Diagnostic Accuracy of Hospital Antibiograms in Predicting the Risk of Antimicrobial Resistance in Enterobacteriaceae Isolates: A Nationwide Multicenter Evaluation at the Veterans Health Administration.

BACKGROUND: Many clinical guidelines recommend that clinicians use antibiograms to inform empiric antimicrobial therapy. However, hospital antibiograms are typically generated by crude aggregation of microbiologic data, and little is known about an antibiogram's reliability in predicting antimicrobial resistance (AMR) risk at the patient-level. We aimed to assess the diagnostic accuracy of antibiograms as a tool for selecting empiric therapy for Escherichia coli and Klebsiella spp. for individual patients. METHODS: We retrospectively generated hospital antibiograms for the nationwide Veterans Health Administration (VHA) facilities from 2000 to 2019 using all clinical culture specimens positive for E. coli and Klebsiella spp., then assessed the diagnostic accuracy of an antibiogram to predict resistance for isolates in the following calendar year using logistic regression models and predefined 5-step interpretation thresholds. RESULTS: Among 127 VHA facilities, 1 484 038 isolates from 704 779 patients for E. coli and 671 035 isolates from 340 504 patients for Klebsiella spp. were available for analysis. For E. coli and Klebsiella spp., the discrimination abilities of hospital-level antibiograms in predicting individual patient AMR were mostly poor, with the areas under the receiver operating curve at 0.686 and 0.715 for ceftriaxone, 0.637 and 0.675 for fluoroquinolones, and 0.576 and 0.624 for trimethoprim-sulfamethoxazole, respectively. The sensitivity and specificity of the antibiogram varied widely by antimicrobial groups and interpretation thresholds with substantial trade-offs. CONCLUSIONS: Conventional hospital antibiograms for E. coli and Klebsiella spp. have limited performance in predicting AMR for individual patients, and their utility in guiding empiric therapy may be low.

Satisfactory In Vitro Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant Pseudomonas aeruginosa But Not against Klebsiella pneumoniae Isolates.

Background: Gram-negative rods are one of the most commonly isolated bacteria within human infections. These microorganisms are typically opportunistic pathogens that pose a serious threat to public health due to the possibility of transmission in the human population. Resistance to carbapenems is one of the most important antimicrobial resistance mechanisms amongst them. The aim of this study was to evaluate ceftolozane-tazobactam in vitro activity against carbapenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae clinical strains. Information on the antimicrobial activity of this antimicrobial against Gram-negative rods was also supplemented with a brief review of the relevant literature. Methods: The research involved 316 strains of Gram-negative rods: P. aeruginosa-206 and K. pneumoniae-110. Results: Of the tested strains, 86.0% P. aeruginosa and 30.0% K. pneumoniae remained susceptible to ceftolozane-tazobactam. Conclusions: Therefore, ceftolozane-tazobactam might be a good option in the treatment of infections caused by carbapenem-resistant P. aeruginosa strains, including those in ICU patients. Meanwhile, due to dissemination of ESBLs among K. pneumoniae strains, infections with this etiology should not be treated with the ceftolozane-tazobactam combination.

Prevotella herbatica sp. nov., a plant polysaccharide-decomposing anaerobic bacterium isolated from a methanogenic reactor.

An obligately anaerobic bacterial strain (WR041T) was isolated from a plant residue sample in a methanogenic reactor. Cells of the strain were Gram-stain-negative, non-motile, non-spore-forming rods. Prevotella paludivivens JCM 13650T was the closest species of the strain based on 16S rRNA gene sequencing (98.9 % similarity). Genome analysis of strain WR041T indicated that the genome size of the strain was 3.52 Mb and the genomic DNA G+C content was 37.5 mol%. Although the 16S rRNA gene sequence similarity of strain WR041T with the closest species was higher than the threshold value of the recommended species delineation (98.7 %), the average nucleotide identity and the digital DNA-DNA hybridization value between them were 91-92 and 45.5 %, respectively, suggesting that strain WR041T represents a novel species in the genus. Strain WR041T essentially required haemin and CO2/Na2CO3 for growth. The strain was saccharolytic and decomposed various polysaccharides (glucomannan, inulin, laminarin, pectin, starch and xylan) and produced acetate and succinate. The optimum growth conditions were 35 °C and pH 6.8. The major cellular fatty acids were branched-chain fatty acids such as anteiso-C15 : 0 and iso-C15 : 0. Menaquinones MK-11 and MK-12 were the major respiratory quinones. Many protein-coding genes which were not found in the genome of P. paludivivens as orthologous genes were detected in the genome of strain WR041T. Based on the differences in the phylogenetic, genomic and physiological characteristics between strain WR041T and related species, the name Prevotella herbatica sp. nov. is proposed to accommodate strain WR041T (=NBRC 115134T = DSM 112534T).

