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Herbaspirillum spp. is a common environmental bacterium usually found in soil, plant roots, and water. It is rarely associated with infection in immunocompromised patients, and rarely reported infections in immunocompetent patients. We report the first case of a Herbaspirillum huttiense bacteraemia in a non‐neutropenic home haemodialysis patient. A 57‐year‐old male presented to our hospital with a 3‐day history of malaise, fevers, rigours, and anorexia following dialysis through his central line. On examination, he was pyrexic (temperature 38.7°C) with splinter haemorrhages noted, but no other signs of infection were present. Blood cultures revealed a polymicrobial infection, with Serratia liquefaciens and Corynebacterium jeikeium isolated from the central line and Herbaspirillum sp. was isolated from both the central line and a peripheral culture. A later peripheral blood culture following central line removal isolated Herbaspirillum huttiense. Regular biological testing of his home water supply and dialysate detected no colony forming units of non‐fermenting gram‐negative bacilli. He was initially treated with ceftriaxone and vancomycin initially, followed by ertapenem and vancomycin. Intravenous antibiotics were ceased following 5 days after central line removal and he made an uneventful recovery. [ABSTRACT FROM AUTHOR]

Background: Novel β-lactam antibiotics as well as other kinds of antibiotics have been used to treat complicated urinary tract infections (cUTIs); however, their efficacy and safety remain controversial. Objective: We conducted a systematic review with meta-analysis to explore the efficacy and safety of novel β-lactam antibiotics versus other antibiotics against cUTIs. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched systematically from inception through 15 March 2024 for clinical trials comparing novel β-lactam antibiotics with other antibiotics for treatment of cUTIs. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of clinical response, microbiologic response, adverse effects (AEs), serious adverse effects (SAEs). The quality of evidence was evaluated with the Cochrane Risk of Bias assessment tool. The review was registered in INPLASY (INPLASY202440054). Results: Ten randomized controlled trials involving 5, 925 patients met our inclusion criteria. Our meta-analysis revealed that there was no significant difference in overall clinical response (RR = 1.02), AEs (RR = 1.07), SAEs (RR = 1.20) between novel β-lactam antibiotics groups and other antibiotics groups. However, a significant difference was found in a subgroup of clinical cure rates at the end of treatment between novel β-lactam antibiotics groups and carbapenems groups, with low heterogeneity (RR = 1.02). A significant difference was observed in microbiologic response (RR = 1.11). Subgroup analysis revealed a significant difference in microbiologic response between novel BBL/BLS groups and carbapenems groups (RR = 1.13, I² = 21%, P = 0.005). Differences was observed between novel BBL/BLS groups and piperacillin/tazobactam sodium groups (RR = 1.21, I² = 70%, P = 0.02). Similar results were obtained from subgroup analysis of the difference in microbiologic response between novel β-lactam antibiotics groups and ertapenem groups (RR = 0.92, I² = 0, P = 0.01). Conclusion: Novel β-lactam antibiotics had similar overall clinical cure, AEs, SAE, to other antibiotics in the treatment of cUTIs. However, novel β-lactam antibiotics demonstrated superior clinical cure rates compared to carbapenems in a subgroup analysis, and exhibited better microbiologic response than other antibiotics. [ABSTRACT FROM AUTHOR]

We aimed to assess the accuracy of BD Phoenix for determining carbapenem susceptibility because we observed a decline in carbapenem susceptibility rate from the biannual cumulative data, after we transitioned to the BD Phoenix form Vitek 2 system. Between October 2021 and May 2022, we collected 82 non-duplicated Enterobacterales showing non-susceptible to at least one of the three carbapenems by BD Phoenix. We performed the broth microdilution (BMD) and disk diffusion (DD) according to the CLSI guideline. Compared to BMD, the categorical agreements for ertapenem (ERT), imipenem (IPM) and meropenem (MEPM) was 58.8%, 56.8% and 91.5% for BD Phoenix and it was 85.4%, 89.0%, and 97.6%, respectively, for DD (p value; 0.0001 for ERT and IPM , p value; 0.17 for MEPM). The major errors/minor errors for ERT, IPM, and MEPM were 14.0%/31.7%, 2.94%/40.7%, and 2.56%/6.10%, respectively for BD Phoenix, compared to 0%/14.6%, 0%/9.8%, and 0%/2.5%, for DD. While errors in the BD Phoenix showed tendency towards resistance, those in DD displayed no tendency towards either resistance or susceptibility. With DD, 21 out of the 27 isolates showing susceptible/intermediate/susceptible pattern (ERT/IPM/MEPM) and 13 out of the 16 isolates showing intermediate/susceptible/susceptible pattern (ERT/IPM/MEPM), were correctly categorized by DD. However, for 22 isolates showing resistant/susceptible/susceptible pattern (ERT/IPM/MEPM), only 13 isolates were correctly categorized by DD. In conclusion, to mitigate the risk of overcalling carbapenem non-susceptibility with BD Phoenix, it will be helpful to perform a complementary test using DD and to provide comments on the DD results to clinicians. [ABSTRACT FROM AUTHOR]

