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Background: Antimicrobial resistance research in uncomplicated urinary tract infection typically focuses on the main causative pathogen, Escherichia coli; however, little is known about the antimicrobial resistance burden of Klebsiella species, which can also cause uncomplicated urinary tract infections. This retrospective cohort study assessed the prevalence and geographic distribution of antimicrobial resistance among Klebsiella species and antimicrobial resistance trends for K. pneumoniae in the United States (2011–2019). Methods: K. pneumoniae and K. oxytoca urine isolates (30-day, non-duplicate) among female outpatients (aged ≥ 12 years) with presumed uUTI at 304 centers in the United States were classified by resistance phenotype(s): not susceptible to nitrofurantoin, trimethoprim/sulfamethoxazole, or fluoroquinolone, extended-spectrum β-lactamase-positive/not susceptible; and multidrug-resistant based on ≥ 2 and ≥ 3 resistance phenotypes. Antimicrobial resistance prevalence by census division and age, as well as antimicrobial resistance trends over time for Klebsiella species, were assessed using generalized estimating equations. Results: 270,552 Klebsiella species isolates were evaluated (250,719 K. pneumoniae; 19,833 K. oxytoca). The most frequent resistance phenotypes in 2019 were nitrofurantoin not susceptible (Klebsiella species: 54.0%; K. pneumoniae: 57.3%; K. oxytoca: 15.1%) and trimethoprim/sulfamethoxazole not susceptible (Klebsiella species: 10.4%; K. pneumoniae: 10.6%; K. oxytoca: 8.6%). Extended-spectrum β-lactamase-positive/not susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively. K. pneumoniae resistance phenotype prevalence varied (p < 0.0001) geographically and by age, and increased over time (except for the nitrofurantoin not susceptible phenotype, which was stable and > 50% throughout). Conclusions: There is a high antimicrobial resistance prevalence and increasing antimicrobial resistance trends among K. pneumoniae isolates from female outpatients in the United States with presumed uncomplicated urinary tract infection. Awareness of K. pneumoniae antimicrobial resistance helps to optimize empiric uncomplicated urinary tract infection treatment. [ABSTRACT FROM AUTHOR]

Background There are limited treatment options for uncomplicated urinary tract infection (uUTI) caused by resistant pathogens. Sulopenem etzadroxil/probenecid (sulopenem) is an oral thiopenem antibiotic active against multidrug-resistant pathogens that cause uUTIs. Methods Patients with uUTI were randomized to 5 days of sulopenem or 3 days of ciprofloxacin. The primary endpoint was overall success, defined as both clinical and microbiologic response at day 12. In patients with ciprofloxacin-nonsusceptible baseline pathogens, sulopenem was compared for superiority over ciprofloxacin; in patients with ciprofloxacin-susceptible pathogens, the agents were compared for noninferiority. Using prespecified hierarchical statistical testing, the primary endpoint was tested in the combined population if either superiority or noninferiority was declared in the nonsusceptible or susceptible population, respectively. Results In the nonsusceptible population, sulopenem was superior to ciprofloxacin, 62.6% vs 36.0% (difference, 26.6%; 95% confidence interval [CI], 15.1 to 7.4; P <.001). In the susceptible population, sulopenem was not noninferior to ciprofloxacin, 66.8% vs 78.6% (difference, −11.8%; 95% CI, −18.0 to 5.6). The difference was driven by a higher rate of asymptomatic bacteriuria (ASB) post-treatment in patients on sulopenem. In the combined analysis, sulopenem was noninferior to ciprofloxacin, 65.6% vs 67.9% (difference, −2.3%; 95% CI, −7.9 to 3.3). Diarrhea occurred more frequently with sulopenem (12.4% vs 2.5%). Conclusions Sulopenem was noninferior to ciprofloxacin in the treatment of uUTIs. Sulopenem was superior to ciprofloxacin in patients with uUTIs due to ciprofloxacin-nonsusceptible pathogens. Sulopenem was not noninferior in patients with ciprofloxacin-susceptible pathogens, driven largely by a lower rate of ASB in those who received ciprofloxacin. Clinical Trial Registration NCT03354598. [ABSTRACT FROM AUTHOR]

