cefotaxime and Klebsiella-Infections

In a prospective, open clinical study, 50 urological patients with acute pyelonephritis were treated with the oral cephalosporin cefixime. The medication (2 x 200 mg/day) was given for seven to ten days. Clinical, bacteriological as well as hematological examinations were carried out prior to, during and immediately after therapy. A late check-up was performed five to nine days after the end of therapy. 46 of the 50 cases were evaluable for efficacy, and all 50 patients were included in safety evaluation. The most frequent pathogens isolated prior to therapy were Escherichia coli (34 times), Proteus mirabilis (six times), Klebsiella pneumoniae (twice) and coagulase-negative staphylococci (twice). Immediately after the end of therapy the pathogens were eradicated in 44 (97.5%) patients. At the late check-up the urine was sterile in 29 (63%) patients. A relapse was observed in 11 patients, a reinfection in four and the initially isolated pathogens had persisted in two. Immediately after the end of therapy 44 (95.7%) patients were clinically cured and two patients had improved. At the late check-up 41 patients were classified as clinically cured, three showed improvement, and two improvement with relapse. Adverse reactions (one case nausea and exanthem, and one case of meteorism) occurred in two patients. No changes in the blood counts or in the liver and kidney functions were observed. In the study described here cefixime proved to be an effective and well tolerated antibiotic for the treatment of upper urinary tract infections; it is of particular interest that 16 of the 50 patients presented with underlying disease favoring infection.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Body Temperature; Cefixime; Cefotaxime; Drug Tolerance; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Leukocyte Count; Male; Middle Aged; Prospective Studies; Proteus Infections; Pyelonephritis; Recurrence; Staphylococcal Infections

One hundred six patients with acute, uncomplicated lower urinary tract infections participated in a randomized study that compared cefixime (one 400-mg tablet once daily) with trimethoprim (160 mg)/sulfamethoxazole (800 mg) (one tablet every 12 hours). Two cefixime recipients and 3 patients given trimethoprim/sulfamethoxazole had courses that were not evaluable for efficacy. At five to nine days post-therapy, 98 percent of the patients in each treatment group had clinical cure and bacteriologic eradication. At four to six weeks post-therapy, 87 percent (34/39) of the cefixime-treated patients and 83 percent (33/40) of those given trimethoprim/sulfamethoxazole had clinical cure and 90 percent (35/39) and 93 percent (37/40) of the patients in the respective treatment groups had bacteriologic eradication. Adverse clinical experiences or changes in the results of laboratory tests were few. Thus, a once-daily dose of cefixime was as safe and as effective as a twice-daily regimen of trimethoprim/sulfamethoxazole.

Topics: Anti-Infective Agents, Urinary; Cefixime; Cefotaxime; Drug Administration Schedule; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Randomized Controlled Trials as Topic; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Ceftriaxone effectively inhibited 332 out of 452 (73.45%) bacterial strains in vitro tests. 291 out of 365 (79.69%) gram negative and 41 out of 87 (47.12%) gram positive strains were inhibited. The tests showed ceftriaxone to be more effective than cephalothin, cephotaxime, cephuroxime, cephamandol and cephoxitin. Kinetic tests showed that cephtriaxone has a plasmatic half life of 7.25 hrs. 24 hours after administration of a 1000 mg venous bolus the drug was still present in the blood. Urinary elimination over a 24 hr. period amounted to means 486.8 mg (48.68%). The drug has liquor transfer capacity. 37 of the 38 patients treated showed complete clinical or clinicobacteriological cure. Improvement was noted in the 38th.

Topics: Adolescent; Adult; Aged; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Clinical Trials as Topic; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Humans; Kinetics; Klebsiella Infections; Male; Meningitis; Middle Aged; Respiratory Tract Infections; Staphylococcal Infections; Streptococcal Infections

The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in human volunteers. The combination of cefotaxime plus amikacin was more synergistic in vitro than the others against the Enterobacteriaceae tested, and the combination of azlocillin plus amikacin was more synergistic against Pseudomonas aeruginosa and Staphylococcus aureus. Survival of neutropenic mice infected with Escherichia coli and Klebsiella pneumoniae, respectively, was greater with azlocillin plus amikacin (24 of 40 and 11 of 40) and with cefotaxime plus amikacin (21 of 40 and 17 of 40) than with azlocillin plus cefotaxime (22 of 40 and 3 of 40; P less than 0.05). Median serum bactericidal activity in volunteers receiving these antibiotics alone and in combination was greater than or equal to 1:8 with most agents and with all combinations tested against 10 strains each of E. coli, K. pneumoniae, P. aeruginosa, and S. aureus. These data suggest that clinical trials with combinations of azlocillin or cefotaxime plus amikacin deserve further study in febrile neutropenic patients.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Azlocillin; Cefotaxime; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Klebsiella; Klebsiella Infections; Mice; Mice, Inbred BALB C; Penicillins; Pseudomonas aeruginosa; Serratia; Staphylococcus aureus

