BACKGROUND: Escherichia coli and Klebsiella pneumoniae clinical isolates producing CTX-M extendedspectrum β-lactamases (ESBLs) were assessed for antimicrobial resistance phenotypes varied by group of enzymes. METHODS: A total of 1,338 blood isolates, including 959 E. coli and 379 K. pneumoniae, were studied. All the strains were collected between January and July 2017 from eight general hospitals in South Korea. The species were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined by disk diffusion methods and ESBL phenotypes by double-disk synergy tests using disks containing cefotaxime, ceftazidime, cefepime, aztreonam, and clavulanic acid (CA). The genes for β-lactamases were identified by PCR and sequencing. RESULTS: Of total microbes, 31.6% (303/959) E. coli and 24.0% (91/379) K. pneumoniae were resistant to cefotaxime and 28.1% (269/959) E. coli and 20.1% (76/379) K. pneumoniae were CTX-M-type ESBL producers. Among the detected CTX-M ESBLs, 58.0% (156/269) in E. coli and 86.8% (66/76) in K. pneumoniae belonged to group 1, 46.8% (126/269) in E. coli and 14.5% (11/76) in K. pneumoniae were group 9. Ten E. coli and one K. pneumoniae isolates co-produced both groups of CTX-M ESBL. The group 1 CTX-M producers had a higher level of resistance to cefotaxime, ceftazidime, cefepime, and aztreonam and exhibited stronger synergistic activities when combined with CA compared to group 9. CONCLUSION: ESBL phenotypes differ by CTX-M ESBL group and phenotype testing with drugs including 4th generation cephalosporins and monobactams is critical for screening CTX-M-producers with better sensitivity.
Aztreonam ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Clavulanic Acid ; Diffusion ; Escherichia coli ; Hospitals, General ; Klebsiella pneumoniae ; Korea ; Mass Screening ; Mass Spectrometry ; Monobactams ; Phenotype ; Pneumonia ; Polymerase Chain Reaction

BACKGROUND: Recently Escherichia coli isolates with extended-spectrum beta-lactamase(ESBL) have been increased in Korea. ESBLs confer variable levels of resistance to cefotaxime, ceftazidime and other broad-spectrum cephalosporins as well as to monobactams such as aztreonam, but they have no detectable activity against cephamycins and carbapenems. The aim of this study was to characterize the ESBL produced by E. coli strains isolated from clinical specimens. METHODS: From March to July, 1998, a total of 93 clinical isolates of E. coli, which was produced ESBL, were collected from patients of the Asan Medical Center. The isolates flagged as ESBL producers by microbroth dilution antibiotic susceptibility test were confirmed by the double disk synergy test. Minimal inhibitory concentration(MIC) of beta-lactams were determined by agar dilution method. The presence of TEM, SHV or CMY-1 gene was determined by polymerase chain reaction. The types of beta-lactamase gene were determined by isoelectric focusing and nucleotide sequence analysis. RESULTS: Sixty-two strains carried plasmid-mediated TEM-52 gene, which sequence showed the substitution of 3 amino acids compared to that of TEM-1. Seventeen strains produced SHV-12, six strains produced SHV-2a, three strains produced TEM-52 and SHV-12, three strains produced TEM-52 and SHV-2a, and one strain produced SHV-2a and SHV-12. One out of twenty-seven strains of cefoxitin-resistant E. coli was confirmed to have CMY-1 beta-lactamase by PCR and nucleotide sequence analysis. CONCLUSIONS: TEM-52 was the most prevalent in E. coli isolates. The most common SHV-types of ESBL in Korea are SHV-12 and SHV-2a in E. coli isolates. In Korea, widespread use of oxyimino-cephalosporins in the hospitals has dramatically increased the prevalence of ESBL-producers in E. coli. Therefore, more prudent use of antibiotics is necessary to reduce the spread of these resistant organisms.
Agar ; Amino Acids ; Anti-Bacterial Agents ; Aztreonam ; Base Sequence ; beta-Lactamases* ; beta-Lactams ; Carbapenems ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Cephamycins ; Chungcheongnam-do ; Escherichia coli* ; Escherichia* ; Humans ; Isoelectric Focusing ; Korea ; Monobactams ; Polymerase Chain Reaction ; Prevalence