Objective: To evaluate optimal regimens for perioperative antimicrobial prophylaxis in transurethral procedures by examining antimicrobial susceptibility patterns in the United States.Materials and Methods: Through several methods, we attempted to attain an antibiogram for each state. We focused on microbes known to cause infections after transurethral surgeries and antibiotics referred to in current or prior recommendations and compared susceptibility rates across states using Kruskal Walis tests and the Dwass, Steel, Critchlow-Fligner tests. We also examined susceptibility to (non-ceftazidime) third generation cephalosporins.Results: Data is included from 40 states. For each microbe studied, there was significant variability in sensitivity to antibiotics studied. Current first line recommendations for antimicrobial prophylaxis include first generation cephalosporins with 82%, 80%, and 87% mean coverage for E coli, Proteus, and Klebsiella respectively and trimethoprim-sulfamethoxazole with 74%, 80%, and 93% coverage, respectively. Susceptibility to aminoglycosides is 91%, 92%, and 96%, respectively and to third generation cephalosporin, it is 92%, 99%, and 94%.Conclusion: Current first line recommended antimicrobials for prophylaxis in transurethral procedures provide overall poor predicted coverage based on our database of antibiograms. Alternatives exist that have higher predicted susceptibility, though clinical significance of this and risk of resultant antimicrobial resistance is unknown. Urologists should consider local patterns when selecting antimicrobial prophylaxis for their patients. [ABSTRACT FROM AUTHOR]

Objective: Infections caused by bacteria growing in blood cultures are important medical problems that cause high morbidity and mortality. The aim of this study is to examine the changes in antibiotic susceptibility and the bacteria isolated from blood samples from various clinics in the five-year period and to determine the antimicrobials that can be chosen in empirical treatment in blood stream infection in our hospital. Methods: Blood samples from our laboratories were evaluated retrospectively between during 2013- 2017. Samples were incubated in an automated system of BACTEC-FX(BD,USA). Conventional methods and automated systems (Phoenix,BD,USA) have been used to identify bacteria. Antibiotic susceptibilities of isolated bacteria were evaluated using the automated systems (Phoenix,BD,USA). Results: A total of 4597 bacterial reproductions that isolated from the blood samples including 1972 (42.9%) gram positive and 2625 (57.1%) gram negative were included in the study. The most frequently isolated gram positive bacteria were Staphylococcus aureus (15.3%) and the gram negative bacteria were Escherichia coli (18,6%). Staphylococcus aureus and coagulase negative staphylococci (CNS) isolates no resistance to glycopeptide or linezolid was found. Resistance of vancomycin and teicoplanin in enterococci was determined as 9.7% while linezolid resistance was 2%. Extended spectrum beta lactamase production was detected in E. coli isolates 46.7%, Klebsiella pneumoniae isolates 63.4%, an increase has been observed in E. coli isolates over the last three years. Over the years it has been determined that resistance of trimethoprim-sulfamethoxazole in S. aureus and CNS isolates were decreases. However, it has been determined that increased resistance rates of netilmisin in E. coli and K. pneumoniae isolates, aztreonam, imipenem and meropenem resistance in Pseudomonas aeruginosa isolates. The most effective antimicrobials were linezolid and glycopeptides in staphylococci and enterococci, carbapenems and amikacin in E. coli, and colistin in K. pneumoniae, Acinetobacter baumannii and P. aeruginosa isolates in our study. Conclusion: The diversity of bacteria isolated from blood cultures and susceptibility to antibiotics varies according to geographical regions, hospital flora and antibiotics used in the hospital. For this reason, it was think that each hospital should determine its own bacterial distribution and antibiotic susceptibility at certain intervals and rational drug use policies have to be designated according to these results to provide benefits in fighting with resistant microorganisms. [ABSTRACT FROM AUTHOR]

Eggs in the United States are typically washed using chemical sanitizers such as quaternary ammonia (QA) or chlorine. Such treatments generate wash water, which could be potentially hazardous to the environment. A novel, nonthermal sanitization technique for washing shell eggs using cold plasma-activated water (PAW) was investigated in this study. The inactivation efficacy of PAW on Klebsiella michiganensis and the impact of PAW on the cuticle of the eggshell and shell strength were tested in comparison to QA. Washing inoculated eggs with PAW and QA achieved a similar microbial reduction (>5.28 log CFU/egg). Colorimetric analysis showed that ∆ E -value for PAW-treated eggs was significantly lower than QA-treated eggs, suggesting higher cuticle coverage in eggs treated with PAW. The texture analysis to test for shell egg strength indicated that washing eggs with PAW did not affect the structural integrity of the eggshell when compared to eggs washed with QA. According to this study, PAW has the potential as an alternative to commercial sanitizers like QA in the egg-washing industry. PAW does not detrimentally impact shell strength or cuticle coverage and provides similar microbial reduction efficacy. [ABSTRACT FROM AUTHOR]