The current study aimed to determine the molecular mechanisms of carbapenem and colistin resistance among the clinical isolates of Klebsiella pneumoniae from hospitalized patients admitted to a university hospital in Eastern Algeria. In total, 124 non-duplicate isolates of K. pneumoniae were collected from September 2018 to April 2019. Bacterial identification was performed using MALDI-TOF MS. The presence of extended spectrum β-lactamase (ESBL) genes, carbapenemase genes, chromosomal mutation and mcr genes in colistin-resistant K. pneumoniae were evaluated by PCR. ESBLs represented a rate of 49.1% and harbored blaCTX-M, blaTEM and blaSHV genes. Concerning carbapenems, 12 strains (9.6%) were resistant to ertapenem (MIC: 1–32 μg/mL), of which one strain (0.8%) was also resistant to imipenem (MIC: 32 μg/mL). Among these strains, nine (75%) harbored blaOXA-48 gene. Seven strains (5.6%) expressed resistance to colistin (MIC: 2–32 μg/mL), of which two harbored mcr-8 and mgrB genes simultaneously. The existence of a double resistance to colistin in the same strain is new in Algeria, and this could raise concerns about the increase in levels of resistance to this antibiotic (MIC: 32 μg/mL). The mgrB gene alone was observed in five isolates (71.4%), including two strains harboring blaOXA-48. This is the first report revealing the presence of K. pneumoniae strains carrying the blaOXA-48 gene as well as a mutation in the mgrB gene. Large-scale surveillance and effective infection control measures are also urgently needed to prevent the outbreak of various carbapenem- and colistin-resistant isolates. [ABSTRACT FROM AUTHOR]

Abstract Using first-principles density functional theory (DFT), this study examines the improved chemical catalytic performance and biochemical sensing capabilities of iron (Fe) and gold (Au) nanoclusters decorated flawless γ-graphyne (GPN) as nanocarriers for the Ertapenem (EPM) antibiotic drug, in contrast to pristine γ-graphyne. The evaluation of binding energy analysis, it has been noted that perfect GPN (-0.96 eV), Au-decorated GPN (-1.852 eV), as well as Fe-decorated GPN (-1.520 eV), can be suitable candidates for drug delivery, as the binding energy falls in the physisorption to chemisorption range. There is a red shift in the ultraviolet-visible (UV-Vis) spectrum when EPM is adsorbed on the Fe- and Au-decorated GPN surfaces in comparison to the pristine substrates. Based on thermodynamic parameters, the values of Gibbs free energy changes (ΔG) and enthalpy change (ΔH) illustrate a strong interaction between EPM and the Au-decorated GPN (F: -1.130 and − 2.288 eV) in contrast to EPM with the Fe-decorated GPN carrier (I: -1.190 and − 2.210 eV), indicating that the interaction is stable and spontaneous. The Fe-decorated GPN improves the adsorption of EPM with a small binding energy, facilitated by a greater charge transfer from the substrate as an electron donor to the drug. This phenomenon results in a significant rise in dipole moment and a change in the energy gap. The results indicate that Fe-decorated GPN surface can serve as carriers for delivering the EPM drug.

