Carbapenem Group Research Articles

Investigation of virulence factor genes and biofilm formation of antibiotic resistant clinical E.coli isolates.

The aim of this study is to investigate the antibiotic sensitivity, presence of virulence genes and biofilm formation capacity of 90 clinical E. coli isolates. The presence of virulence genes in E.coli isolates were investigated by PCR. Ninety clinical isolates of E.coli were subjected to biofilm quantitative analysis using the semi-quantitative crystal violet staining method. it was observed that the isolates were resistant to quinolone, cephalosporin, aminoglycoside, carbapenem and penicillin group antibiotics. The presence of virulence factor genes were observed in a total of 86/90E. coli. The highest rate of fim (92.2%) virulence factor gene was detected in the strains. Afa, pap, cnf, sfa, hly were detected in 30%, 13%, 13%, 3.3%, 2.2% respectively. Also, 13 different virulence factor gene patterns were determined in 90E. coli isolates. Of the 90E. coli isolates whose biofilm-forming capacities were evaluated, 42 were found to have biofilm-forming capacity. Of these 26 (28.8%) the weak, 12 (13.3%) moderate and 4 (4.4%) strong biofilm-forming. Also, statistical analysis was performed to investigate the relationship between virulence factor genes and biofilm formation, and none of the 7 genes analyzed showed a significant relationship with biofilm formation. since pathogenic E. coli is an important public health problem, investigating antibiotic resistance, virulence factor genes and biofilm formation in bacterial pathogens is important for better treatment options.

Multidrug resistant (MDR) and extensively drug-resistant (XDR) gram negative bacteria at a tertiary care hospital, in Lalitpur, Nepal

Introduction: Prevalence of multi and extensively drug resistant (MDR and XDR) gram negative bacteria (GNB) are increasing trend and becoming a threat to public health. There is no single effective antibiotic to treat these pathogens. These superbugs need continuous surveillance to develop relevant treatment protocols and early therapeutic approaches. In this study, we evaluated the trends in prevalence, etiology and antibiogram of MDR and XDR GNB isolated from various samples in a tertiary care hospital. Method: It was a hospital based descriptive cross-sectional study conducted at Patan Hospital, Patan Academy of Health Sciences. All the records of the patient whose culture and sensitivity report yielded gram negative bacteria from 1st January 2021 to 31st December of 2023 was extracted from the hospital electronic database and analyzed. Ethical approval was taken from the institutional review committee. Result: The prevalence of MDR GNB was found to be at 22.30%. The prevalence of XDR GNB among the total isolated GNB was 9.41%. Acinetobacter baumanii complex, Klebsiella spp., Escherichia coli and Pseudomonas aeruginosa were the most common MDR and XDR pathogens encountered. For the antibiotics tested, a higher number of isolates were susceptible to carbapenem group (32%) followed by aminoglycosides (28.3%) doxycycline (26%) and piperacillin-tazobactam (17.4%). Conclusion: More than 22% of patients with GNB infection were multidrug resistant. Aminoglycosides and carbapenems are good options for treatment of MDR-GNB infection however treatment should be based on culture and sensitivity reports. When treating XDR-GNB infection, adding doxycycline can also be considered.

Multidrug Resistance Gram-negative Bacteria in Intensive Care Unit of Tertiary Care Hospital: A Descriptive Cross-sectional Study

Introduction: Antimicrobial resistance is global health problem, amongst major causes for mortality. It is one of the hinderance for achievement of Sustainable Goal 3 (Good health and well-being) of WHO. Multidrug resistant gram negative bacteria are major threat to humanity especially patients admitted in intensive care unit. This is associated with to treatment failure and mortality of the patients in intensive care unit. Therefore, this study was conducted to find out the prevalence of Multidrug resistant gram negative bacteria in intensive care unit of tertiary care center. Methods: A descriptive cross-sectional study was conducted in the Department of Microbiology of a tertiary care hospital from February, 2020 till August, 2021 for 18 months after obtaining ethical approval from the Institutional Review Committee (Reference Number: 246). All the samples from Intensive Care Unit were processed following standard methodology. Only Gram-negative bacteria isolated from samples were included in the study. Convenience sampling method was used. The point estimated was calculated at 95% Confidence Interval. Data was entered in Microsoft Excel 2016 and analysis was done using IBM SPSS Statistics version 16.0.Results: Out of 500 samples only 380 showed growth of gram negative bacteria. The prevalence Multi Drug Resistance was 83.15%. The prevalence of multidrug resistant was notably higher among Acinetobacter spp (100%) followed by Non fermenter (95%) and Escherichia coli (87.1%). Multidrug resistant isolates were least resistant towards carbapenem group of antibiotics.Conclusions: The prevalence of Multidrug resistant gram negative bacteria was found to be lower than in the study conducted in similar setting.