Prevalence of carbapenem-resistant gram-negative infections in the United States predominated by Acinetobacter baumannii and Pseudomonas aeruginosa. To the editor, I Pseudomonas aeruginosa i is one of the most common causes of health care infection in the United States. Carbapenem-resistant Pseudomonas aeruginosa at US emerging infections program sites, 2015. [Extracted from the article]

• Gram-negative isolates from children in 79 US and European hospitals were tested. • For all Enterobacteriaceae, 94.6% were susceptible to ceftolozane-tazobactam. • For Pseudomonas aeruginosa , 97.4% were susceptible to ceftolozane-tazobactam. Ceftolozane-tazobactam is a combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. Ceftolozane-tazobactam was approved by the US Food and Drug Administration in 2014 and by the European Medicines Agency in 2015 for use in adults to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections with metronidazole. Studies for paediatric indications are planned. The Programme to Assess Ceftolozane-Tazobactam Susceptibility monitors the resistance of ceftolozane-tazobactam to Gram-negative isolates worldwide. In total, 6240 Gram-negative isolates were collected between 2012 and 2016 from paediatric patients (<18 years old) in 31 US hospitals (4207 isolates) and 48 European hospitals (2033 isolates), and tested for susceptibility (S) to ceftolozane-tazobactam by broth microdilution. Other antibiotics tested included amikacin, colistin and meropenem. The most common infection type in hospitalized paediatric patients was pneumonia (n =2018), followed by urinary tract infection (n =1569) and bloodstream infection (n =1236). In total, 4316 Enterobacteriaceae and 1765 non-enterics were isolated. The most common species were Escherichia coli (n =1919), Pseudomonas aeruginosa (n =1236) and Klebsiella pneumoniae (n= 709). In all regions, the three most active antimicrobials against paediatric Enterobacteriaceae isolates were amikacin (99.0%S), meropenem (98.9%S) and ceftolozane-tazobactam (94.6%S). For all P. aeruginosa , colistin (98.9%S) and ceftolozane-tazobactam (97.4%S) were the most active. In conclusion, for all Enterobacteriaceae, ceftolozane-tazobactam was the most potent cephalosporin tested, with only meropenem and colistin having higher susceptibility rates. For P. aeruginosa , ceftolozane-tazobactam was the most potent β-lactam and had a similar susceptibility rate to colistin. [ABSTRACT FROM AUTHOR]

Background: Infections caused by extended-spectrum beta-lactamases (ESBL) producing Gram-negative bacteria has emerge as a global threat in clinical practices. The treat is more serious in developing countries due to inappropriate use, poor adherence, use of counterfeit, sub-standard antibiotics and poor infection control practices. Data on ESBL producing Gram-negative bacteria are limited in developing countries including Ethiopia. The aim of this study was therefore, to describe the burden of ESBL producing Gram negative pathogens isolated from patients attending at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Amhara region. Materials and methods: A total of 532 clinical samples of blood, urine, stool, wound, abscess, ear discharge, nasal discharge, cervical discharge and body fluid specimens were aseptically collected and bacteriologically processed. Identification of the bacterial species was performed using an automated system (Vitek-2 Compact 27530, USA) and antibiotic susceptibility test was determined by disk diffusion method and selection of antibiotics were in accordance with CLSI guidelines. The MDR pattern of the Gram-negative pathogens was assessed using phenotypic methods of ESBL and carbapenemase production following standard procedure. Result: A total of 532 samples were processed and 263 pathogens were isolated. Of these, 185 (70.3%) were Gram-negative and 78 (29.7%) Gram-positive. Of the Gram-negative bacteria the high proportion of the isolates were identified from blood 146/185 (78.9%) and 29/185 (15.7%) were from urine cultures. The most common isolate in all clinical samples was Klebsiella pneumoniae 97/185 (52.4%) followed by Escherichia coli 23/185 (12.4%), Acinetobacter baumannii 15/185 (17.6%) and Enterobacter aerogenes 12/185(6.5%). Of the total Gram negatives, the prevalence of MDR was 148/185 (80.0%). Of the MDR isolates the prevalence of ESBL producers were, 127/148 (85.8%) and 24/148 (16.2%) were carbapenemase producers. Conclusion and recommendation: Prevalence of MDR and ESBL producing Gram-negative pathogens in this hospital is alarmingly high. Therefore, continuous monitoring of the problem with effective infection prevention and careful selection of empirical therapy are warranted in the study area. [ABSTRACT FROM AUTHOR]