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. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a prevalent condition characterized by persistent respiratory symptoms and airflow limitation. Bacterial infections may trigger COPD exacerbations, leading to more severe symptoms as well as increased morbidity and mortality rates. This study aimed to investigate the bacterial profiles and antibiotic resistance in COPD patients who had experienced exacerbation and type 2 respiratory failure at Adam Malik Central General Hospital, Medan, Indonesia. This retrospective study utilized medical records spanning from January 1, 2020, to December 1, 2022. The sample included patients aged 40--90 years who had experienced COPD exacerbation and type 2 respiratory failure. The exclusion criteria were patients who had received antibiotic therapy within 48 hours before admission, were severely immunocompromised, and had severe malignancy. The analysis results were presented in the form of means, standard deviations, and frequency distributions. Additionally, an analysis of the relationship between the categorical variables was performed using the Chi-squared test (p<0.05). The study analyzed 25 subjects with an average age of 63.6 years, primarily consisting of men (84%). It was shown that severe exacerbations were prevalent (92%), accompanied by the presence of common comorbidities including pneumonia (52%), diabetes mellitus (32%), and other non-communicable diseases (44%). Bacterial growth was observed in 76% of the subjects, predominantly involving Gram-negative bacteria (89.4%). Klebsiella pneumoniae (26.3%) and Pseudomonas aeruginosa (21.1%) were the most frequently isolated species. The antibiotic resistance patterns indicated that meropenem and amikacin had the highest resistance rates (100%). Cefepime, ertapenem, and gentamicin exhibited notable resistance rates of 66.7%, 66.7%, and 75.0%, respectively. This study highlights the high prevalence of Gram-negative bacteria and significant antibiotic resistance in COPD patients who exhibit exacerbation and type 2 respiratory failure. [ABSTRACT FROM AUTHOR]

Background Antibiotic treatment for complicated urinary tract infections (cUTI)/acute pyelonephritis (AP) is often followed by recurrent bacteriuria in the absence of clinical symptoms. To understand factors predictive of clinical and microbiologic outcomes in patients with cUTI/AP, multivariable analyses were undertaken using pooled data from a global, phase 3 cUTI study. Methods Using data from 366 tebipenem pivoxil hydrobromide– and 378 ertapenem-treated patients from the Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) infected with Enterobacterales uropathogens, multivariable analyses for dichotomous efficacy endpoints were performed using logistic regression and pharmacokinetic-pharmacodynamic relationships were evaluated. Results Urinary tract anatomical disorders and functional urinary tract or metabolic disorders were predictive of nonresponse across all efficacy endpoints assessed at test-of-cure (TOC) and late follow-up (LFU) visits, with greater impact on overall and microbiologic than clinical nonresponse. Independent variables predictive of increased probabilities of successful overall response at TOC and microbiologic response at TOC or LFU were baseline creatinine clearance >50 mL/min and baseline pathogen fluoroquinolone susceptibility. Infection with a phenotypic extended-spectrum beta-lactamase–positive Enterobacterales pathogen was predictive of reduced probabilities of success for microbiologic response at LFU and clinical response at TOC. Meaningful relationships between efficacy endpoints and plasma pharmacokinetic-pharmacodynamic indices were not identified. Conclusions Reductions of overall and microbiologic response in patients with cUTI/AP were associated with anatomical or functional urinary tract disorders, but not with the magnitude or duration of plasma antibiotic exposure. Results of these analyses serve to advance our understanding of factors predictive of outcome in patients with cUTI/AP. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections (PJIs) are devastating potential complications after arthroplasty surgery with significant therapeutic challenges. Many authors advocate for two-stage revision arthroplasty for PJI of the shoulder which includes explanation with antibiotic spacer placement. The optimal antibiotic/cement combination for PJI in the shoulder is not known. The purpose of this study is to analyze various cement and antibiotic concentrations against Coagulase negative staphylococcus species, S. epidermidis and S. lugdunensis. Five strains of coagulase negative Staph were taken from clinically documented orthopedic infections Both Simplex and Palacos cement were used to create antibiotic laden beads and mixed with either ertapenem, vancomycin, gentamicin, or a combination of ertapenem + vancomycin or ertapenem + gentamicin. The bacteria were plated on lysogeny broth agar plates and 3 beads were added per plate. Samples were analyzed for zone of inhibition at 24 hours, 72 hours, and 1 week. After 1 week, beads were transferred to new plates with bacteria and the process was repeated for 6 weeks. Results showed that ertapenem beads with both Simplex and Palacos cement showed the largest zones of inhibition for all samples. Vancomycin in Palacos cement and vancomycin in combination with ertapenem in Simplex and Palacos cement showed consistent zones of inhibition for the duration of the experiments. Ertapenem in combination with either vancomycin or gentamicin may allow for a powerful initial burst of killing followed by consistent antibiotic elution as opposed to gentamicin alone. While many premade spacers on the market are infused with gentamicin, our in vitro models demonstrate more efficacious bacterial eradication for antibiotics such as ertapenem and vancomycin specifically for certain low virulence organisms that are commonly found in PJI around the shoulder. [ABSTRACT FROM AUTHOR]