The aim of this study was to understand the prevalence of antibiotic resistance in Klebsiella pneumoniae present in the population in Bergen city, Norway using city-scale sewage-based surveillance, as well as the potential spread of K. pneumoniae into the marine environment through treated sewage. From a total of 30 sewage samples collected from five different sewage treatment plants (STPs), 563 presumptive K. pneumoniae isolates were obtained on Simmons Citrate Agar with myo-Inositol (SCAI) plates, and 44 presumptive K. pneumoniae isolates on SCAI plates with cefotaxime. Colistin resistance was observed in 35 isolates, while cefotaxime resistance and tigecycline resistance was observed in only five isolates each, out of 563 presumptive K. pneumoniae isolates. All 44 isolates obtained on cefotaxime-containing plates were multidrug-resistant, with 25% (n = 11) showing resistance against tigecycline. Clinically important acquired antibiotic resistance genes (ARGs), like bla

Topics: Anti-Bacterial Agents; Cefotaxime; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sewage; Tigecycline; Wastewater-Based Epidemiological Monitoring

Bacterial infections in COVID-19 patients, especially those caused by multidrug-resistant gram-negative strains, are associated with increased morbidity, hospital stay and mortality. However, there is limited data on the epidemiology of extended-spectrum β-lactamase (ESBL)-producing bacteria in COVID-19 patients. Here, we assessed the prevalence and the factors associated with ESBL-producing gram-negative bacterial (GNB) infections among severely ill COVID-19 patients admitted in Kenyatta National Hospital (KNH), Kenya.. We adopted a descriptive cross-sectional study design for patients admitted between October 2021 and February 2022, purposively recruiting 120 SARS-CoV- 2 infected participants based on clinical presentation. Demographics and clinical characteristics data were collected using structured questionnaires and case report forms. Clinical samples were collected and analyzed by standard microbiological methods in the KNH Microbiology laboratory and the Centre for Microbiology Research, Kenya Medical Research Institute.. GNB infections prevalence was 40.8%, majorly caused by ESBL-producers (67.3%) predominated by Klebsiella pneumoniae (45.5%). Generally, 73% of the ESBL producers harboured our target ESBL genes, mainly CTX-M-type (59%, 17/29) in K. pneumoniae (76.9%, 20/26). GNB harbouring TEM-type (83%, 10/12) and SHV-type (100%, 7/7) genes showed ESBLs phenotypes and inhibitor resistance, mainly involving clavulanate, but most of them remained susceptible to tazobactam (60%, 6/10). SHV-type genes carrying ESBL producers showed resistance to both cefotaxime (CTX) and ceftazidime (CAZ) (K. pneumoniae), CAZ (E. coli) or CTX (E. cloacae complex and K. pneumoniae). About 87% (20/23) of isolates encoding CTX-M-type β-lactamases displayed CTX/ceftriaxone (CRO) resistance phenotype. About 42% of isolates with CTX-M-type β-lactamases only hydrolyzed ceftazidime (CAZ). Isolates with OXA-type β-lactamases were resistant to CTX, CAZ, CRO, cefepime and aztreonam. Patients with comorbidities were 10 times more likely to have an ESBL-producing GNB infection (aOR = 9.86, 95%CI 1.30 - 74.63, p = 0.003).. We report a high prevalence of ESBL-GNB infections in severely ill COVID-19 patients, predominantly due to Klebsiella pneumoniae harbouring CTX-M type ESBL genes. The patient's underlying comorbidities increased the risk of ESBL-producing GNB infection. In COVID-19 pandemic, enhanced systematic and continuous surveillance of ESBL-producing GNB, strict adherence to infection control measures and antimicrobial stewardship policies are warranted in the current study setting.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; COVID-19; Cross-Sectional Studies; Escherichia coli; Escherichia coli Infections; Hospitals; Humans; Kenya; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pandemics; Referral and Consultation

In this study, an IncI1 plasmid encoding resistance to both cefotaxime and azithromycin was recovered from a clinical Klebsiella pneumoniae strain. The azithromycin resistance was confirmed to be mediated by the

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Cefotaxime; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gene Transfer, Horizontal; Humans; Klebsiella Infections; Klebsiella pneumoniae; Methyltransferases; Microbial Sensitivity Tests; Plasmids; Salmonella