Background: Treatment of infections in the ICU represents a great challenge, especially infections caused by Gram-negative organisms. Rapid introduction of appropriate antimicrobial therapy is crucial to reduce mortality, and resistance rates in the ICU can be elevated due to antimicrobial selection pressure.Objectives: To evaluate the frequency and antimicrobial susceptibility of Gram-negative bacteria isolated from patients with pneumonia hospitalized in ICUs.Methods: A total of 6091 bacterial isolates were consecutively collected from 75 US medical centres in 2015-17 as part of the International Network for Optimal Resistance Monitoring (INFORM) programme and tested for susceptibility to multiple antimicrobial agents at a central laboratory by reference broth microdilution methods.Results: The most common organisms were Staphylococcus aureus (30.0%), Pseudomonas aeruginosa (20.7%), Klebsiella spp. (11.8%), Enterobacter spp. (8.3%), Escherichia coli (7.1%) and Stenotrophomonas maltophilia (5.1%). Colistin (99.8% susceptible), ceftazidime/avibactam (96.8% susceptible in 2015-17 and 96.2% in 2017) and ceftolozane/tazobactam (96.5% susceptible in 2017) were the most active compounds against P. aeruginosa. Ceftazidime/avibactam (100.0% susceptible), amikacin (99.4% susceptible) and meropenem (97.6% susceptible) were the most active compounds against Enterobacteriaceae. S. maltophilia and Acinetobacter baumannii exhibited high resistance rates to most antimicrobials tested.Conclusions: Gram-negative bacteria were isolated from 67.1% of the patients and P. aeruginosa and Enterobacteriaceae represented >80% of these organisms. Ceftazidime/avibactam and amikacin provided the best coverage against Gram-negative organisms overall. [ABSTRACT FROM AUTHOR]

Background The epidemiology of antibiotic-resistant Enterobacteriaceae intestinal carriage in healthy US children has not been well characterized. Methods Children between 14 days and 14 years of age were enrolled during well-child visits in Oakland, California, Kansas City, Kansas, and Nashville, Tennessee, between December 2013 and March 2015. Data on recent antibiotic use by the child and travel and hospitalization history of all members of each child’s household were obtained with a risk-factor survey. Stool specimens collected from the subjects were screened for extended-spectrum β-lactamase-producing (ESBL-P) bacteria using CHROMagar ESBL medium. Putative ESBL-P Escherichia coli and Klebsiella colonies underwent phenotypic confirmation by double-disk synergy testing; confirmed third-generation cephalosporin-resistant (3GCR) isolates underwent additional antibiotic-susceptibility testing. Results In 519 subjects, the overall 3GCR Enterobacteriaceae carriage rate was 4.4% (n = 23) and ranged from 3.4% to 5.1% among the study sites. The ESBL-P Enterobacteriaceae carriage rate was 3.5% (n = 18). The rates of 3GCR Enterobacteriaceae carriage was highest in 1 to <2 year olds at 6.5%, and was 5.2% in <5 year-olds vs 1.7% in ≥5-year-olds (P =.11). 3GCR and ESBL-P Enterobacteriaceae carriage was associated with international travel within the previous year; 11.1% of ESBL-P Enterobacteriaceae carriers reported this history compared with 1.6% of noncarriers (P =.004). No other queried factor was found to increase risk. Of the 24 analyzed 3GCR isolates, 58% were multidrug resistant. Conclusions The 3GCR Enterobacteriaceae carriage rate exceeds 5% in healthy US children <5 years of age. International travel within the previous year increased the risk of 3GCR and ESBL-P Enterobacteriaceae carriage. In contrast, we found no differences in the rates of hospitalization or recent antibiotic exposure between carriers and noncarriers. Young children, who have the highest prevalence of colonization, might be a sentinel population to study to gain a better understanding of community sources of antibiotic-resistant Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