Urinary Tract Infection (UTI) is an infection caused by the growth of microorganisms in the human urinary tract. The bacteria Escherichia coli can cause UTIs. Escherichia coli is a bacterium that can become resistant to antibiotics in UTIs because it produces the Extended-Spectrum β-lactamase (ESBL) enzyme. ESBL causes high morbidity and mortality because it can make it challenging to manage infectious diseases. Research on ESBL-producing bacteria has been carried out in several hospitals in Indonesia. The difference in place and time of research causes the pattern of resistance of UTI-causing bacteria to antibiotics to be different. The samples in this study were urine specimens from patients with UTI diagnoses who were examined for culture at the microbiology laboratory of Indramayu Hospital. The sampling technique in this study is the total sampling method. The research method used is Quantitative Descriptive. Bacteria identification and Resistance tests were carried out using the Vitec 2 Compact tool. The data obtained from the research results are then collected in tables and used as a reference in the preparation of data analysis. Escherechia coli is the most common type of bacterial species, at 41%. Ampicillin is 100% resistant to all isolates, and Meropenem and Ertapenem are 100% sensitive. Penicillin MIC value for Sensitive outcomes ≤ 4; Intermediate 16; and Resistant ≥ 32. Cephalosporin group MIC value for Sensitive results ≤ 4; Intermediates 8; and Resistant ≥ 64. Carbapenem group MIC value for Sensitive ≤ 0.5; Intermediates 8; and Resistant ≥ 64. Identification of ESBL Escherichia coli bacteria is 89% ESBL positive and 11% ESBL negative. [ABSTRACT FROM AUTHOR]

Background Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking. Methods This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score. Results Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63–6.5) days. Patients who received combination therapy were younger (P  = 0.012), more likely to have endocarditis (P  = 0.034) and had longer median duration of bacteraemia (P  < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119–2.339) P  = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610–2.678), P  = 0.608]. Discussion Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy. [ABSTRACT FROM AUTHOR]

Background Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). Objectives To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. Methods Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. Results The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%–56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. Conclusions Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections. [ABSTRACT FROM AUTHOR]

Sepsis is a potentially fatal clinical condition that results from an immune imbalance in the host during an infection. It presents systemic alterations due to excessive activation of pro-inflammatory mediators that contribute to inflammation, formation of reactive species, and tissue damage. Anti-inflammatory mediators are then extensively activated to regulate this process, leading to immune exhaustion and, consequently, immunosuppression of the host. Considering the biological activities of the nutraceutical Agaricus brasiliensis (A. brasiliensis), such as immunomodulatory, antioxidant, and antitumor activities, the present study investigated the therapeutic potential of the lipid fraction of A. brasiliensis (LF) in a model of lethal sepsis in mice (Mus musculus), induced by cecal ligation and perforation (CLP). The results showed that treatment of septic animals with LF or LF associated with ertapenem (LF-Erta) reduced systemic inflammation, promoting improvement in clinical parameters and increased survival. The data show a reduction in pro-inflammatory and oxidative stress markers, regulation of the anti-inflammatory response and oxidizing agents, and increased bacterial clearance in the peritoneal cavity and liver. Thus, it can be concluded that LF as a treatment, and in conjunction with antibiotic therapy, has shown promising effects as a hepatoprotective, antioxidant, antimicrobial, and immunomodulatory agent. [ABSTRACT FROM AUTHOR]