Rapid identification and antimicrobial susceptibility testing of Gram-negative rod on positive blood cultures using MicroScan panels.

Shortening the turnaround time of antimicrobial susceptibility testing (AST) of bacteria permits a significant reduction of patient morbidity, mortality, and cost. Conventional blood culture methods are the gold standard diagnostic test to guide management of patient with sepsis, but the conventional process requires at least 12 to 24 h after the blood culture has been flagged as positive due to requirement for pure colonies. We describe a simple and inexpensive method to obtain faster AST with MicroScan system (Beckman Coulter) directly from positive blood cultures. Conventional and direct identification and AST were performed simultaneously by both methods in 1070 blood cultures, and 9106 MICs were determinated. About 96.5% were correctly identified with the direct method. Overall, categorical agreement was 92.86%. We found 46 very major errors, but globally the results showed a good correlation with the standard method, particularly favorable for E. coli and K. pneumoniae, except amoxicillin-clavulanate and piperacillin-tazobactam. For P. mirabilis, betalactams antibiotics (except second- and third-generation cephalosporines) showed a good correlation, and also a good correlation was found for ciprofloxacine and gentamicine in P. aeruginosa and amoxicillin-clavulanate, ciprofloxacine, gentamicine, and cotrimoxazole in E. cloacae. This method has the main advantage of providing reliable results 1 day earlier, being a simple, fast, and cheap method for identification and antimicrobial susceptibility testing results from positive blood cultures.

Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis.

A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD.

Methylglyoxal: Antimicrobial activity against blood culture isolates of Salmonella Typhi and other Gram negative rods.

OBJECTIVES: To evaluate the activity of Methylglyoxal against the blood culture isolates of Salmonella Typhi and various Gram negative rods and to compare the activity of Methylglyoxal against S. Typhi and other Gram negative rods. METHODS: It was an experimental study conducted at the Department of Microbiology, University of Health Sciences (UHS), Lahore-Pakistan in collaboration with the Department of Microbiology, CMH Lahore, from July 2011 to June 2012. Recent blood culture isolates of S. Typhi and other Gram negative rods were collected from different hospitals of Lahore and kept stored at -80°C. As per the latest CLSI guidelines, morphological, biochemical and serological identification was carried out and antimicrobial susceptibility was tested. A multi-point inoculator was used to carry out agar dilution for determination of MICs of MGO. Results were determined after compilation of data using latest SPSS version. RESULTS: MIC90 of MGO against the clinical isolates of S. Typhi was 0.20 mg/mL (2.8 mM) and against Gram negative rods it was 0.21 mg/mL (3.0 mM). The p-value of MICs of MGO against the isolates of S. Typhi was 0.023 when compared with Gram negative rods (p<0.05; statistically significant). CONCLUSION: MGO has a scientifically proven in vitro antimicrobial activity against blood culture isolates of S. Typhi and various Gram negative rods.

Risk Factors for Colistin Resistance among Gram-Negative Rods and Klebsiella pneumoniae Isolates.