The overall prognosis of acute pyelonephritis is good, but the infections by extended spectrum beta-lactamase (ESBL) producing Escherichia coli (E.coli) cause poor responses to empirical antibiotic treatment, and consequently increase mortality. ESBL can hydrolyze the antibiotics with a beta-lactam ring and confer resistance to oxyimino-cephalosporins and monobactams. If the patient shows poor responses to empirical antibiotics or severe septic conditions, physicians must switch the antibiotics to other antibiotics covering resistant strains without delay. We report a case of acute pyelonephritis by extended-spectrum beta-lactamase producing E.coli in a 29-year-old woman who was empirically treated with oral ciprofloxacin as an initial treatment, but progressed to sepsis.
Adult ; Anti-Bacterial Agents ; beta-Lactamases ; Ciprofloxacin ; Escherichia ; Escherichia coli ; Female ; Humans ; Monobactams ; Prognosis ; Pyelonephritis ; Sepsis

The overall prognosis of acute pyelonephritis is good, but the infections by extended spectrum beta-lactamase (ESBL) producing Escherichia coli (E.coli) cause poor responses to empirical antibiotic treatment, and consequently increase mortality. ESBL can hydrolyze the antibiotics with a beta-lactam ring and confer resistance to oxyimino-cephalosporins and monobactams. If the patient shows poor responses to empirical antibiotics or severe septic conditions, physicians must switch the antibiotics to other antibiotics covering resistant strains without delay. We report a case of acute pyelonephritis by extended-spectrum beta-lactamase producing E.coli in a 29-year-old woman who was empirically treated with oral ciprofloxacin as an initial treatment, but progressed to sepsis.
Adult ; Anti-Bacterial Agents ; beta-Lactamases ; Ciprofloxacin ; Escherichia ; Escherichia coli ; Female ; Humans ; Monobactams ; Prognosis ; Pyelonephritis ; Sepsis

INTRODUCTION: Drug allergies are often self-reported but of unknown accuracy. We carried out a prospective study to examine the utility and safety of formal allergology evaluation, and to identify factors associated with accurate drug allergy labels. METHOD: All patients who underwent drug allergy evaluation in our clinic during the study period were recruited. Baseline demographics, characteristics of index hypersensitivity reaction and outcomes of evaluation were recorded. RESULTS: A total of 331 patients from March 2019 to June 2021 completed drug allergy evaluation to index drugs of concern. There were 123 (37%) male patients, and the mean age was 49 years (standard deviation 17). There were 170 beta-lactam antibiotics, 53 peri-operative drugs, 43 others, 38 non steroidal anti-inflammatory drugs, and 27 non-beta-lactam antibiotic evaluations. Index reaction occurred within 5 years in 165 (50%) patients, with latency of less than 4 hours in 125 (38%) patients. The most common index reactions were rash, angioedema and urticaria. There were 57 (17%) evaluations stratified as low risk, 222 (67%) moderate risk, and 52 (16%) high risk based on multidisciplinary consensus. Allergy label was found to be false (negative drug evaluation) in 248 (75%) patients, while 16/237 (7%) skin tests, 44/331 (13%) in-clinic graded challenge, and 23/134 (17%) home prolonged challenges were positive (true drug allergy). The most common evaluation reactions were rash and urticaria. No cases of anaphylaxis were elicited. CONCLUSION Seventy-five percent of drug allergy labels are inaccurate. Risk-stratified, protocolised allergy evaluation is safe. Prolonged drug challenge increases the sensitivity of drug allergy evaluation and should therefore be performed when indicated.
Humans ; Male ; Middle Aged ; Female ; Prospective Studies ; Drug Hypersensitivity/epidemiology* ; Exanthema ; Urticaria ; Monobactams