Background: The preferred carbapenem for treatment of infections caused by extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in critically ill patients is debated. Objective: The purpose of this study was to evaluate the difference in clinical failure between ertapenem and meropenem for treatment of ESBL-E bacteremia in critically ill patients. Of concern is ertapenem use in hypoalbuminemia given the potential for higher drug clearance. Methods: This retrospective, matched cohort study compared critically ill patients treated with ertapenem or meropenem for ESBL-E bacteremia between October 2016 and August 2022. Patients were matched on age, sex, lowest albumin, and in a 1:2 ratio of ertapenem to meropenem. The primary outcome, clinical failure, was a composite of 30-day mortality, antibiotic escalation, and microbiological failure. Secondary outcomes included all-cause readmission and development of superinfection. Results: Of 54 patients, 18 received ertapenem and 36 meropenem. Most had a urinary infection source (55.6% vs 41.7%, P = 0.393). There was no difference in clinical failure (50.0% vs 38.9%, P = 0.436). Ertapenem patients had antibiotic escalation more often (33.3% vs 2.8%, P = 0.002). There was no difference in 30-day mortality (11.1% vs 27.8%, P = 0.298), microbiological failure (27.8% vs 11.1%, P = 0.142), all-cause readmission (22.2% vs 13.9%, P = 0.461), or development of superinfection (11.1% vs 13.9%, P = 1.000). Conclusion and relevance: There was no difference in clinical failure in a small, retrospective cohort of critically ill patients receiving ertapenem or meropenem for ESBL-E bacteremia. Ertapenem may be appropriate in some critically ill and hypoalbuminemic patients, though additional data are needed. [ABSTRACT FROM AUTHOR]

ABSTRACTCarbapenem-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.

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

Objectives: Eravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria. Methods: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia. Results: We found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC90:0.12 µg/mL) and tigecycline (MIC90:0.12 µg/mL), but was all resistant to ertapenem (MIC90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC90:0.5 µg/mL) as well as tigecycline (MIC90:1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC90:2.0 µg/mL) and tigecycline (MIC90:4.0 µg/mL), but lower to ertapenem (MIC90:32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608–0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species. Conclusions: Our study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections.

This study presents an enhanced fractional-order mathematical model for analyzing the dynamics of Klebsiella pneumonia infections and antibiotic resistance over time. The model incorporates fractional Caputo derivative operators and kernel, to provide a more comprehensive understanding of the complex temporal dynamics. The model consists of three groups: Susceptible (S), Infected (I), and Resistant (R) individuals, each controlled by a fractional differential equation. The model represents the interaction between infection, recovery from infection, and the possible development of antibiotic resistance in susceptible individuals. The existence, uniqueness, stability, and alignment of the model's prediction to the observed data were analyzed and buttressed with numerical simulations. The results show that imipenem has the highest efficacy compared with ertapenem and meropenem category drugs. The estimated reproduction number and reproduction coefficient illustrate the potential impact of this model in improving treatment strategies, while the memory effects highlight the advantages of fractional differentiation. The model predicts an increased possibility of antibiotic resistance despite effective treatment, suggesting a new treatment approach. [ABSTRACT FROM AUTHOR]

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

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin condition that typically develops in adults but can rarely affect adolescents and prepubertal children. In paediatric cases, topical antibiotics and antiseptic washes are first-line therapies, based on expert consensus, with more severe and/or recalcitrant cases generally needing systemic antibiotics or hormonal therapies. Biologics demonstrated efficacy in randomised controlled trials (RCTs) in adults, with adalimumab approved in patients aged 12 years and above; adult studies in interleukin inhibitors are in progress. The efficacy of biologics needs to be balanced against their cost and generally subcutaneous routes of administration. RCTs that include paediatric patients are needed in HS. [ABSTRACT FROM AUTHOR]

Spontaneous bacterial peritonitis is a frequent severe complication in cirrhotic patients with ascites. Carbapenem antibiotics are currently the treatment of choice for patients with hospital-acquired or healthcare-related infections. However, there is limited evidence available on the efficacy of ertapenem in cirrhotic patients with spontaneous bacterial peritonitis. As a result, the pharmacokynetics and pharmacodynamics of this antibiotic are still unknown. The objective of this study was to develop and validate measurement procedures based on liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine ertapenem concentrations in plasma and ascitic fluid. Samples were pretreated by acetronile protein-precipitation. Chromatographic separation is performed on a C18 reversed-phase Acquity®-UPLC®-BEHTM column (2.1 × 100 mm id, 1.7 µm) using a non-linear gradient of water/acetonitrile containing 0.1 % of formic acid at a flow rate of 0.4 mL/min. Ertapenem and its internal standard (ertapenem-D4) are detected by tandem mass spectrometry using positive electrospray ionization and multiple reaction monitoring, and using 476.2 → 346.0/432.2 as mass transition for ertapenem and 480.2 → 350.0 for its internal standard. No significant interferences or carry-over contamination were observed. Imprecisions, absolute relative bias, matrix effects and normalized recoveries were ≤14.5 %, ≤9.3 % (92.8–104.5) % and (98.8–105.8) %, respectively. Chromatographic measurement procedures were linear from (0.50–100) mg/L. The measurement procedures based on UHPLC-MS/MS developed and validated in this study could be useful in pharmacokynetic and pharmacodynamic studies in subjects with liver cirrhosis who develop spontaneous bacterial peritonitis treated with ertapenem. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