Infections due to colistin-resistant (Colr) Gram-negative rods (GNRs) and colistin-resistant Klebsiella pneumoniae isolates in particular result in high associated mortality and poor treatment options. To determine the risk factors for recovery on culture of Colr GNRs and ColrK. pneumoniae, analyses were chosen to aid decisions at two separate time points: the first when only Gram stain results are available without any bacterial species information (corresponding to the Colr GNR model) and the second when organism identification is performed but prior to reporting of antimicrobial susceptibility testing results (corresponding to the ColrK. pneumoniae model). Cases were retrospectively analyzed at a major academic hospital system from 2011 to 2016. After excluding bacteria that were intrinsically resistant to colistin, a total of 28,512 GNR isolates (4,557 K. pneumoniae isolates) were analyzed, 128 of which were Colr (i.e., MIC > 2 µg/ml), including 68 of which that were ColrK. pneumoniae In multivariate analysis, risk factors for Colr GNRs were neurologic disease, residence in a skilled nursing facility prior to admission, receipt of carbapenems in the last 90 days, prior infection with a carbapenem-resistant organism, and receipt of ventilatory support (c-statistic = 0.81). Risk factors for ColrK. pneumoniae specifically were neurologic disease, residence in a skilled nursing facility prior to admission, receipt of carbapenems in the last 90 days, receipt of an anti-methicillin-resistant Staphylococcus aureus antimicrobial in the last 90 days, and prior infection with a carbapenem-resistant organism (c-statistic = 0.89). A scoring system derived from these models can be applied by providers to guide empirical antimicrobial therapy in patients with infections with suspected Colr GNR and ColrK. pneumoniae isolates.

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group.

BACKGROUND: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). METHODS: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas ß-lactams (noncarbapenems), carbapenems, and multidrug resistance. RESULTS: Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and ß-lactam/ß-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on ß-lactam/ß-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. CONCLUSIONS: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. CLINICAL TRIALS REGISTRATION: NCT02257931.

Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.

PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp. resistant to three or more antibiotic classes and all Stenotrophomonas maltophilia (SM) were defined as multidrug-resistant bacteria (MDR). RESULTS: A total of 80 children (44 males, 0.8-18 years, median 5 years) developed 107 episodes (116 pathogens) of NFGNR bacteremia; Pseudomonas aeruginosa (PA) (51; 43.9%), Acinetobacter baumannii (AB) (21, 18.1%), SM (18, 15.5%); and others (27, 25.2%). The rate of NFGNR bacteremia in children with certain solid tumors (e.g. sarcoma, 12/134 (9.0%)) was comparable to that of hematological malignancies (52/429 (12.2%). Focal infection and septic shock occurred in 16 (14.9%) and four (3.7%) episodes, respectively. Thirty (25.8%) of 116 NFGNR were MDR. The most significant predictors of bacteremia with MDR PA or AB were severe neutropenia (<100 cells/mm3; OR 7.8, p = 0.002), hospital-acquired (OR 16.9, p < 0.0001) and breakthrough (OR 11.2, p < 0.0001) infection. Infection with MDR bacteria was associated with inappropriate empirical therapy. The 30-day mortality was 3/107 (2.8%), all in neutropenic patients with hematological malignancies. CONCLUSIONS: NFGNR bacteremia can present with nonspecific signs or symptoms. MDR NFGNRs are common and compromise treatment options, but mortality is relatively low. Knowledge of local epidemiology, pattern and risk factors for resistance is important to guide empirical therapy.

Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children.

UNLABELLED: To investigate antibiotic resistance among pathogens isolated from urines in a tertiary care children's hospital in Italy. Retrospective analysis of prospectively collected data on antibiotic susceptibility of Gram-negatives isolated from urines at the Istituto Giannina Gaslini, Genoa - Italy from 2007 to 2014. Antibiotic susceptibility was evaluated. By means of CLSI criteria from 2007 to 2010, while from 2011 EUCAST criteria were adopted. Data on susceptibility to amoxicillin-clavulanate, co-trimoxazole, cefuroxime, nitrofurantoin, fosfomycin and ciprofloxacin were evaluated for Escherichia coli, while for other Enterobacteriaceae data were collected for amoxicillin-clavulanate, co-trimoxazole and ciprofloxacin and for ciprofloxacin against Pseudomonas aeruginosa. Univariate and multivariable analyses were performed for risk factors associated with resistance. A total of 4596 Gram-negative strains were observed in 3364 patients. A significant increase in the proportion of resistant strains was observed for E.coli against amoxicillin-clavulanate, cefuroxime and ciprofloxacin and for others Enterobacteriaceae against co-trimoxazole and ciprofloxacin. Resistance to nitrofurantoin and fosfomycin was very infrequent in E.coli. Logistic regression analysis showed that repeated episode of urinary tract infections was a risk factor for E.coli resistance to amoxicillin-clavulanate, co-trimoxazole and cefuroxime, while admission in one of the Units usually managing children with urinary tract malformations was significantly associated to resistance to amoxicillin-clavulanate and cefuroxime. CONCLUSION: In conclusion the present study shows an increase in antibiotic resistance in pediatric bacteria isolated from urines in children, especially in presence of repeated episodes and/or urinary tract malformations. This resistance is worrisome for beta-lactams and cotrimoxazole, and start to increase also for fluoroquinolones while nitrofurantoin and fosfomycin still could represent useful drugs for oral treatment of these infections. WHAT IS KNOWN: • Infections are frequent in patients with urinary tract malformations • Antibiotic prophylaxis can select for resistant pathogens What is New: • The increase in the resistance to ß-lactams, co-trimoxazole or fluoroquinolones in pathogens causing urinary tract infections cause a reduction of drugs with oral formulations available for therapy • Old drugs like nitrofurantoin and fosfomycin can represent attractive compounds for oral treatment of urinary tract infections in children presence of resistance to other drug classes.