Klebsiella pneumoniae is a major pathogen implicated in nosocomial infections. Extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates are a public health concern. We aim to characterize the type of β-lactamases and the associated resistance mechanisms in ESBL-producing K. pneumoniae isolates obtained from blood cultures in a Portuguese hospital, as well as to determine the circulating clones. Twenty-two cefotaxime/ceftazidime-resistant (CTX/CAZR) K. pneumoniae isolates were included in the study. Identification was performed by MALDI-TOF MS and the antimicrobial susceptibility testing by disk-diffusion. The screening test for ESBL-production was performed and ESBL-producer isolates were further characterized. The presence of different beta-lactamase genes (blaCTX-M, blaSHV, blaTEM, blaKPC, blaNDM, blaVIM, blaOXA-48, blaCMY-2, blaDHA-1, blaFOX, blaMOX, and blaACC) was analyzed by PCR/sequencing in ESBL-producer isolates, as well as the presence of other resistance genes (aac(6')-Ib-cr, tetA/B, dfrA, qnrA/B/S, sul1/2/3) or integron-related genes (int1/2/3). Multilocus-sequence-typing (MLST) was performed for selected isolates. ESBL activity was detected in 12 of the 22 CTX/CAZR K. pneumoniae isolates and 11 of them carried the blaCTX-M-15 gene (together with blaTEM), and the remaining isolate carried the blaSHV-106 gene. All the blaCTX-M-15 harboring isolates also contained a blaSHV gene (blaSHV-1, blaSHV-11 or blaSHV-27 variants). Both blaSHV-27 and blaSHV-106 genes correspond to ESBL-variants. Two of the CTX-M-15 producing isolates carried a carbapenemase gene (blaKPC2/3 and blaOXA-48) and showed imipenem resistance. The majority of the ESBL-producing isolates carried the int1 gene, as well as sulphonamide-resistance genes (sul2 and/or sul3); the tetA gene was detected in all eight tetracycline-resistant isolates. Three different genetic lineages were found in selected isolates: ST348 (one CTX-M-15/TEM/SHV-27/KPC-2/3-producer isolate), ST11 (two CTX-M-15/TEM/SHV-1- and CTX-M-15-TEM-SHV-11-OXA-48-producer isolates) and ST15 (one SHV-106/TEM-producer isolate). ESBL enzymes of CTX-M-15 or SHV-type are detected among blood K. pneumoniae isolates, in some cases in association with carbapenemases of KPC or OXA-48 type.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Sepsis; Sequence Analysis, DNA

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biofilms; Cats; Cefotaxime; Dogs; Drug Resistance, Multiple, Bacterial; Goats; India; Klebsiella; Klebsiella Infections; Livestock; Pets; Sheep

Klebsiella pneumoniae is an important multi-drug-resistant Gram-negative pathogen, associated with nosocomially acquired infections. This study aimed to determine the genotypic and phenotypic characterization of Klebsiella pneumoniae isolates and to correlate the antibiotic resistance with the presence of virulence genes revealed by molecular genotypic testing in Riyadh, Saudi Arabia.. About 23 Klebsiella pneumoniae isolates were collected from various specimen types. Identification of the organisms was carried out. Antimicrobial susceptibility performed against 12 antibiotics. The DNA was isolated and purified then genotypic confirmation was done through polymerase chain reactions (PCR) to detect TEM, SHV, CTX-M, IMP and KPC genes. PCR products were sequenced and aligned with GenBank sequences.. Out of 23 isolates of K. pneumoniae, the majority (43.5%) was from tracheal aspirate. The percentage of females (65.2%) was more than males (34.8%). The highest isolates prevalence was found in the age group of >58 (39.1%). About 100% of isolates were resistant to cefotaxime, ceftriaxone, ceftazidime, cefepime and ampicillin and 91.3% were sensitive to amikacin and Imipenem. Most isolates were SHV-9 gene positive (52.2%). It was found that tested isolates had 99-100% similarity when compared to GenBank sequences.. There was a preponderance of SHV-9 gene which suggests dissemination of the gene in the tested isolates.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; DNA, Bacterial; Female; Genetic Variation; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Saudi Arabia; Virulence

Topics: Anti-Bacterial Agents; Bacteremia; Cefotaxime; Child; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pulmonary Embolism; Tomography, X-Ray Computed

Bacterial pathogens producing CTX-M beta-lactamases are emerging around the world as a source of resistance to oxyimino cephalosporins such as cefotaxime. In this study, we have investigated the prevalence of blaCTX-M genes among clinical isolates of Escherichia coli and Klebsiella pneumoniae. Of the double-disk synergy test-positive E. coli (n = 94) and Kl. pneumoniae (n = 73) strains isolated during the study period, 41 (44·08%) E. coli and 32 (43·24%) Kl. pneumoniae isolates were found to be positive for blaCTX-M genes. Twenty-two integrons (13 for E. coli and 9 for Kl. pneumoniae) were detected whose sizes ranged from 600 bp to 1·5 kb. All these integrons were found to be of Class1 type and were invariably PCR positive for int1 and sul1 genes. Marker transfer experiments demonstrated plasmid-mediated transfer of cefotaxime and ceftazidime resistance markers. In addition, analysis of the enterobacterial repetitive intergenic consensus (ERIC)-PCR typing of the blaCTX-M -carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection.. A high frequency of blaCTX-M -resistant marker has been found in Escherichia coli and Klebsiella pneumoniae isolates of clinical origin. Analysis of the ERIC-PCR typing of the blaCTX-M -carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection.