Klebsiella aerogenes is an important opportunistic pathogen with the potential to develop resistance against last-line antibiotics, such as carbapenems, limiting the treatment options. Here, we investigated the antibiotic resistance profiles of 10 K. aerogenes strains isolated from patient samples in the intensive-care unit of a Brazilian tertiary hospital using conventional PCR and a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. All isolates were completely resistant to β-lactam antibiotics, including ertapenem, imipenem, and meropenem with differencing levels of resistance to aminoglycosides, quinolones, and tigecycline also observed. Half of the strains studied were classified as multidrug-resistant. The carbapenemase-producing isolates carried many genes of interest including: β-lactams (blaNDM-1, blaKPC-2, blaTEM-1, blaCTX-M-1 group, blaOXA-1 group and blaSHVvariants in 20-80% of the strains), aminoglycoside resistance genes [aac(6')-Ib and aph(3')-VI, 70 and 80%], a fluoroquinolone resistance gene (qnrS, 80%), a sulfonamide resistance gene (sul-2, 80%) and a multidrug efflux system transporter (mdtK, 70%) while all strains carried the efflux pumps Acr (subunit A) and tolC. Moreover, we performed a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. The draft genome assembly of the CRK317 had a total length of 5,462,831 bp and a GC content of 54.8%. The chromosome was found to contain many essential genes. In silico analysis identified many genes associated with resistance phenotypes, including β-lactamases (blaOXA-9, blaTEM-1, blaNDM-1, blaCTX-M-15, blaAmpC-1, blaAmpC-2), the bleomycin resistance gene (bleMBL), an erythromycin resistance methylase (ermC), aminoglycoside-modifying enzymes [aac(6')-Ib, aadA/ant(3")-Ia, aph(3')-VI], a sulfonamide resistance enzyme (sul-2), a chloramphenicol acetyltransferase (catA-like), a plasmidmediated quinolone resistance protein (qnrS1), a glutathione transferase (fosA), PEtN transferases (eptA, eptB) and a glycosyltransferase (arnT). We also detected 22 genomic islands, eight families of insertion sequences, two putative integrative and conjugative elements with a type IV secretion system, and eight prophage regions. This suggests the significant involvement of these genetic structures in the dissemination of antibiotic resistance. The results of our study show that the emergence of carbapenemase-producing K. aerogenes, coharboring blaKPC-2 and blaNDM-1, is a worrying phenomenon which highlights the importance of developing strategies to detect, prevent, and control the spread of these microorganisms. [ABSTRACT FROM AUTHOR]

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

Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term "non-carbapenemase (NCP)", particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Gram-negative bacteria (GNB) account for about 70% of infections in the intensive care unit (ICU) setting and are associated with significant morbidity and mortality. In recent years, pan-drug resistant (PDR) strains, strains that are not susceptible to any antibiotic, have been emerged and new treatment strategies are required. Results: Fifty eligible patients were recruited in the three groups. A statistically significant reduction in the Sequential Organ Failure Assessment (SOFA) score was observed in the control group on day 4 in comparison to day 0 of VAP (p = 0.005). The Clinical Pulmonary Infection Score (CPIS) was also reduced on day 4 (p = 0.0016) and day 7 in comparison to day 0 (p = 0.001). Patients that received combination therapy, CAZ–AVI + ATM and DCT, presented with a lower SOFA score and CPIS on day 7 in comparison to day 0 (p = 0.0288 and p = 0.037, respectively). No differences in the ΔSOFA score and ΔCPIS were found between the groups. The control group presented with a significantly lower ICU stay and duration of mechanical ventilation (p = 0.03 and p = 0.02, respectively). There was no difference in mortality. Materials and methods: This is a retrospective analysis. This study was conducted in a mixed ICU in the University Hospital of Larissa, Thessaly, Greece during a three-year period (2020-2022). Patients suffering from ventilator associated pneumonia (VAP) due to carbapenem-resistant K. pneumonia (CR-KP) were divided in three different groups: the first one was treated using ceftazidime–avibactam plus aztreonam (CAZ–AVI + ATM group), the second was treated using double carbapenems (DCT group), and the last one (control group) received appropriate therapy since the strain was susceptible in vitro to at least to one antibiotic. Conclusions: Treatment with CAZ–AVI +ATM or DCT may offer a clinical benefit in patients suffering with infections due to PDR K. pneumoniae. Larger studies are required to confirm our findings. [ABSTRACT FROM AUTHOR]