Contemporary (2012) β-lactamase-producing isolates ( n=493) from U.S. hospitals were tested against ceftaroline-avibactam. Klebsiella spp., Escherichia coli and Proteus mirabilis isolates displaying the Clinical and Laboratory Standards Institute (CLSI) screening criteria for extended spectrum β-lactamase (ESBL) production were evaluated. Isolates carried genes encoding CTX-M ( n=316, CTX-M-14-like and -15-like), KPC ( n=45), CMY-2-like ( n=54), or SHV enzyme with ESBL activity ( n=78). Ceftaroline-avibactam inhibited 98.2% of the isolates at ≤0.5 μg/mL, and all strains were inhibited by ≤2 μg/mL of this novel β-lactamase-inhibitor combination. These results confirm that ceftaroline-avibactam could be a useful therapeutic option for Enterobacteriaceae isolates producing β-lactamases that are prevalent in the United States. [ABSTRACT FROM AUTHOR]

This study represents a review of the incidence of extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella species causing infections over a 7-year period and provides a comparison of patient demographics, comorbidities, and ESBL subtypes between community-associated (CA) versus health care-associated (HA) infections. All ESBL-producing bacterial isolates between 2003 and May 2011 at Madigan Army Medical Center were evaluated and reviewed. Polymerase chain reaction (PCR) for ESBL subtypes TEM, SHV, and CTX-M was performed. Demographics and comorbidities associated with infection, ESBL subtype, and antibiotic susceptibility were compared for HA and CA infection. A total of 122 isolates were included in the analysis. From 2005 to 2010, incidence of ESBLs in E. coli increased from 0.13% to 1.0%, and incidence in Klebsiella species rose from 1.0% to 2.55%. CA infections were more likely in females (p < 0.01), age <60 (p < 0.01), urinary source (p < 0.01), and recurrent urinary tract infections (p = 0.02). 42% of CA infections had no associated comorbidity. CTX-M was the predominant subtype in CA infections. Coresistance was high in both HA and CA infection. These data emphasize the need for ongoing monitoring of local microbial epidemiologic trends as changes in prescribing practices may become necessary if resistance continues to spread. [ABSTRACT FROM AUTHOR]

We studied antimicrobial-resistant Klebsiella pneumoniae for 1998-2010 by using data from The Surveillance Network. Susceptibility results (n = 3,132,354) demonstrated significant increases in resistance to all antimicrobial drugs studied, except tetracycline. Cross-resistance among carbapenem-resistant K. pneumoniae was lower for tetracycline and amikacin. [ABSTRACT FROM AUTHOR]

Study Objective. To determine the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures against common nosocomial pathogens. Design. Pharmacodynamic Monte Carlo simulation model. Data Source. Microbiologic data generated from isolates from the 14 centers in the United States in the 2004 Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance study. Patients. Five thousand simulated patients with infection. Measurements and Main Results. Pharmacokinetic profiles of the patients were simulated to determine the bactericidal cumulative fraction of response (CFR) for commonly used intravenous regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam against Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella species. Ciprofloxacin and levofloxacin had CFRs among the lowest of all drugs against all pathogens, especially P. aeruginosa (40.4-65.5%) and A. baumannii (43.6-48.2%). The low CFR of about 78% against E. coli with these two agents was of particular concern. Among the β-lactams, only high-dose cefepime and ceftazidime regimens achieved CFRs of greater than 90% against P. aeruginosa, followed by cefepime 2 g every 12 hours and the carbapenems (86.3-89.7%). No regimen achieved an optimum CFR for A. baumannii. All β-lactam regimens achieved a greater-than-90% likelihood of having bactericidal CFRs against Enterobacteriaceae. Conclusion. Because of the continual evolution of resistance among gram-negative bacteria in the United States, reevaluation of optimum dosing strategies for β-lactam and fluoroquinolone antibiotics is necessary. [ABSTRACT FROM AUTHOR]

We examined Escherichia coli and Klebsiella spp. from US hospitals for class 1 integrons. Of 320 isolates, 181 (57%) were positive; association of integrons with resistance varied by drug and organism. Thus, determining integron epidemiology will improve understanding of how antibacterial resistance determinants spread in the United States. [ABSTRACT FROM AUTHOR]