Topics: beta-Lactamases; Cefotaxime; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Integrons; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Molecular Typing; Prevalence

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Aztreonam; Bacterial Proteins; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Prospective Studies; Young Adult

Generation of extended- spectrum β- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics. Combined antibiotics prove to be a relatively effective method of controlling such resistant strains. Some of Chinese herbal active ingredients are known to have synergistic antibacterial effects. This study is aimed to investigate synergistic effects of Chinese herbal active ingredients with cefotaxime on the extended- spectrum β- lactamase positive strains of Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing experimental evidence for clinical application of antimicrobial drugs.. For total sixteen strains including fifteen strains of cefotaxime resistant K. pneumoniae and one extended- spectrum β- lactamase positive standard strain, the synergy rates of cefotaxime with baicalein, matrine, and clavulanic acid were 56.3 %, 0 %, and 100 %, respectively. The fractional inhibitory concentration index of combined baicalein and cefotaxime was correlated with the percentage decrease of cefotaxime MIC of all the strains (r = -0.78, p <0.01). In the group of synergy baicalein and cefotaxime, the transcribed mRNA level of CTX-M-1 after treatment of baicalein was decreased significantly (p <0.05). Moreover, the CTX-M-1 mRNA expression percentage inhibition (100 %, 5/5) was significantly higher than non- synergy group (25 %, 1/4) (p <0.05).. Our study demonstrated that baicalein exhibited synergistic activity when combined with cefotaxime against some of extended- spectrum β- lactamases positive K. pneumoniae strains by inhibiting CTX-M-1 mRNA expression. However, no direct bactericidal or bacteriostatic activity was involved in the synergistic action. Baicalein seems to be a promising novel effective synergistic antimicrobial agent.

Topics: Alkaloids; Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Clavulanic Acid; DNA, Bacterial; Drug Synergism; Drugs, Chinese Herbal; Escherichia coli Proteins; Flavanones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Matrines; Microbial Sensitivity Tests; Quinolizines; RNA, Messenger

Drug-resistant Klebsiella pneumoniae, especially extended-spectrum β-lactamase (ESBL)- and/or AmpC β-lactamase-producing strains, is an emerging problem worldwide. However, few data focusing on drug susceptibility of K. pneumoniae from community is available. In this study, we analyzed 1016 K. pneumoniae isolates from outpatients or those visiting emergency rooms collected during 2002-2012 from Taiwan Surveillance of Antimicrobial Resistance program. Significantly decreased susceptibilities to 3

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Ciprofloxacin; Genetic Variation; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Phylogeny; Population Surveillance; Taiwan; Urine; Young Adult

Community-acquired bacterial meningitis due to Klebsiella pneumoniae has mainly been described in Southeast Asia and has a poor prognosis. Severe invasive infections caused by K. pneumoniae, including meningitis, are often due to hypervirulent strains (hvKP), which are characterized by capsular serotypes K1 and K2, a gene responsible for hypermucoviscosity, and the cluster for synthesis of the siderophore aerobactin.. A 55 year old man with a history of essential hypertension, benign prostate hyperplasia, hyperlipidemia, obstructive sleep apnea, and chronic alcoholism was admitted for meningitis due to Klebsiella pneumoniae with a wild-type susceptibility profile. Its genomic features were consistent with a capsular K2 strain belonging to clonal group 86 (CG86) displaying the large virulence of Klebsiella plasmid (pLVPK) with heavy metal resistance gene clusters, aerobactin, rmpA.. This is the first case of community-acquired meningitis caused by a hypervirulent strain of hvKP ever reported in the Caribbean.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Cefotaxime; Community-Acquired Infections; Genotype; Guadeloupe; Humans; Hydroxamic Acids; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Middle Aged; Plasmids; Serogroup; Virulence Factors

Topics: Aged; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Diabetes Mellitus; Fermentation; Glucose; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver; Liver Abscess; Male; Taiwan; Tomography, X-Ray Computed

CTX-M-15 is the dominant type of extended-spectrum β-lactamase in clinical isolates. This enzyme constitutes the most widespread enzymes in Tunisia. In this study, we were interested to understand the causes of the evolutionary success of CTX-M-15 in a Tunisian university hospital.. A total of of 72 cefotaxime-resistant Enterobacteriaceae were isolated from newborn patients at the hospital Taher sfar Mahdia in Tunisia and characterized their genetic support by means of molecular techniques.. Isolates were clustered into various clonal groups, although most isolates belonged to sequence types ST39 (Klebsiella pneumoniae) and ST131 (Escherichia coli). F replicons (FIA, FIB, and FII) were the most frequently detected replicon types in our collection (91.66%).. This is the first report of QnrB- and CTX-M-15-encoding large IncF-type conjugative plasmids in Tunisia.