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

Spontaneous bacterial peritonitis is a frequent severe complication in cirrhotic patients with ascites. Carbapenem antibiotics are currently the treatment of choice for patients with hospital-acquired or healthcare-related infections. However, there is limited evidence available on the efficacy of ertapenem in cirrhotic patients with spontaneous bacterial peritonitis. As a result, the pharmacokynetics and pharmacodynamics of this antibiotic are still unknown. The objective of this study was to develop and validate measurement procedures based on liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine ertapenem concentrations in plasma and ascitic fluid.

La peritonitis bacteriana espontánea es una complicación frecuente y grave de los pacientes cirróticos con ascitis. Actualmente, los antibióticos carbapenémicos son el tratamiento de elección en pacientes con peritonitis nosocomiales o relacionadas con el sistema sanitario. Pese a ello, los estudios de eficacia del ertapenem en pacientes cirróticos con peritonitis bacteriana espontánea son limitados y la farmacocinética y farmacodinamia de este antibiótico continúa siendo desconocida. Así, el objetivo de este estudio es desarrollar y validar procedimientos de medida basados en la cromatografía líquida de alta y rápida eficacia acoplada a la espectrometría de masas en tándem (UHPLC-MS/MS) para medir las concentraciones de ertapenem en el plasma y en el líquido ascítico.

Ertapenem, a carbapenem-type beta-lactam antibiotic, demonstrates broad-spectrum efficacy against a wide range of Gram-positive and Gram-negative bacteria, including aerobes and anaerobes. Importantly, it demonstrates resistance to virtually all beta-lactamases, including the extended spectrum beta-lactamases (ESBLs). Haematologic complications such as thrombocytosis, haemolysis, anaemia, and neutropenia are infrequent side effects associated with this drug. In this report, we present a rare case of ertapenem-induced thrombocytosis in a 62-year-old female patient who was admitted for a complicated urinary tract infection caused by Escherichia coli.

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

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

Cutibacterium acnes is the most common cause of prosthetic shoulder infection. Treatment often requires the placement of an antibiotic-loaded cement spacer. The exact combination of antibiotic and cement that best targets this organism is not fully understood. In this study, we performed an in vitro investigation of various antibiotic combinations in Simplex and Palacos cement to determine their efficacy against three C acnes strains. We hypothesized that gentamicin alone would underperform other antibiotics including vancomycin and ertapenem against C acnes in an in vitro environment. Additionally, we hypothesized that Palacos cement would outperform Simplex cement. Strains were cultured and antibiotic cement beads were plated in six combinations. Zones of inhibition (mm) were measured, and beads were transferred to a new culture plate at 7-day intervals. This procedure was carried out for 81 days. Mixed model for longitudinal repeated measures for continuous data was used to determine the antibiotic combination that produced the most robust zone of inhibition over time. For vancomycin, gentamicin, and vancomycin + gentamicin, these data demonstrated that for two strains, Palacos cement with vancomycin and gentamicin produced the most robust zone of inhibition over time (P <.0001, P <.0001, respectively). For one strain, Palacos cement combined with vancomycin alone produced the most robust response (P <.0001). The second highest response for this strain was seen in Palacos cement combined with vancomycin and gentamicin. Ertapenem induced the largest response among all antibiotics that we tested against all 3 strains, but its effect was short-lived (one week or less) compared to vancomycin or vancomycin with gentamicin (35-81 days). Gentamicin response in both cement combinations against C acnes was weak and lasted at most 14 days. These data suggest that Palacos cement likely offers a better elution profile than Simplex in in vitro C acnes -related prosthetic shoulder infection strains. Vancomycin and gentamicin in combination demonstrated the most prolonged response for eradication of the 3 C acnes strains tested. Additionally, ertapenem may be a promising option as it showed a short-lived but robust clearing response. Gentamicin weakly inhibits C acnes growth calling into question its use in premade spacers. [ABSTRACT FROM AUTHOR]