Background We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals. Methods A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype). Results The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA. Conclusion CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Nineteen isolates of carbapenem-resistant Klebsiella species were recovered from 7 hospitals in New York City. Most K. pneumoniae belonged to a single ribotype. Nucleotide sequencing identified KPC-2, a carbapenem- hydrolyzing β-lactamase. In 3 strains, TEM-30, an inhibitor-resistant β-lactamase, was detected. Carbapenem- resistant Klebsiella species possessing KPC-2 are endemic in New York City. This study documents the identification of an inhibitor-resistant TEM β-lactamase in the United States. [ABSTRACT FROM AUTHOR]

The article focuses on the Carbapenem resistance due to metalloß-lactamases is quite uncommon in the U.S. It mentions that antimicrobial susceptibility testing for the aztreonam-avibactam combination is available through the Antimicrobial Resistance Network's Expanded Antimicrobial Susceptibility Testing for Hard-to-Treat Infections Program. It also mentions that tigecycline and eravacycline had the greatest in vitro activity among all U.S. Food and Drug Administration (FDA).

The authors explore the prevalence of carbapenem resistance and carbapenemase production in isolates of Escherichia (E) coli and Klebsiella species (spp) from Europe and the Americas. Resistance to imipenem and/or meropenem was observed in 2.0% of E. coli and Klebsiella spp. isolates. Carbapenemase production and carbapenem resistance were higher in Klebsiella spp. isolates. About 1.4% of the isolates showed carbapenemase production using Hodge test (MHT) and polymerase chain reaction (PCR).

The frequency and antimicrobial susceptibility of organisms causing bloodstream infections in the United States were evaluated by consecutively collecting (1/patient) 9210 bacterial isolates from 33 US medical centers in 2015–2017. Isolates were susceptibility tested by reference broth microdilution methods. Whole genome sequencing was performed on carbapenem-resistant Enterobacteriaceae (CRE). The most common organisms were Staphylococcus aureus (24.3%), Escherichia coli (20.8%), and Klebsiella pneumoniae (9.1%). Overall, 50.0% of isolates were gram-negative bacilli and 41.4% were Enterobacteriaceae. The most active agents against Enterobacteriaceae were ceftazidime–avibactam (99.9% susceptible), amikacin (99.7% susceptible), and the carbapenems meropenem and doripenem (99.1% susceptible). Among 28 CRE isolates (0.7% of Enterobacteriaceae), 21 produced a KPC-like carbapenemase, 2 an NMD-like, and 1 a KPC-17 and an NDM-1. Colistin (100.0% susceptible), ceftolozane–tazobactam (98.7% susceptible), ceftazidime–avibactam (98.2% susceptible), amikacin (97.9% susceptible), and tobramycin (95.6% susceptible) were very active against Pseudomonas aeruginosa. Among S. aureus isolates, 57.8% were oxacillin-susceptible. [ABSTRACT FROM AUTHOR]