Prevalence of Microorganisms in UTI and Antibiotic Sensitivity Pattern among Gram Negative Isolates: A Cohort Study

Urinary tract infections (UTI) are the second most important infections followed by Respiratory tract infections. It is also important to observe the prevalence of organisms for the appropriate use of antibiotics. The study identifies Pseudomonas species and E.coli as the most predominant organisms among 180 samples. The sensitivity pattern was observed according to CLSI guidelines 2021 and most of them beta-lactam inhibitors. It is also observed that 100% of the isolates were sensitive to carbapenem and uriedopencillin group of drugs.

The Association Between Antibiotic Resistance and Biofilm Production in Klebsiella pneumoniae Isolated from Urinary Tract Infections.

Background and aims This research investigates the link between biofilm formation and antibiotic resistance among Klebsiella pneumoniae bacteria in Sana'a city, Yemen, a common cause of hospital-acquired infections and community-acquired infections. Methods: A 6-month study investigated 300 urinary tract infections samples, with 241 culture-positive. Standard methods were used for isolation and identification, including biofilm production and antibiogram susceptibility patterns of Klebsiella pneumoniae. Results: The study reveals that penicillin resistance is linked to Klebsiella pneumoniae's ability to form biofilms. Ampicillin-resistant isolates formed biofilms 97.5% of the time, while non-biofilm-producing isolates had a lower rate of resistance. Carbapenem group resistance was also significant, with Meropenem-resistant isolates forming biofilms 42.5% of the time. Cephalosporin resistance ranged from 80-95% for Biofilm-Forming Isolates, while Quinolones resistance ranged from 65-82%. Aminoglycoside resistance was also significant, with gentamicin and amikacin resistance rates being 42.5% and 42.5%, respectively. These findings highlight the importance of understanding the phenotypes of Klebsiella pneumoniae in forming biofilms. Conclusion: The study found a strong correlation between the biofilm production of Klebsiella pneumoniae and antibiotic resistance, with quinolones and cephalosporins being the least active, while carbapenems and aminoglycosides showed slight sensitivity.

No improvement in mortality among critically ill patients with carbapenems as initial empirical therapy and more detection of multi-drug resistant pathogens associated with longer use: a post hoc analysis of a prospective cohort study.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

Hepatotoxicity and Its Impact on Mortality in COVID-19 Patients

Objective: "COVID-19-related liver damage" can occur frequently in course of COVID-19 disease and cause significant problems. Our study aimed to investigate prevalence of liver damage due to COVID-19, its risk variables, and the effect of liver damage on course of COVID-19 and mortality. Method: One hundred patients over eighteen years of age who were hospitalized between 01.08.2021-01.03.2022 and had positive RT-PCR tests were included in our study. Impaired liver function tests were identified as having alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels exceeding upper laboratory limits. Results: The mean age of patients included in study was 57.9 ± 14.9 years, with 49% of them being male. In our study, we had an 8% death rate and 37% of patients had abnormal liver function tests. The presence of severe disease(p&lt;0.001), anorexia symptoms(p=0.027), and abdominal pain(p=0.010) were significant for mortality. A prolonged hospital stay was significantly associated with death(p=0.029), with the mean length of hospital stay being 11.8 ± 4.6 days. Favipiravir use for longer than five days was associated with a substantial risk of liver damage(p=0.044) and mortality(p=0.020), while use of antibiotics in carbapenem group was associated with a significant risk of death(p=0.001). Conclusions: It is noteworthy that a considerable proportion of COVID-19 patients may exhibit increased liver tests, which could serve as a significant predictor and risk factor, particularly with regard to mortality. In order to properly monitor and manage COVID-19 patients, particularly those who are at risk, comprehensive measurements, including liver tests, should be carried out on a regular basis.