Topics: Academic Medical Centers; beta-Lactamases; Cefotaxime; Drug Resistance, Bacterial; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Evolution, Molecular; Genetic Variation; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Plasmids; Tunisia

The objective of this study was to characterize plasmids coharboring 16S rRNA methylases, blaCTX-M and virulence-associated genes in Escherichia coli and Klebsiella pneumoniae isolates from chickens in China. A total of 32 positive transconjugants exhibited coresistance to amikacin and cefotaxime in E. coli (24/281) and K. pneumoniae (8/93), and were identified by conjugation experiments and S1-pulsed-field gel electrophoresis. Polymerase chain reaction amplification assay detecting resistance genes showed that rmtB or armA gene accompanied with different blaCTX-M genes coexisted on 32 transferred plasmids. The blaCTX-M-98b gene was identified in chicken-derived E. coli and K. pneumoniae for the first time. The association between resistance genes and virulence genes was observed in the transferred plasmids; 68.8% (22/32) transferred resistance plasmids coharboring various virulence genes including traT, iutA, fyuA, msbB, and vagC genes with diverse proportions. Genetic stability tests revealed that 93.8% (30/32) transferred plasmids continued to exist in the host strain after continuous passage of 30 times in 15 days. Furthermore, 87.5% (28/32) conjugants showed no significant differences in growth rates compared with E. coli J53. Results of the growth competition assay showed that conjugants have low fitness cost, which indicated that there were no obvious negative effects on the host's growth. The combination of blaCTX-M-98b-rmtB-traT on 85-kb transferred IncF plasmids in E. coli, and blaCTX-M-14-rmtB-traT on 95-kb transferred IncF plasmids in K. pneumoniae were first identified in this study. These features of plasmids may contribute to the successful spread of resistance and virulence among pathogens of different sources and geographical origins.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Bacterial Proteins; Bacteriocin Plasmids; beta-Lactamases; Cefotaxime; Chickens; China; Conjugation, Genetic; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Klebsiella Infections; Klebsiella pneumoniae; Methyltransferases; Microbial Sensitivity Tests; Polymerase Chain Reaction; RNA, Ribosomal, 16S; tRNA Methyltransferases; Virulence Factors

Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae, can be conferred by a large number of different acquired resistance genes, although it appears that relatively few dominate. A previous survey of Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia, revealed that a limited set of genes could reliably predict resistance to third-generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration of ≥ 2 μg/mL from China and Singapore, with significantly higher resistance rates than Australia, as well as the USA. Few targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and gentamicin (47/51; 92%). The gene types detected here are consistent with previous surveys in similar countries with similar resistance rates, where the majority of 3GC resistance can be explained by blaCTX-M genes. This study identified a limited set of genes capable of predicting resistance to 3GC and aminoglycoside antibiotics and implies a restriction in the global resistance gene pool that can be exploited for diagnostic purposes.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Ceftriaxone; China; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Genes, Bacterial; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Singapore; United States

In 2009, CTX-M Enterobacteriaceae and Salmonella isolates were recovered from a UK pig farm, prompting studies into the dissemination of the resistance and to establish any relationships between the isolates.. PFGE was used to elucidate clonal relationships between isolates whilst plasmid profiling, restriction analysis, sequencing and PCR were used to characterize the CTX-M-harbouring plasmids.. Escherichia coli, Klebsiella pneumoniae and Salmonella 4,5,12:i:- and Bovismorbificans resistant to cefotaxime (n = 65) were recovered and 63 were shown by PCR to harbour a group 1 CTX-M gene. The harbouring hosts were diverse, but the group 1 CTX-M plasmids were common. Three sequenced CTX-M plasmids from E. coli, K. pneumoniae and Salmonella enterica serotype 4,5,12:i:- were identical except for seven mutations and highly similar to IncI1 plasmid ColIb-P9. Two antimicrobial resistance regions were identified: one inserted upstream of yacABC harbouring ISCR2 transposases, sul2 and floR; and the other inserted within shfB of the pilV shufflon harbouring the ISEcp1 transposase followed by blaCTX-M-1.. These data suggest that an ST108 IncI1 plasmid encoding a blaCTX-M-1 gene had disseminated across multiple genera on this farm, an example of horizontal gene transfer of the blaCTX-M-1 gene.

Topics: Animals; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Cefotaxime; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Gene Transfer, Horizontal; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Plasmids; Salmonella enterica; Salmonella Infections, Animal; Sequence Analysis, DNA; Swine; United Kingdom

Antibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistant Klebsiella pneumoniae strain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 10(6) CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX (P < 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced (P < 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.

