical isolates of P. aeruginosa and Enterobacterales. [ABSTRACT FROM AUTHOR]

Our aim was to assess whether newer carbapenems with a better administration profile than meropenem (ertapenem, faropenem and tebipenem) were more effective against Mycobacterium tuberculosis including M/XDRTB and determine if there was a synergistic/antagonistic effect with amoxicillin or clavulanate (inhibitor of beta-lactamases that MTB possesses) in vitro. Whilst meropenem is given three times a day intravenously, ertapenem, though given parenterally, is given once a day, faropenem and tebipenem are given orally. Eighty-two clinical drug-sensitive and -resistant MTB strains and a laboratory strain, H37Rv, were assessed by a microdilution methodology against ertapenem, faropenem, tebipenem and meropenem with and without amoxicillin or clavulanic acid. Ertapenem showed a limited activity. The addition of amoxicillin and clavulanate did not translate into significant improvements in susceptibility. Sixty-two isolates (75.6%) exhibited susceptibility to faropenem; the addition of amoxicillin and clavulanate further reduced the MIC in some isolates. Faropenem showed a limited activity (MIC of 8 mg/L or lower) in 21 strains completely resistant to meropenem (MIC of 16 mg/L or higher). Fifteen of the meropenem-resistant strains were susceptible to tebipenem. Carbapenems' activity has been reported extensively. However, there remains uncertainty as to which of them is most active against TB and what the testing methodology should be. [ABSTRACT FROM AUTHOR]

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

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

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

Objective. To evaluate in vitro activity of biapenem and other clinically available carbapenems against Russian clinical isolates of Enterobacterales, Pseudomonas aeruginosa и Acinetobacter spp., including isolates with acquired fermentative mechanisms of resistance to β-lactams. Materials and Methods. A total of 3139 Enterobacterales isolates, 793 P. aeruginosa isolates and 634 Acinetobacter spp. isolates from hospitalized patients in 63 hospitals from 35 Russian cities were included in the study during 2018-2019. Minimal inhibitory concentrations (MIC) for biapenem and other antimicrobials were determined in accordance with ISO 20776-1:2006. Carbapenemases genes were detected by commercially available real-time PCR kits AmpliSens® MDR KPC/OXA-48-FL and AmpliSens® MDR MBL-FL (Central Research Institute of Epidemiology, Russia). Data analysis and reporting was performed using AMRcloud online platform (www.amrcloud.net). Results. For all tested Escherichia coli isolates MIC50/90 were 0.06/0.125 mg/l for biapenem, 0.125/0.25 mg/l for imipenem, and 0.06/0.06 mg/l for meropenem. When MIC50/90 for ertapenem (0.015/0.125 mg/l for all isolates tested) were comparable to those of biapenem, a greater number of nosocomial E. coli isolates had MIC >4 mg/l for ertapenem (3.6%) than for biapenem (2.6%). MIC50/90 of Klebsiella pneumoniae for biapenem were 0.5/16 mg/l, for both imipenem and meropenem – 0.5/32 mg/l, for ertapenem – 2/32 mg/l. Resistance to oxyimino-β-lactams had no significant influence on activity of biapenem against Enterobacterales isolates. For 321 carbapenemase-producing K. pneumoniae isolates (ОХА-48 – 63.9%, NDM – 27.7%) biapenem has shown no advantages over imipenem and meropenem. МПК50/90 for nosocomial and community-acquired P. aeruginosa isolates were 8/64 mg/l and 0,5/16 mg/l for biapenem, 8/128 mg/l and 1/16 mg/l – for imipenem, 16/64 mg/l and 0,5/32 mg/l – for meropenem. All carbapenems, including biapenem, had very low in vitro activity against carbapenemaseproducing P. aeruginosa isolates. МПК50/90 of Acinetobacter spp. were 64/128 mg/l for biapenem, 64/128 mg/l – for imipenem, and 128/128 mg/l – for meropenem. Conclusions. According to the MIC distributions and MICs50/90 values independently of the presence of fermentative mechanisms of resistance to β-lactams, in vitro activity of biapenem against Russian clinical isolates of Enterobacterales, P. aeruginosa and Acinetobacter spp. was comparable to those of imipenem and meropenem.

Study objectiveRandomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy.MethodsPatients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate.ResultsOf 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/μL (range 6,200 to 23,100/μL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group.ConclusionA multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.