Non-carbapenem Drugs for Patients with Bacteremia caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Piperacillin-Tazobactam

Background/Aims: Carbapenems are recommended for treating bacteremia caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E). However, this has resulted in a significant rise in the utilization of carbapenems in cases of ESBL-E infection. We evaluated the clinical outcomes of patients with ESBL-E bacteremia treated with non-carbapenem antimicrobials.Methods: We conducted a retrospective case-control study of a cohort of patients with documented ESBL-E bacteremia from January 2021 to December 2021. The patients were divided into two groups according to whether they received non-carbapenem or carbapenem therapy. The rates of treatment failure, 30-day mortality and microbiologic failure, and the durations of hospitalization and of antimicrobial therapy were compared between the two groups. Antimicrobial susceptibility testing and phenotypic identification of ESBL-E were performed using the Vitek 2 system.Results: Of 118 patients with ESBL-E bacteremia, 54 received non-carbapenem drugs (non-carbapenem group [NCG]) and 64 received carbapenems (carbapenem group [CG]). Treatment failure at 30 days occurred in 16.7% of the patients in the NCG and in 18.8% in the CG (p = 0.65). The 30-day mortality rate was 14.8% in the NCG and 17.2% in the CG (p = 0.63). Extra-urinary tract infection and prior antimicrobial therapy within 30 days were risk factors for treatment failure in patients with ESBL-E bacteremia. The clinical outcomes did not differ significantly between the two groups, challenging the prevailing preference for carbapenems in the treatment of ESBL-E bacteremia.Conclusions: Non-carbapenem antimicrobials such as piperacillin/tazobactam are recommended for patients with mild ESBL-E bacteremia in South Korea.

The role of microbes and parasites in recurrent pyogenic cholangitis.

Recurrent pyogenic cholangitis (RPC) and ascariasis are prevalent in eastern India. Exact pathogenesis of RPC is still a matter of controversy. Hepatobiliary Ascaris infestation has been considered one of the causative factors in Eastern Asia, but conclusive evidence from India is lacking. RPC is associated with multi-drug-resistant (MDR) bacteria, which is a significant source of morbidity and mortality. This study aimed to assess the role of hepatobiliary ascariasis in pathogenesis of RPC and to study microbial profile and their implications in managing RPC patients. Consecutive patients with biliary stones who underwent surgery between March 2020 and December 2021 in a tertiary centre in eastern India were divided into RPC and non-RPC groups. Surgically retrieved samples of bile and biliary stones were sent for bacterial culture and microscopic and histopathological examination to identify the evidence of ascariasis in both groups and to study the microbial profile in RPC group. Eight out of 54 patients (14.8%) in the RPC group had evidence of hepatobiliary ascariasis. None of the patients in non-RPC group showed evidence of ascariasis. Klebsiella was the most common bacterial pathogen on bile culture, and 79% of bacterial isolates were MDR pathogens. Carbapenem group of antibiotics showed the highest sensitivity (66.6%) against bacterial culture growth in RPC patients. This study showed a higher prevalence of hepatobiliary ascariasis in patients with RPC, but a conclusive etiological role is still lacking. RPC is associated with high incidence of MDR bacteria. Carbapenems may be considered the empirical antibiotic of choice in RPC.

Combination of photodynamic therapy with antibiotic therapy - future or misalliance?

SignificanceThe growing antibiotic resistance of microorganisms is an increasingly important challenge for modern medicine. In the next few decades, the so-called post antibiotic era is likely to begin. For this reason, the search for new solutions using PACT seems particularly promising. ApproachFour new chlorin compounds were tested and photochemically characterized for singlet oxygen generation efficiency and photostability. They have been evaluated for bactericidal properties against MRSA, E. coli (ESBL+) and C. albicans. Their synergism with antibiotics from the group of cephalosporins and carbapenems was evaluated. ResultsA reduction of approximately 3 logs or more was achieved for each of the bacterial strains. A decrease in MIC values was observed for all bacteria, the greatest for ceftriaxone. ConclusionsCombining traditional antibiotic therapy with PACT may be a promising route in the case of antibiotic-resistant infections, but requires further in-depth research.