Background Infections with metallo-β-lactamase (MBL)-producing organisms are emerging in the United States. Treatment options for these infections are limited. We describe MBL genes among carbapenemase positive carbapenem-resistant Enterobacteriaceae (CP-CRE) and Pseudomonas aeruginosa (CP-CRPA) isolates tested during the first two years of the Antibiotic Resistance Laboratory Network (AR Lab Network). Methods State and local public health laboratories tested CRE and CRPA isolates for organism identification, antimicrobial susceptibility, and PCR-based detection of bla KPC, bla NDM, bla OXA-48-like, bla VIM, and bla IMP carbapenemase genes. All testing results were sent to CDC at least monthly. Results Since January 2017, the AR Lab Network tested 21,733 CRE and 14,141 CRPA. CP-CRE were detected in 37% of CRE; 2% of CRPA were CP-CRPA. Among CP-CRE, 9% (686/8016) were MBL-producers (NDM, VIM, or IMP). Among MBL-producers, a bla NDM gene was detected most often (81%; 551/686). bla NDM were most common among Klebsiella spp. (47%; 261/551), bla IMP were most common among Providencia spp. (53%; 40/75), bla VIM was most common among Enterobacter spp. (19%; 25/62). Twelve percent (96) of MBL CP-CRE contained more than one carbapenemase gene. Among CP-CRPA, 73% (218/300) were MBL producers and bla VIM was the most common gene (62%; 186). Three (1%) MBL CP-CRPA contained more than one carbapenemase. Conclusion Increased testing of CRE and CRPA isolates through the AR Lab Network has facilitated early and rapid detection of hard-to-treat infections caused by MBL-producing organisms across the United States. The widespread distribution of MBL genes highlights the continued need for containment strategies that help prevent transmission between patients and among healthcare facilities. To support therapeutic decisions for severe infections caused by MBL-producing organisms, the AR Lab Network is now offering rapid susceptibility testing against aztreonam/avibactam, using digital dispenser technology. This testing program aims to close the gap between the availability of new drugs or drug combinations and the availability of commercial AST methods, thereby improving patient safety and antimicrobial stewardship. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum β-lactamase (ESBL)–producing organisms almost uniformly display nonsusceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone-nonsusceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. Methods All consecutive Escherichia coli , Klebsiella pneumoniae , Klebsiella oxytoca , or Proteus mirabilis clinical isolates with ceftriaxone minimum inhibitory concentrations (MICs) of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for β-lactamase genes using a DNA microarray–based assay. Results Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (bla CTX-M, bla SHV, bla TEM) and/or plasmid-mediated ampC (p- ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p- ampC genes in 2 (0.5%), and both ESBL and p- ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or ≥4 ESBL or p- ampC genes. The most common ESBL genes were of the bla CTX-M-1 group (includes bla CTX-M-15), and the most common p- ampC gene was bla CMY-2. Conclusions There is considerable diversity in the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making. [ABSTRACT FROM AUTHOR]

Objectives To assess the spectrum and potency of ceftaroline, a novel anti-methicillin-resistant staphylococcal cephalosporin, against a 2008 surveillance collection of clinical isolates from patients in the USA and Europe. Methods A collection of 14 169 isolates of various bacterial species from complicated skin and skin structure infections (cSSSIs) was tested for susceptibility to ceftaroline and 19 comparator agents in a central reference laboratory using CLSI broth microdilution methods. Organisms were received from 55 medical centres; 27 in the USA and 28 in Europe (12 countries, including Israel). The clonality of isolates of Staphylococcus aureus with elevated ceftaroline MICs (4 mg/L) was determined by PFGE and single and multilocus sequence typing, and the mechanism of ceftaroline non-susceptibility was assessed by molecular methods (PCR amplification and sequencing). Results Ceftaroline, the active component of the parenteral prodrug ceftaroline fosamil, was active against 2988 methicillin-resistant S. aureus (MRSA) isolates, with an MIC90 of 1 mg/L. The MIC90 for methicillin-susceptible strains was 0.25–0.5 mg/L. Ceftaroline was additionally active against coagulase-negative staphylococci (MIC90, 0.5–1 mg/L), Enterococcus faecalis (MIC50, 2 mg/L), β-haemolytic and viridans group streptococci (MIC90, 0.015–0.25 mg/L) and three commonly isolated Enterobacteriaceae (Escherichia coli, Klebsiella spp. and Proteus mirabilis; MIC90 values of 0.25 to >16 mg/L). All but four isolates of MRSA (0.13%) had ceftaroline MIC values of ≤2 mg/L. The isolates for which ceftaroline MICs were 4 mg/L were clonal (single Greek hospital) and had detectable mecA mutations (N146K, N204K, E150K and H351N). Conclusions The ceftaroline yearly (2008) surveillance for the USA and Europe documented low MIC50/90 values for MRSA isolates at 1/1 and 1/2 mg/L, respectively. Ceftaroline demonstrated promising potency and coverage against Gram-positive and -negative pathogens known to cause cSSSIs, including MRSA and β-haemolytic streptococci. [ABSTRACT FROM PUBLISHER]

States that cutting back on cephalosporin use causes a very rapid fall in bacterial resistance to the antibiotics. A study at the New York Hospital Medical Centre of Queens in Flushing, New York on ceftazidime-resistant klebsiella infections in the intensive-care unit; The increase in resistance of Pseudomonas aeruginosa to imipenem; Comments of Gary French, professor of microbiology at St. Thomas's Hospital in London, England. INSET: Variant penicillin described.