Newer ␤-lactamases such as extended-spectrum ␤-lactamases (ESBLs), transferable AmpC ␤-lactamases, and carbapenemases are associated with laboratory testing problems of false susceptibility that can lead to inappropriate therapy for infected patients. Because there appears to be a lack of awareness of these enzymes, a study was conducted during 2001 to 2002 in which 6,421 consecutive, nonduplicate clinical isolates of aerobically growing gram-negative bacilli from patients at 42 intensive care unit (ICU) and 21 non-ICU sites across the United States were tested on-site for antibiotic susceptibility. From these isolates, 746 screenpositive isolates (11.6%) were referred to a research facility and investigated to determine the prevalence of ESBLs in all gram-negative isolates, transferable AmpC ␤-lactamases in Klebsiella pneumoniae, and carbapenemases in Enterobacteriaceae. The investigations involved phenotypic tests, isoelectric focusing, ␤-lactamase inhibitor studies, spectrophotometric assays, induction assays, and molecular analyses. ESBLs were detected only in Enterobacteriaceae (4.9% of all Enterobacteriaceae) and were found in species other than those currently recommended for ESBL testing by the CLSI (formerly NCCLS). These isolates occurred at 74% of the ICU sites and 43% of the non-ICU sites. Transferable AmpC ␤-lactamases were detected in 3.3% of K. pneumoniae isolates and at 16 of the 63 sites (25%) with no difference between ICU and non-ICU sites. Three sites submitted isolates that produced class A carbapenemases. No class B or D carbapenemases were detected. In conclusion, organisms producing ESBLs and transferable AmpC ␤-lactamases were widespread. Clinical laboratories must be able to detect important ␤-lactamases to ensure optimal patient care and infection control.

BackgroundDue to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC).MethodsThis study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10–14 days with PTZ, cefepime, or ertapenem.ResultsA total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC.ConclusionResults from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC.Trial registrationThe trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895)

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Extended-spectrum cephalosporin (ESC)-resistant Enterobacteriaceae is an increasingly important problem in both human and veterinary medicine. The aims of this study were to describe a comparative molecular characterization of Enterobacteriaceae carrying ESC resistance genes, encoding extended-spectrum β-lactamase (ESBL) and AmpC, isolated from human stool samples, rectal swabs from companion animals, and swabs from the environment of veterinarian hospitals in South Korea, and to examine their possible dissemination and transmission. The ESC resistance genes were identified by PCR and sequencing. Isolates with the predominant ESC resistance genes were assessed for their genetic relatedness by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. A total of 195 Escherichia coli and 41 Klebsiella pneumoniae isolates that exhibited ESC resistance were recovered on CHROMagar ESBL from human, companion animal, and the veterinary hospital environmental samples. In companion animals, most of the ESC resistance genes were bla CMY–2–like (26.4%), followed by bla CTX –M–55 (17.2%) and bla CTX–M–14 (16.1%), whereas bla CTX–M–15 (28.6%) was predominant in human samples. The epidemiological relatedness of isolates carrying ESC resistance genes, including 124 E. coli and 23 K. pneumoniae isolates carrying CMY-2-like, DHA-1-like, or/and CTX-M-type, were analyzed by PFGE. The pulsotypes of five E. coli isolates (three from dogs and two from humans) carrying bla CMY–2–like , which were attributed to sequence type 405, from different veterinary clinics showed >85% similarity. Our results indicate direct transmission and dissemination of ESC-resistant Enterobacteriaceae between humans and companion animals.

Five hundred four fecal specimens, collected between 2004 and 2006 from young children with acute diarrhea, were screened for rotavirus by ELISA with VP6-specific antibody. Of these samples, 394 (78.2%) were confirmed as group A rotavirus and they underwent G-and P typing using a combination of ELISA, RT-PCR, and sequence analysis methods. The dominant circulating G serotype was G1 (35.6%) followed by G3 (26.4%), G4 (14.7%), and G2 (11.9%). There was a low prevalence of G9 (1.0%) and of unusual G type rotavirus, in particular, G12 (0.5%) and G8 (0.3%). Of the P genotype rotavirus in circulation, P[8] (53.0%) was most common followed by P and G8P[8] were also found. Owing to the recent emergence of G8 and G12 rotavirus, the findings from this study are important since they provide new information concerning the local and global spread of rotavirus genotypes.

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We evaluated highly sensitive methods using boronic acid (BA) to detect extended-spectrum ␤-lactamase (ESBL) production. A total of 182 clinical isolates of Klebsiella spp. (n ‫؍‬ 118) and Escherichia coli (n ‫؍‬ 64) were analyzed: 62 harbored only ESBLs, 80 harbored both ESBLs and plasmid-mediated AmpC ␤-lactamases (pAmpCs), and 40 harbored only pAmpCs. The CLSI confirmatory test detected all isolates that produce only ESBLs but detected 85% of isolates that produce both enzymes. When a >5-mm increase in the zone diameter of either the cefotaxime (CTX) or the ceftazidime (CAZ) disk in the presence of both clavulanic acid (CA) and BA was considered to be a positive result, the test detected all isolates that harbor ESBLs (؎ pAmpCs) but showed frequent false-positive results (50%) for isolates that produce only pAmpCs. Meanwhile, when a >3-mm increase in the zone diameter of either the CTX/BA or the CAZ/BA disk in the presence of CA was considered to be a positive result, the test also detected all isolates that harbor ESBLs (؎ pAmpCs) and showed less frequent false-positive results (5%) in isolates that produce only pAmpCs. The latter new interpretive guideline has enhanced detection of ESBLs in clinical isolates of Klebsiella spp. and Escherichia coli and allowed detection of an ESBL even when potentially masked by a pAmpC.

Serosurveillance studies reveal the actual disease burden and herd immunity level in the population. In Seoul, Korea, a cross-sectional investigation showed 0.07% anti-severe acute respiratory syndrome coronavirus-2 antibody seropositivity among 1,500 outpatients of the university hospitals. Low seroprevalence reflects well-implemented social distancing. Serosurveillance should be repeated as the pandemic progresses.