Topics: Administration, Oral; Adsorption; Animals; Anti-Bacterial Agents; Area Under Curve; beta-Lactam Resistance; Cefotaxime; Charcoal; Colony Count, Microbial; Drug Synergism; Feces; Female; Intestines; Klebsiella Infections; Klebsiella pneumoniae; Mice

The aim of this study was to investigate the prevalence and types of plasmid-mediated AmpC (pAmpC) beta-lactamase enzymes in Escherichia coli and Klebsiella pneumoniae strains isolated from blood cultures of hospitalized patients in Dokuz Eylul University Hospital between 2007 and 2012. A total of 261 isolates which consisted of 184 E.coli (70.5%) and 77 K.pneumoniae (29.5%) were included in the study. All isolates were resistant to cefotaxime and/or ceftazidime but susceptible to imipenem. Cefoxitin resistance was investigated as an indicator of AmpC type enzymes. A total of 57 (21.8%) isolates which were cefoxitin-resistant (32 E.coli, 25 K.pneumoniae), were screened for pampC genes by a multiplex polymerase chain reaction (PCR) assay. Additionally, 10 of each cefoxitin susceptible isolates per year were chosen randomly and screened by the same PCR assay to detect the presence of ACC enzymes, which can not hydrolyze cefoxitin. Positive PCR results were confirmed by sequence analysis. Plasmid analysis and macrorestriction analysis were performed for pampC-positive isolates. The presence of pAmpC enzymes has been shown in 9.4% (3/32) of cefoxitin-resistant E.coli, and 8% (2/25) of cefoxitin-resistant K.pneumoniae strains. It was noted that there were no strains producing this enzyme isolated in 2007 and 2008, however the prevalence of pAmpC was detected as 1.6% in 2009 (one ACT-1 producing K.pneumoniae), increasing to 4.8% in 2011 (one ACT-1 producing K.pneumoniae) and 6.4% in 2012 (three CMY-2 producing E.coli). These enzymes were found to be carried on 81 kb size plasmids in K.pneumoniae isolates and on a 9 kb size plasmid in E.coli isolates. Macrorestriction analysis indicated that two of the three CMY-2 producing E.coli had the same PFGE (Pulsed-field gel electrophoresis) pattern. If these two strains are considered as identical, it can be concluded that the prevalence of pAmpC was low in the strains isolated between 2007-2012 (4/261; 1.5%) in our institution. On the other hand, the increasing prevalence of pAmpC in 2011 and 2012 should be considered as a warning for the implementation of infection control measures and monitorization of the prevalence in order to prevent the dissemination of pAmpC. As far as the current literature is concerned, this is the first study that demonstrated the presence of the ACT-1 enzyme in K.pneumoniae isolates in Turkey.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Cefotaxime; Cefoxitin; Ceftazidime; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Plasmids

We investigated the performance of cefotaxime for the detection of extended-spectrum β-lactamase (ESBL) or plasmid-mediated AmpC β-lactamase (pAmpC) and the clinical characteristics of cefotaxime-non-susceptible Escherichia coli or Klebsiella pneumoniae (CTXNS-EK) bacteraemia. All of the consecutive bloodstream isolates between 2005 and 2010 in a Japanese university hospital were characterised using polymerase chain reaction (PCR). Risk factors and outcomes of CTXNS-EK were analysed by multivariate logistic regression analysis. We identified 58 CTXNS-EK (15.6%) from 249 E. coli and 122 K. pneumoniae. Cefotaxime with a minimum inhibitory concentration (MIC) of >1 μg/mL had a sensitivity of 98.3% and a specificity of 99.7% for the detection of ESBL or pAmpC. CTXNS-EK had increased from 4.5% in 2005 to 23% in 2009. Risk factors for CTXNS-EK were previous isolation of multidrug-resistant bacteria, use of oxyimino-cephalosporins or fluoroquinolones, and high Sequential Organ Failure Assessment (SOFA) score. Patients with CTXNS-EK bacteraemia less frequently received appropriate empirical therapy than patients with cefotaxime-susceptible EK bacteraemia (81% vs. 97%, p<0.001) and died within 30 days (21% vs. 5%, p=0.001). Using the current breakpoints of the Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST), cefotaxime alone can identify ESBL or pAmpC producers. CTXNS-EK is an important and increasingly prevalent bacteraemia pathogen.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefotaxime; Cohort Studies; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Hospitals, University; Humans; Japan; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Treatment Outcome

A lethal peritonitis model was induced in mice with a Klebsiella pneumoniae isolate producing the carbapenemase OXA-48. Administration of a single dose (up to 100 mg/kg) of the antibiotic piperacillin-tazobactam, imipenem-cilastatin, ertapenem, or cefotaxime had little or no impact on lethality. Ceftazidime had the highest efficacy in vivo, which mirrored its in vitro activity; this was not the case for carbapenems. Therefore, ceftazidime may be recommended for the treatment of infections due to OXA-48 producers if they do not coproduce an extended-spectrum β-lactamase or a plasmid-mediated AmpC cephalosporinase.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Cefotaxime; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Ertapenem; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lethal Dose 50; Mice; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmids; Survival Rate