Demonstration of Interaction between Carbapenem Group Antibiotics and Different Immunosuppressant Drugs by Molecular Docking

Background: It has been shown that drugs used parenterally cause errors in immunosuppressant concentrations measured by LC-MS / MS method. It is yet unknown whether this measurement error is due to drug-drug interaction or analytical interference. Objective: The aim of this study is to investigate the possible interaction and inhibition concentrations of broad-spectrum antibiotics (ertapenem, meropenem, imipenem) with 4 different immunosuppressants (tacrolimus, sirolimus, everolimus, cyclosporine A) by molecular docking. Method: The docking results of ertapenem, meropenem, and imipenem-cilastatin drugs, which are frequently used in intensive care units and wards, were analyzed with the Autodock 4.2 program. Binding energy levels and inhibition concentrations were recorded. Results: The highest binding energies of the most stable conformations, providing the best compatibility among the active ingredients, belong to cilastatin. The interaction energy of cilastatin with sirolimus in 320 conformations was calculated as -4.08 kcal/mol. Sirolimus interacted with ertapenem at -3.43, imipenem at -2.53, and meropenem at -3.84 kcal/mol. According to these values, the receptor, which is the most compatible host with all ligand molecules, is sirolimus. The least interaction energy value was calculated between cyclosporine and imipenem (-1.12 kcal / mol). Conclusion: Concerning the most stable conformations of models docked with Autodock tools, it has been determined that carbapenems interact with immunosuppressants. Since the detected inhibition concentration levels can be seen in blood samples taken immediately after carbapenem injection, immunosuppressant measurement is recommended before the use of carbapenem in immunosuppressant monitoring of transplant patients.

Стратегия эффективного административного контроля антимикробной терапии в отделении реанимации и интенсивной терапии хирургического профиля: ретроспективное пилотное исследование.

Objective: To evaluate a strategy for effective administrative control of targeted antimicrobial therapy in surgical intensive care unit (ICU) patients. Materials and methods. The study included 3522 patients who were treated in ICU No. 1 in the period 2022 to 2023. The first group (control), treatment period 2022, included 1764 patients. The second group (research), treatment period 2023, included 1758 patients. In both groups, the use of antimicrobial drugs (AMP) was carried out in accordance with the antibacterial therapy control strategy (ASCT); in group 2, systemic administrative control was additionally carried out in the form of the use of the “Effective Hospital” program and a developed analytical system with monitoring the financial stability of the unit, aimed at daily monitoring of operating activities. A comparative analysis of the frequency of use of various classes of antimicrobial agents, the incidence of infectious complications, mortality rates and financial costs between groups was performed. Results. There was a significant decrease in the consumption of AMPs of the carbapenem group from 8194 vials in 2022 to 6577 vials in 2023, which was a decrease of 19.7%; a decrease in the consumption of tetracycline group AMPs in 2023 compared to 2022, from 2338 bottles to 1581 bottles, which amounted to 32.4%; reduction in the consumption of vancomycin and linezolid in 2023 compared to 2022 from 562 vials to 313 vials, which amounted to 44.3%. There was a decrease in the incidence of VAP from 59.3 (57.6; 62.9) in 2022 to 48.1 (38.65; 61.9) units in 2023, which amounted to 10.8% (p = 0.053). The increase in the frequency of deaths from 10.9% (9.1; 12.4) in 2022 to 11.5% (10.5; 12.7) in 2023 did not have significant differences (p = 0.67). The total expenditure on AMP in 2023 significantly decreased by 22.3%, which allowed saving 1,477,205.53 rubles (p = 0.012). Conclusion. The use of a daily strategy of administrative control of operational activities and the use of antimicrobial therapy in the ICU can reduce the costs of expensive antimicrobial agents, reduce the incidence of nosocomial infectious and inflammatory complications without changing overall mortality.

The prevalence of antibiotic resistance genes of carbopenemases of the metallo-β-lactamase group in enterobacteria strains isolated from patients of a multidisciplinary hospital in a region with a developed petrochemical industry