Metallo-beta-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all beta-lactam antibiotics except monobactams. There are various types of metallo-beta-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron-encoded metallo-beta-lactamase (VIM), Sao Paulo metallo-beta-lactamase (SPM), Germany imipenemase (GIM), New Delhi metallo-beta-lactamase (NDM), Florence imipenemase (FIM). Each MBL gene is located on specific genetic elements including integrons, transposons, plasmids, or on the chromosome, in which they carry genes encoding determinants of resistance to carbapenems and other antibiotics, conferring multidrug resistance to P. aeruginosa. In addition, these genetic elements are transferable to other Gram-negative species, increasing the antimicrobial resistance rate and complicating the treatment of infected patients. Therefore, it is essential to understand the epidemiology, resistance mechanism, and molecular characteristics of MPPA for infection control and prevention of a possible global health crisis. Here, we highlight the characteristics of MPPA.
Anti-Bacterial Agents ; Carbapenems ; Drug Resistance, Multiple ; Epidemiology* ; Germany ; Humans ; Infection Control ; Integrons ; Monobactams ; Plasmids ; Pseudomonas aeruginosa*

PURPOSE: The incidence of community-acquired urinary tract infection (UTI) due to extended-spectrum beta-lactamase producing Escherichia coli (ESBL(+) E. coli) has increased worldwide. ESBL causes resistance to various types of the newer beta-lactam antibiotics, including the expanded spectrum cephalosporins and monobactams. We aimed to investigate the severity of UTI and associated genitourinary malformations in children with febrile UTI caused by ESBL(+) E. coli. METHODS: We retrospectively reviewed the medical records of 290 patients diagnosed as febrile UTI caused by E. coli between January 2008 and October 2010 at Korea University Medical center. We classified the patients into two groups with ESBL(+) and ESBL(-) E. coli group according to the sensitivity of urine culture. Fever duration, admission period, white blood cell (WBC) counts and C-reactive protein (CRP) in peripheral blood, the presence of hydronephrosis, cortical defects, vesicoureteral reflux (VUR) and renal scar were compared between the two groups. RESULTS: Patients with ESBL(+) E. coli were 32, and those with ESBL(-) E. coli were 258. If we excluded those tested with a sterile urine bag, patients with ESBL(+) E. coli were 22, and those with ESBL(-) E. coli were 212. Whether the results of sterile urine bag tests were included or not, there was no significant difference in all parameters between the two groups statistically. CONCLUSION: Our data shows that ESBL(+) E. coli may not be related to the severity of UTI and associated genitourinary malformations.
Academic Medical Centers ; Anti-Bacterial Agents ; beta-Lactamases ; C-Reactive Protein ; Cephalosporins ; Child ; Cicatrix ; Escherichia ; Escherichia coli ; Fever ; Humans ; Hydronephrosis ; Incidence ; Korea ; Leukocytes ; Medical Records ; Monobactams ; Retrospective Studies ; Urinary Tract ; Urinary Tract Infections ; Vesico-Ureteral Reflux

BACKGROUND: The prevalence of extended-spectrum -lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli has been increased in Korea, but the testing and reporting ESBL-mediated resistance remains unclear. We undertook a study to evaluate the method to screen isolates of ESBL-producing K. pneumoniae and E. coli using cefpodoxime disk. METHODS: Fifty-eight strains of K. pneumoniae and 28 strains of E. coli were tested for production of ESBLs by the double disk synergy test. Susceptibility to cefpodoxime, ceftazidime, cefotaxime, and aztreonam was determined by disk diffusion method. RESULTS: All strains that produced ESBLs were resistant to cefpodoxime, whereas those that not produced ESBLs were susceptible (97%) to this agents. The disk diffusion test exhibited 100% sensitivity and 97% specificity when NCCLS conventional interpretive criteria were used. All other oxyimino- -lactam agents tested were inferior discriminators between the two groups of organisms. When NCCLS ESBL interpretive criteria were used, the disk diffusion test using cefpodoxime exhibited 100% sensitivity and 83% specificity. CONCLUSIONS: Routine disk diffusion susceptibility test with cefpodoxime disk (10g) can be used to detect strains of ESBL-producing K. pneumoniae and E. coli without include supplemental testing for ESBL production.
Aztreonam ; Cefotaxime ; Ceftazidime ; Diffusion ; Escherichia coli* ; Escherichia* ; Klebsiella pneumoniae* ; Klebsiella* ; Korea ; Pneumonia ; Prevalence ; Sensitivity and Specificity