Extended-spectrum β-lactamase (ESBL)-producing bacteria coexpressing AmpC type β-lactamase (ACBL) are associated with the laboratory issue of false susceptibility to third-generation cephalosporins. This study was to evaluate laboratory tests and clinical significance of bacteremic isolates of Escherichia coli and Klebsiella pneumoniae with both ESBL and ACBL [dual-type lactamases (DTL)].. From 2006 to 2009, 78 E coli and 12 pneumoniae bacteremic isolates with reduced susceptibility to cefotaxime (CTX) or ceftazidime (CAZ) were identified and relevant patients' data were collected for analysis. Phenotypic and genotypic characterizations of these selected isolates were determined by inhibitor-based assays and polymerase chain reaction-based genetic analyses, respectively.. Among the 90 isolates, 47 had DTL production. There was an increasing annual prevalence from 29% in 2006 to 56% in 2009 (p=0.02). Phenotypic assays had a sensitivity and specificity of 57% (43/76) and 93% (13/14) for ESBL detection and 95% (58/61) and 34% (10/29) for ACBL, respectively. Among the DTL-producing isolates, phenotypic assays yielded a higher false negative rate of ESBL detection than that of ACBL detection (70% versus 6%), while all false negative ESBL results were associated with ESBL genes other than bla(CTx-M). The majority of the DTL-producing isolates were in the category of resistance to CTX (47/47, 100%) and CAZ (44/47, 94%) by the Clinical and Laboratory Standards Institute (CLSI) 2010 interpretive criteria, of which many were considered intermediate or fully susceptible to CTX (25/47, 53%) and CAZ (15/47, 32%) by the previous ones (CLSI-2009). The DTL-producing isolates exhibited a lower susceptibility rate to fluoroquinolones, aztreonam, and β-lactam/lactamase inhibitors than those with either ESBL or ACBL alone. The use of indwelling catheters or nasogastric tubes was associated with bacteremia due to the DTL isolates, but the mortality rates were not different among those due to isolates with ESBL, ACBL, or both. By multivariate analysis, Pittsburg bacteremia score and Charlson comorbidity index were the significant predictors for all-cause mortalities.. Bacteremic episodes due to DTL-producing E coli and K pneumoniae became increasingly prevalent and were often associated with coresistance to antibiotics other than β-lactams, but they were not associated with a worse prognosis than those due to ESBL- or ACBL-producing bacteria.

Topics: Aged; Analysis of Variance; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftazidime; Chi-Square Distribution; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; False Negative Reactions; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Phenotype; Prevalence; Risk Factors; Sensitivity and Specificity

Nosocomial outbreaks of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae are an increasing concern in neonatal intensive care units (NICUs). We describe an outbreak of ESBL-producing K. pneumoniae that lasted 5 months and affected 23 neonates in our NICU. Proton pump inhibitor and extended-spectrum cephalosporin exposure were significantly associated with the risk of ESBL-producing K. pneumoniae colonisation and/or infection. Thirty isolates recovered from clinical, screening and environmental samples in the NICU were studied by means of Raman spectroscopy, pulsed-field gel electrophoresis and repetitive extragenic palindromic polymerase chain reaction (rep-PCR). The Raman clustering was in good agreement with the results of the other two molecular methods. Fourteen isolates belonged to the Raman clone 1 and 16 to the Raman clone 3. Molecular analysis showed that all the strains expressed SHV-1 chromosomal resistance, plasmid-encoded TEM-1 and CTX-M-15 β-lactamases. Incompatibility groups of plasmid content identified by PCR-based replicon typing indicated that resistance dissemination was due to the clonal spread of K. pneumoniae and horizontal CTX-M-15 gene transfer between the two clones.

Topics: Amoxicillin-Potassium Clavulanate Combination; Bacterial Typing Techniques; beta-Lactamases; Cefotaxime; Disease Outbreaks; Disease Transmission, Infectious; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Fomites; France; Genes, Bacterial; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction; Risk Factors; Spectrum Analysis, Raman

In 2007, the Robert Koch Institute established the infrastructure for the national Antimicrobial Resistance Surveillance (ARS) system. Laboratories submit data of routine susceptibility testing of clinical samples from hospitals as well as from outpatient care settings in a standardized format to the Robert Koch Institute for central processing. The database for the period 2008-2011 comprises data of about 1.3 million samples from patients in hospital care and almost 800,000 samples from outpatients. Based on SIR interpretations of susceptibility, the trends of methicillin resistance of Staphylococcus aureus (MRSA) and cefotaxime non-susceptibility as an indicator of extended-spectrum beta-lactamases (ESBL) of Escherichia coli and Klebsiella pneumoniae were analyzed for four care settings or categories: hospital care, outpatient care, intensive care units, and isolates from blood cultures. After constant high levels of above 20%, the proportion of MRSA isolates showed a decline for the first time from 2010 to 2011 in hospital care overall, in intensive care units as well as in blood cultures; in outpatient care, MRSA proportions of about 13% were observed. Within the observed period, non-susceptibility to cefotaxime as an indicator of ESBL in E. coli showed an increasing trend in hospital care at a level above 10% in intensive care units, while cefotaxime non-susceptibility in K. pneumoniae was more frequent but without any trend. In outpatient care, the proportions of cefotaxime non-susceptibility increased year by year in both species resulting in nearly a doubling to 6%.