The research work included strains of Klebsiella pneumonaie (n = 128) isolated from patients of a multidisciplinary hospital in a large industrial city. The antibiotic sensitivity of the isolated pure cultures was studied in relation to the most popular antibacterial drugs in clinical practice (in the amount of 21), by the standard disco-diffusion method. Identification of resistance genes was carried out by PCR using commercial reagent kits «AmpliSens MDR-MBL-FL», «AmpliSens MDR-KPC/OXA-48‑FL». The results of determining the sensitivity of isolates isolated from the lower respiratory tract revealed low activity of amoxicillin/clavulanic acid, cephalosparins of the III and IV generation (ceftazidim, cefotaxime, cefepim). 86.7 % of isolates are resistant to the aminoglycoside group — amikacin, and 100 % are resistant to gentamicin. Meropenem was the most active of the carbapenem group — 26.6 %, about 7 % are sensitive to ertapenem. From the group of fluoroquinolones, the sensitivity varied from 20 to 30 %. The greatest activity of all drugs was shown by ticarcillin / clavulanate — 33.3 %. A high proportion of strains of Kl. pneumoniae with a phenotype of multiple resistance has been established. The identification of resistance genes made it possible to establish their diversity in antibiotic-resistant isolates, a high proportion (26.6 %) of multi-resistant strains with the absence of the studied genes, and the combination of VIM + NDM + OXA-48 genes, identified in every second studied strain, prevails. Thus, the analysis of the prevalence of antibiotic resistance genes of carbopenemases of the metallo- β-lactamase group in enterobacteria strains isolated from patients of a multidisciplinary hospital in a region with a developed petrochemical industry showed the predominance of isolates (53.9 %) with the production of a combination of three antibiotic resistance genes (VIM + NDM + OXA-48). Isolates containing two genes simultaneously (NDM + OXA-48 and VIM + OXA-48) identified in 7.8 and 6.3 %. Isolates containing a single gene (carbapenemase Kl. Pneumoniae) amounted to 5.4 %.

Decrease in the effectiveness of valproic acid against the background of antibacterial therapy with imipenem/cilastatin in pediatric practice: A case report

A clinical case of the co-medication of valproic acid and cilastatin/imipenem in a 17-year-old girl with generalized tonic-clonic seizures is described. As an antiepileptic therapy, the child was prescribed valproic acid, the concentration of which in the blood plasma was more than 80 µg/ml, and seizures were not observed during this therapy. At the same time, due to the developed pneumonia, the girl was imipenem/cilastatin prescribed. Co-medication of drugs led to a decrease in the concentration of valproic acid in the blood plasma less than 50 µg/ ml, relapse of epileptic seizures was noted. Correction of antiepileptic therapy with phenobarbital did not lead to the seizure control. The removal of imipenem/ cilastatin contributed to the increase in the concentration of valproic acid in blood plasma above 50 µg/ ml, which corresponds to the recommended therapeutic range. Within two weeks after discontinuation of imipenem/ cilastatin, the concentration of valproic acid reached values as close as possible to the values before the start of antibiotic therapy. The authors of the article concluded that it is necessary to conduct therapeutic drug monitoring in children receiving valproic acid and imipenem/ cilastatin (antibiotic of carbapenem group), based on the known mechanisms of pharmacokinetic interaction.

Molecular identification and characterization and phylogenetic study in Escherichia coli in Baghdad province

The study involved a total of 112 Escherichia coli isolates that were obtained from diverse origins. It took place within the jurisdiction of Baghdad Province. The isolates were classified into distinct phylogenetic groups using Quadruplex Clermont's innovative methodology. Phylogenetic typing was determined using the multiplex PCR technique. The findings of the present investigation reveal that the phylogenetic group B2 exhibited the highest prevalence rate (34.8%), followed by phylogenetic groups C (21.4%), D (16.9%), and A (10.7%). The remaining groups, namely B1 (5.3%), E (4.4%), F (2.6%), and unknown (3.5%), exhibited comparatively lower prevalence rates. Furthermore, the present study has identified a significant correlation between cephalosporins and phylogenetic groupings of E. coli. The cephalosporin groups were found to be associated with a significant proportion of antibiotic resistance patterns, whereas the carbapenem groups exhibited the lowest association. The biofilm formation was detected in 78.5% (88/112) of the isolates, and 95.5% (107/112) of the strains exhibited multiresistance. The group B2 exhibited the highest prevalence of antibiotic resistance and biofilm formation, with a percentage of 33.6% (36/107) and 35% (31/88).

Effectiveness of empiric carbapenem versus non-carbapenem therapy for extended-spectrum β-lactamase producing Enterobacterales infections in non-intensive care unit patients: a real-world investigation in a hospital with high-prevalence of extended-spectrum β-lactamase producing Enterobacterales.