BACKGROUND/AIMS: The inhibitory effects of the combination of beta-lactam with ciprofloxacin or amikacin against clinical isolates of multidrug-resistant Pseudomonas aeruginosa were evaluated. METHODS: This study examined ten isolates with variable levels of resistance to ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, and amikacin. The efficacy of the combined antibiotics was studied using a checkerboard method or in vitro killing assay. RESULTS: The combination of ceftazidime, cefepime, aztreonam, piperacillin-tazobactam, or meropenem with amikacin showed synergistic effects for all of the strains regardless of the minimum inhibitory concentration (MIC) of amikacin, but combination with ciprofloxacin showed a synergistic effect for the isolate with a low MIC of ciprofloxacin by the checkerboard method. The isolates with a high MIC of ciprofloxacin showed an indifferent effect in combination with beta-lactam and ciprofloxacin. The in vitro killing assay showed that meropenem with ciprofloxacin acted synergistically for the isolates with a MIC of 16 microgram/mL of ciprofloxacin. However, amikacin showed synergistic effects with meropenem for the isolates with high-level resistance against amikacin, i.e., up to an MIC of 128 microgram/mL. Contrary to the checkerboard method results, no synergy was observed for the combination of ceftazidime/piperacillin-tazobactam and amikacin. CONCLUSIONS: Meropenem with amikacin can be the first choice for infections caused by multidrug-resistant P. aeruginosa when the level of resistance is not known.
Amikacin ; Anti-Bacterial Agents ; Aztreonam ; Ceftazidime ; Cephalosporins ; Ciprofloxacin ; Homicide ; Microbial Sensitivity Tests ; Pseudomonas ; Pseudomonas aeruginosa ; Thienamycins

An increasing prevalence of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) causes a serious therapeutic problem in clinical setting. This study investigated the antimicrobial susceptibility, resistance mechanisms against aminoglycosides, and molecular epidemiology of 76 blood isolates of P. aeruginosa from two Korean hospitals. Thirty-four isolates were susceptible to all 13 antimicrobial agents tested, whereas 28 isolates showed a MDR or extensively drug-resistant phenotype. There was a significant difference in resistance rates of P. aeruginosa isolates against aztreonam, piperacillin-tazobactam, imipenem, meropenem, ciprofloxacin, and norfloxacin between two hospitals. Genes for aminoglycoside-modifying enzymes (AMEs), including aphA6 (n = 14), aadB (n = 11), aacA4 (n = 8), and aphA1 (n = 1), and 16S rRNA methylase armA (n = 6) were detected in 26 P. aeruginosa isolates resistant to aminoglycosides. There was no significant difference in carriage of genes for AME and 16S rRNA methylase between two hospitals, but aacA4 and aphA1 were specifically detected in P. aeruginosa isolates from one hospital. Seventy-six P. aeruginosa isolates were classified into 55 pulsotypes at similarity value of 0.85, and 31 and 24 pulsotypes were specifically detected in each hospital. This study demonstrates that differences in antimicrobial susceptibility of P. aeruginosa isolates between two hospitals are possibly due to the presence of diverse clones specific in each hospital.
Aminoglycosides ; Anti-Infective Agents ; Aztreonam ; Ciprofloxacin ; Clone Cells ; Imipenem ; Molecular Epidemiology ; Norfloxacin ; Phenotype ; Prevalence ; Pseudomonas aeruginosa* ; Pseudomonas*