Evaluation of phenotypic tests for detection of Amp C beta-lactamases in clinical isolates from a tertiary care hospital of Rawalpindi, Pakistan.

OBJECTIVE: To evaluate sensitivity and specificity of disc approximation test compared to three-dimensional extract test as a phenotypic gold standard test for detection of AmpC beta-lactamase producing Escherichia coli and Klebsiella pneumoniae. METHODS: The cross-sectional validation study was conducted from November 2014 to April 2015 at Army Medical College, Rawalpindi, Pakistan. Extended spectrum beta lactamases (ESBLs) were isolated from various clinical specimens. Screening for AmpC beta-lactamases was done by using cefoxitin disc (30µg) showing inhibition zone diameter of <18mm. Screen-positive isolates were subjected to disc approximation test (DAT) and three-dimensional extract test(3-DET).SPSS 20 was used for statistical analysis. RESULTS: A total of 120 ESBL producing Gram negative rods were included in the study. Out of these 120, 82(68.33%) were found to be AmpC beta-lactamase producing on screening with cefoxitin disc. Amongst these 82 isolates, Escherichia coli were identified in 57(69.51%) and Klebsiella pneumoniae in 25 (30.48%). Phenotypic confirmation by disc approximation test (DAT) identified 43(52.43%). AmpC beta-lactamase producing isolates, whereas gold standard 3-DET showed 38(46.34%) of AmpC beta-lactamase producing isolates. Hence, sensitivity of disc approximation test (DAT) was found to be 88%, specificity was 92%, positive predictive value was 92.68%, negative predictive value was 87.80% and diagnostic accuracy was 90.24%. CONCLUSIONS: Implementation of disc approximation test in the laboratories can help in identifying AmpC beta-lactamase harbouring organisms.

National study reveals gram negative bacteremia on contemporary pediatric AML protocol.

Since bacteremia complicates childhood Acute myeloid leukemia (AML) patients, we assessed bacteremia rates in Israeli children with de-novo AML. All chemotherapy courses of patients enrolled in NOPHO-DBH-2012 AML protocol were included. Down syndrome, acute promyelocytic leukemia were excluded. Among 69 patients, seven had focal bacterial infections. Of the remaining 62, 77.4% had 1-8 bacteremias. Of 238 chemotherapy courses, 98 (41.2%) had bacteremia: 66 (67.3%) predominantly Gram-negative rods (GNR); 28 (28.6%) Gram-positive cocci. Escherichia coli; followed by Klebsiella were most common. Older age, Arab ethnicity, and presenting white blood cell count were associated with an increased risk of bacteremia in the univariable analysis, but these associations were not confirmed in the multivariable analysis. Mortality was high (9.7%), and bacteremia increased PICU utilization 7-fold half from GNR. Most isolates were sensitive to vancomycin/meropenem (94.7%), but GNR had low sensitivity to quinolones (61.8%). High mortality and morbidity of de-novo AML patients from predominantly GNR bacteremia require specific interventions but limited susceptibility to quinolones hampers prophylaxis.

An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Background: Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. Method: This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Results: Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Conclusions: Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

Co-Occurrence of Gram-Negative Rods in Patients with Hematologic Malignancy and Sinopulmonary Mucormycosis.

Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 patients with HM and proven or probable sinopulmonary mucormycosis at MD Anderson Cancer Center (Houston, Texas) from 2000-2020. Seventeen out of sixty-three reviewed patients (27.0%) had sinopulmonary co-occurrence of GNRs (most commonly Pseudomonas aeruginosa and Stenotrophomonas maltophilia) within 30 days of a positive Mucorales culture or histology demonstrating Mucorales species. Eight of seventeen co-isolations of Mucorales and GNRs were found in same-day samples. All 15 patients with GNR co-occurrence and reported antimicrobial data had received anti-Pseudomonal agents within 14 days prior to diagnosis of mucormycosis and 5/15 (33.3%) had received anti-Stenotrophomonal agents. Demographic and clinical characteristics of patients with and without GNR co-occurrence were comparable. Forty-two-day all-cause mortality was high (34.9%) and comparable in patients with (41.2%) and without (32.6%) GNR detection (p = 0.53). In summary, over a quarter of heavily immunosuppressed patients with sinopulmonary mucormycosis harbored GNRs in their respiratory tract. Although no impact on survival outcomes was seen in a background of high mortality in our relatively underpowered study, pathogenesis studies are needed to understand the mutualistic interplay of GNR and Mucorales and their influence on host responses.

Addressing the Global Threat of Multidrug-Resistant Infections: The Role of Ceftazidime-Avibactam Revisited.

Background and objective Bloodstream infections (BSIs) due to multidrug-resistant Gram-negative bacteria (MDR-GNB) pose a significant global health threat amid rising antimicrobial resistance (AMR). This study aimed to investigate the efficacy of ceftazidime-avibactam (CZA) as a therapeutic option for these infections, addressing the urgent need for novel treatments. Materials and methods This study was conducted over one year in the Department of Microbiology, JSS Medical College and Hospital, Mysuru, India, and employed a laboratory-based prospective design. From a total of 376 positive blood cultures, 147 multidrug-resistant (MDR) organisms were identified, and 100 were randomly selected for final analysis. Susceptibility testing via disk diffusion and minimum inhibitory concentration (MIC) determination was performed to evaluate CZA efficacy. Results Klebsiella pneumoniae (K. pneumoniae) was the predominant (78%) organism among the subsets, with varying susceptibility patterns observed across species. The overall CZA susceptibility was 45%, with significant discrepancies between disk diffusion and gold standard testing. Notably, there was limited efficacy against Pseudomonas aeruginosa (P. aeruginosa) Conclusions This study underscores the pressing need for reliable testing methods and novel treatment strategies in combating MDR infections. Further research with larger sample sizes is imperative to validate our findings and guide clinicians effectively in addressing this critical health challenge.

In Vitro Activity of Eravacycline against Carbapenemase-Producing Gram-Negative Bacilli Clinical Isolates in Central Poland.

Eravacycline is a novel antibiotic of the tetracycline class with activity against a broad spectrum of clinically significant bacteria, including multi-drug-resistant organisms. For this reason, it may be an alternative to treating critical infections of this etiology. We aimed to assess the in vitro effectiveness of eravacycline to carbapenemase-producing Gram-negative bacilli clinical isolates identified in hospitals in Lódz, Poland. We analyzed 102 strains producing KPC, MBL, OXA-48, GES, and other carbapenemases. Eravacycline susceptibility was determined following the EUCAST guidelines. The highest susceptibility was found in KPC (73%) and MBL (59%) strains. Our results confirmed in vitro the efficacy of this drug against carbapenem-resistant strains. However, eravacycline has been indicated only for treating complicated intra-abdominal infections, significantly limiting its use. This aspect should be further explored to expand the indications for using eravacycline supported by evidence-based medicine. Eravacycline is one of the drugs that could play a role in reducing the spread of multidrug-resistant microorganisms.

Antimicrobial susceptibility and clinical characteristics of multidrug-resistant polymicrobial infections in Pakistan, a retrospective study 2019-2021.