To investigate whether empiric carbapenem therapy, compared to empiric non-carbapenem therapy, was associated with improved clinical outcomes among hospitalized, non-intensive care unit (ICU) patients with extended-spectrum β-lactamase (ESBL)-producing Enterobacterales infections. We performed a retrospective cohort study of adult, non-ICU patients admitted with ESBL-producing Enterobacterales infections. Primary outcome was time to clinical stability from the first empiric antibiotic dose. Secondary outcomes were early clinical response and 30-day all-cause hospital readmission. We used multivariate regression methods to examine time to clinical stability. Of the 142 patients, 59 (42%) received empiric carbapenems and 83 (58%) received empiric non-carbapenems, most commonly ceftriaxone (49/83, 59%). Median age was 59 years. The most common infection source was urinary (71%). The carbapenem group had a higher proportion of patients who received antibiotics within 6 months of admission (55% vs 28%, P < .01) and history of ESBL (57% vs 17%, P < .01). There were no significant differences in hours until clinical stability between the carbapenem and non-carbapenem groups (22 (IQR: 0, 85) vs 19 (IQR: 0, 69), P = .54). Early clinical response (88% vs 90%, P = .79) and 30-day all-cause hospital readmission (17% vs 8%, P = .13) were similar between groups. Among hospitalized non-ICU patients with ESBL-producing Enterobacterales infection, we found no difference in time to clinical stability after the first empiric antibiotic dose between those receiving carbapenems and those who did not. Our data suggest that empiric carbapenem use may not be an important driver of clinical response in patients with less severe ESBL-producing Enterobacterales infection.

Effect of Empirical Antimicrobial Therapy of Piperacillin-tazobactam Versus Carbapenems on Mortality for Patients with Sepsis from Nursing Homes.

Background Nursing home residents with a high risk of multidrug-resistant organism infection pose a complex challenge to broad-spectrum empirical antimicrobial therapy, particularly those infected with extended-spectrum β-lactamase-producing Enterobacteriaceae. The present study compared the efficacy of piperacillin-tazobactam and carbapenems as empirical antimicrobial treatments for patients with sepsis from nursing homes. Patients and Methods Using a nationwide inpatient database in Japan, we identified patients diagnosed with sepsis within two days of admission from nursing homes between 2018 and 2021. We selected patients who received intravenous piperacillin-tazobactam or carbapenems within two days of admission. In-hospital mortality was compared between the piperacillin-tazobactam and carbapenem groups using inverse probability of treatment weighting. Result We identified 8,025 eligible patients. Of these, 3,391 (42%) received piperacillin-tazobactam, and 4,634 (58%) received carbapenems within 2 days of admission. The inverse probability of treatment weighting analysis showed no significant difference in in-hospital mortality between the groups (31.6% in the piperacillin-tazobactam group and 32.8% in the carbapenem group; risk difference, 1.2%; 95% confidence interval, -3.2% to 0.9%). Conclusions Carbapenems and piperacillin-tazobactam as empirical antimicrobial therapy in patients with sepsis from nursing homes were associated with comparable in-hospital mortality rates. These findings highlight the importance of making decisions regarding broad-spectrum empirical antimicrobial therapy.

Genetic Evaluation of Heteroresistance among Carbapenem‐Susceptible Clinical Isolates of Enterobacterales

Carbapenems currently serve as the last line of defense when treating serious infections caused by multidrug‐resistant Enterobacterales species; however, heteroresistance of these species is thought to cause failure in the treatment with these broad‐spectrum antibiotics. This study was designed to determine the prevalence of carbapenem heteroresistance and associated genotypic modifications among phenotypically meropenem‐susceptible Escherichia coli and Klebsiella pneumoniae isolates. A total of 204 isolates of E. coli (n: 118) and K. pneumoniae (n: 86) from various clinical samples were included in this prospective experimental study. Identification and antimicrobial susceptibility testing of the isolates were performed by VITEK® (bioMérieux, France). Strains that were found susceptible to carbapenem group antibiotics (meropenem, imipenem, and ertapenem) with automated system were further investigated by disk diffusion method. The isolates with discrete colony growth within the clear inhibition zone among phenotypically meropenem‐susceptible strains were tested for heteroresistance with the “gold standard” population analysis profile‐area under the curve (PAP‐AUC) method. In addition, heteroresistant isolates were analyzed for the presence of carbapenemase genes with in‐house PCR method. The heteroresistance prevalence rate was 3.5% for E. coli and 18.1% for K. pneumoniae. The presence of heteroresistance in a total of 10 meropenem‐susceptible isolates (E. coli, n: 4; K. pneumoniae, n: 6) was confirmed by the PAP‐AUC method. The most frequently detected carbapenemase in heteroresistant isolates was OXA‐48 (6/10), followed by NDM‐1 (2/10). Meropenem is frequently preferred as initial empirical monotherapy in most of Gram‐negative infections in adult and pediatric patients. The presence of heteroresistance against meropenem is too important to ignore, and for this reason, it seems beneficial to prefer combined treatment regimens in clinical practice.