Background: The application of enhanced recovery after surgery principles decreases postoperative complications (POCs), length of stay (LOS), and readmissions. Pharmacoprophylaxis decreases morbidity, but the effect of specific regimens on clinical outcomes is unclear. Methods and Materials: Records of 476 randomly selected adult patients who underwent elective colorectal surgeries (ECRS) at 10 US hospitals were abstracted. Primary outcomes were surgical site infection (SSI), venous thromboembolism (VTE), postoperative nausea and vomiting (PONV), pain, and ileus rates. Secondary outcomes included LOS and 7- and 30-day readmission rates. Results: POC rates were SSI (3.4%), VTE (1.5%), PONV (47.9%), pain (58.1%), and ileus (16.1%). Cefazolin 2 g/metronidazole 500 mg and ertapenem 1 g were associated with the shortest LOS; cefotetan 2 g and cefoxitin 2 g with the longest LOS. No SSI occurred with ertapenem and cefotetan. More Caucasians than Blacks received oral antibiotics before intravenous antibiotics without impact. Enoxaparin 40 mg subcutaneously daily was the most common inpatient and discharge VTE prophylaxis. All in-hospital VTEs occurred with unfractionated heparin. Most received rescue rather than around-the-clock antiemetics. Scopolamine patches, spinal opioids, and IV lidocaine continuous infusion were associated with lower PONV. Transversus abdominis plane block with long-acting local anesthetics, celecoxib, non-anesthetic ketamine bolus, ketorolac IV, lidocaine IV, and pregabalin were associated with lower in-hospital pain severity rates. Gabapentinoids and alvimopan were associated with lower ileus rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches were associated with shorter LOS. Conclusions: Significant differences in pharmacotherapy regimens that may improve primary and secondary outcomes in ECRS were identified. In adult ECRS, cefotetan or ertapenem may be better regimens for preventing in-hospital SSI, while ertapenem or C/M may lead to shorter LOS. The value of OA to prevent SSI was not demonstrated. Inpatient enoxaparin, compared to UFH, may reduce VTE rates with a similar LOS. A minority of patients had a documented PONV risk assessment, and a majority used as-needed rather than around-the-clock strategies. Preoperative scopolamine patches continued postoperatively may lower PONV and PDNV severity and shorter LOS. Alvimopan may reduce ileus and shorten LOS. Anesthesia that includes TAP block, ketorolac IV, and pregabalin use may lead to reduced pain rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches may shorten LOS. Given the challenges of pain management and the incidence of PONV/PDNV found in this study, additional studies should be conducted to determine optimal opioid-free anesthesia and the benefit of newer antiemetics on patient outcomes. Moreover, future research should identify latent pharmacotherapy variables that impact patient outcomes, correlate pertinent laboratory results, and examine the impact of order or care sets used for ECRS at study hospitals. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

Chunjiang Wang,1 Yulu Zhou,2 Ya Zhou,3 Chao Ye4 1Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410028, People’s Republic of China; 3Department of Pharmacy, People’s Hospital of Ningxiang City Affiliated to Hunan University of Chinese Medicine, Changsha, Hunan, 410600, People’s Republic of China; 4Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, 410015, People’s Republic of ChinaCorrespondence: Chao Ye, Department of Pharmacy, The Third Hospital of Changsha, No. 176, Laodong West Road, Tianxin District, Changsha, Hunan, 410015, People’s Republic of China, Email yechao1234256@163.comBackground: Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity.Methods: Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts.Results: A total of 66 patients were included, with a median age of 71.5 years (range 40– 92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1– 14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin < 3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1– 42) after intervention including antiepileptic administration, or hemodialysis.Conclusion: Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.Keywords: ertapenem, carbapenem, neurotoxicity, encephalopathy, seizures