Background: We determined the prevalence of antimicrobial resistance (AMR) in polymicrobial pathogens in Pakistan. Methods: A total of 70,518 clinical samples were collected aseptically and confirmation of isolates and antibiogram were performed by the VITEK 2 system. Results: Of 70,518 samples, 441 (0.62%) were polymicrobial samples, with 882 (1.2%) polymicrobial pathogens with 689 (78.1%) Gram-negative rods (GNRs), 166 (18.8%) Gram-positive cocci and 27 (3.1%) Candida albicans. Among GNRs, 28.8% were Escherichia coli and 25.9% were Klebsiella pneumoniae. Majority, 15.1% of Pseudomonas aeruginosa and K. pneumoniae were found in combination. 30.1% of isolates were ESBL producers, 9.7% carbapenem-resistant organisms, 35.5% MRSA and 6.0% VRE. 100% of E. coli were resistant to ampicillin and 98% of K. pneumoniae were resistant to piperacillin. Conclusion: A high prevalence of AMR in polymicrobial pathogens was observed.

Infections caused by one or more types of bacteria, viruses, fungi or parasites ­ known as polymicrobial infections ­ are a threat to health. These infections cause serious illness and are linked to high numbers of deaths, long hospital stays and high costs of treatment. Usually, polymicrobial infections are treated with combinations of antimicrobials. However, microbes becoming less susceptible to antimicrobials (known as antimicrobial resistance) is an increasing problem. To find out how common resistance is in Pakistan, this study tested 70,518 clinical samples. Of these, 441 tested positive for polymicrobial infections. These included Candida albicans, Gram-positive cocci and Gram-negative rods infections. Many of these were resistant to widely used antibiotics such as penicillins, cephalosporins, quinolones and fluoroquinolones. This study concluded that hospitals in Pakistan have a high prevalence of resistance and that better cleanliness practices should be put in place to combat this.

Carbapenem-Resistant Gram-Negative Fermenting and Non-Fermenting Rods Isolated from Hospital Patients in Poland-What Are They Susceptible to?

Gram-negative fermenting and non-fermenting bacteria are important etiological factors of nosocomial and community infections, especially those that produce carbapenemases. Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most frequently-detected carbapenemase-producing microorganisms. The predominant type of resistance is metallo-ß-lactamase (MBL). These bacteria are predominantly isolated from bronchial alveolar lavage, urine, and blood. Carbapenemase-producing Enterobacterales (CPE) strains are always multi-drug-resistant. This significantly limits the treatment options for this type of infection, extends the time of patient hospitalization, and increases the risk of a more severe and complicated disease course. Preventing the transmission of these microorganisms should be a major public health initiative. New antibiotics and treatment regimens offer hope against these infections.

Emergence of colistin-resistant gram-negative rods in intensive care units: A cross-sectional study from a developing country.

Objectives: To determine the clinical features, outcomes, and factors associated with the emergence of colistin-resistant gram-negative rods isolated from patients admitted to intensive care units. Methods: This cross-sectional study was conducted at the intensive care units of Liaquat National Hospital, from April 2019 to February 2020. Gram-negative rods resistant to colistin with minimum inhibitory concentrations ⩾ 4 mcg/mL according to Clinical and Laboratory Standards Institute criteria as reported in cultures were included. Clinical, demographical data and treatment given were recorded and analyzed using SPSS version 25. Results: A total of 93 patients were included; 58.1% were males. The mean age of patients was 59.48 ± 18.36 years. The most common organism isolated was Klebsiella pneumoniae (91.4%). The most common specimen was the tracheal (62.4%). Ventilator-acquired pneumonia was seen in 38.7%. The most common co-morbid disease seen in patients was diabetes (41%); 77% had a symptomatic infection and were treated with a combination of 2 or more antibiotics, most commonly meropenem plus fosfomycin. The most common susceptible antibiotics were fosfomycin (72%) and tigecycline (50.5%). Mean intensive care unit stay and total duration of hospital stay were prolonged (16.83 ± 12.93 and 23.34 ± 17.52 days, respectively). Forty-eight (62.3%) patients with symptomatic infection with colistin-resistant isolates were treated and discharged, and mortality was seen in 23 (29.9%). A significant association was found between mortality and symptomatic infection, endotracheal intubation with mechanical ventilation (p = 0.003), and a prolonged hospital stay of >20 days (p = 0.041). Conclusion: Colistin-resistant gram-negative rods pose a significant problem especially in developing countries because of limited therapeutic options. Stringent infection control and comprehensive antimicrobial stewardship programs are needed to overcome this challenge.

Bacteremia in Children with Solid Tumors: Etiology, Antimicrobial Susceptibility, Factors Associated with Multidrug Resistance, and Mortality.

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.