Efficacy of noncarbapenem therapy for the treatment of ceftriaxone-resistant Enterobacterales outside the urinary tract.

To determine the safety of noncarbapenem versus carbapenem antibiotics for treatment of adults with documented infection caused by ceftriaxone-resistant infections outside the urinary tract. Retrospective cohort of adult patients with a documented infection caused by an extended-spectrum β-lactamase (ESBL)-producing organism isolated between January 2018 and October 2021. An academic tertiary-care center. Adult patients with a documented infection caused by an ESBL-producing organism outside the urinary tract. The primary outcome was a composite of treatment failure defined as 30-day mortality, 30-day readmission, microbiological recurrence, and/or clinical worsening requiring antibiotic change. Secondary outcomes included differentiation of primary composite components and postantibiotic Clostridioides difficile infection (CDI). This study included 130 patients. The primary source of infections were bloodstream (67.7%) and caused by Escherichia coli (81.5%). Overall, 101 patients received carbapenem therapy and 29 received noncarbapenem therapy (NCT). NCT was comprised of mainly fluoroquinolones (18 of 29) followed by cefepime (7 of 29). Patients receiving NCT had shorter hospital stays (median, 7 days vs 9 days) and were more often discharged on antibiotics (79.3% vs 50.5%). We did not detect a significant difference in the primary composite outcome of treatment failure for carbapenem (23.8%) versus noncarbapenem treatment (24.2%; P = .967). Secondary outcomes included a numerically higher 30-day mortality rate in the noncarbapenem group compared to the carbapenem group: 4 (13.8%) of 29 versus 4 (3.9%) of 101. We did not detect a difference in rates of CDI. Noncarbapenem therapy may play a role for certain patients with infections caused by ESBL-producing organisms.

Detection of Carbapenemase Producing Gram-negative Bacteria at a Tertiary Care Hospital: A Cross-sectional Study

Introduction: Gram-negative bacteria have developed a broad spectrum of resistance due to antibiotic degradation enzymes, including Extended-spectrum Beta-lactamases (ESBL), AmpC β-lactamases, and carbapenemases. Carbapenemase- producing organisms, such as Escherichia coli, Klebsiella species, Acinetobacter species, and Pseudomonas species, have become one of the most important causes of nosocomial and community-acquired infections. Aim: To identify carbapenemase-producing organisms among Multidrug-resistant (MDR) clinical isolates and detect Metallo β-Lactam Carbapenemases (MBL). Materials and Methods: The present study is a cross-sectional study that included 1266 clinical samples from patients visiting the Department of Microbiology, Ranagaraya Medical College, Kakinada, Andhra Pradesh, India. from July 2022 to December 2022. The samples were processed using the standard culture and antimicrobial susceptibility test, employing the Kirby-Bauer Disk Diffusion method. The present study included organisms that were resistant to either imipenem or meropenem. Carbapenemases were detected using the Modified Hodge test (MHT), and MBL carbapenemases were detected using the Imipenem Ethylene Diamine Tetraacetic acid (EDTA) Double Disk Test (DDT) following the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Descriptive statistics were performed on the collected data. Results: The study samples comprised 842 (66.5%) Gram- negative isolates and 424 (33.5%) Gram-positive isolates. Among the Gram-negative isolates, 80 (9.5%) were carbapenem- resistant, of which MHT showed 56 (70%) positive isolates (carbapenemase-producing) and 24 (30%) negative isolates. Imipenem-EDTA DDT showed 50 (62.5%) positive isolates (MBL-producing) and 30 (37.5%) negative isolates. Conclusion: Carbapenemase production in Gram-negative organisms has reduced the clinical utility of the carbapenem group of drugs, posing a major challenge in the treatment of severe infections. In summary, the majority of carbapenem-resistant isolates in the present study were from the Enterobacteriaceae family. These isolates were subjected carbapenem-resistant isolates to MHT and DDT tests to identify carbapenemase and metallo-beta-lactamase-producing strains that were resistant to a wide spectrum of antibiotics. The present study enables the early detection of these MDR strains, ensuring appropriate management.