Topics: Bacteremia; beta-Lactamases; Cefotaxime; Community-Acquired Infections; Cross Infection; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Germany; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Sentinel Surveillance; Staphylococcal Infections

We evaluated the efficacy of NXL104, a novel β-lactamase inhibitor, in combination with ceftazidime (CAZ) in two murine infection models (septicemia and thigh infection). We chose two KPC-producing Klebsiella pneumoniae strains (VA-361 and VA-406) showing MICs of CAZ of ≥256 μg/ml. Septicemia was induced by the intraperitoneal injection of KPC-producing K. pneumoniae followed 30 min later by a single subcutaneous treatment with CAZ alone or CAZ-NXL104 in ratios of 2:1, 4:1, 8:1, and 16:1. In this model, the median effective doses for 50% (ED(50)) of the animals for CAZ alone versus VA-361 and VA-406 were 1,578 and 709 mg/kg of body weight, respectively. When combined with NXL104 at 2:1, 4:1, 8:1, and 16:1 ratios, the CAZ ED(50)s for VA-361 and VA-406 were reduced to 8.1 and 3.5 mg/kg, 15.1 and 3.8 mg/kg, 16.9 and 7.2 mg/kg, and 29.5 and 12.1 mg/kg, respectively. For thigh infection, neutropenia was induced by the intraperitoneal injection of cyclophosphamide at days -4 and -1 preinfection. Infection was established by the intramuscular injection of KPC-producing K. pneumoniae into the right thigh. Mice were treated 1.5 h postinfection with either CAZ alone or CAZ-NXL104 at constant ratios of 4:1. When thighs were removed at 24 h postinfection, a >2-log CFU reduction was observed for mice treated with CAZ-NXL104 at doses of ≥128:32 mg/kg. In contrast, CAZ doses of ≥1,024 mg/kg were unable to reduce the numbers of CFU. Despite resistance to CAZ and possessing a complex β-lactamase background, NXL104 combined with CAZ proved to be very effective in murine models of infection due to contemporary highly resistant KPC-producing K. pneumoniae isolates.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Disease Models, Animal; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Sepsis

The aim of this prospective study was to assess the extent of dissemination of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae at the hospital level in the United Arab Emirates (UAE).. A total of 662 Escherichia coli and Klebsiellapneumoniae samples were collected from three UAE hospitals between January and December 2008. ESBL screening and confirmatory test for ESBL phenotype were conducted using the VITEK system. Molecular typing was performed using specific primers and then sequencing.. A total of 240 (36%) samples were identified as ESBL producers, including both E. coli (n = 150) and K. pneumoniae (n = 90). All of these isolates were resistant to cefazoline and cefotaxime, but remained susceptible to imipenem. Molecular analysis revealed that, of the 240 ESBL producers, 228 carried the ESBL bla genes. A majority of the strains 199 (87%) expressed the CTX-M-15 gene. The SHV-28 gene was detected in 29 (13%) of the strains.. The present study highlighted the emergence and dissemination of CTX-M-15-producing E. coli and K. pneumoniae in the UAE. This is the first report of SHV-28-producing Enterobacteriaceae in the country.

Topics: Adolescent; Adult; Anti-Bacterial Agents; beta-Lactamases; Cefazolin; Cefotaxime; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Prospective Studies; United Arab Emirates; Young Adult

We attempt to describe the epidemiology and outcome associated with cefotaxime-resistant (CTX-R) Klebsiella spp bacteraemia. Klebsiella spp bloodstream infection episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2008 in a single institution were analysed. A total of 910 monomicrobial episodes of Klebsiella spp bacteraemia were identified during the study period. The most important sources were from urinary tract infection, unknown sources, billiary focus and catheter related infection. There were 112 (12%) CTX-R isolates. Out of 112 isolates, 98 were CTX-R by Extended-Spectrum β-Lactamase production. Shock on presentation and mortality were significantly more frequent in CTX-R than in CTX susceptible isolates. Inappropriate empirical therapy was received in 50 (45%) cases in the CTX-R Klebsiella spp group (13 cases of death, 26%). Predictive factors associated with CTX-R Klebsiella spp isolate were: previous β-lactam therapy (OR = 4.16), nosocomial acquired bacteraemia (OR = 1.93), solid organ trasplantation (OR = 2.09) and shock (OR = 1.90). Independent risk factors associated with mortality in Klebsiella spp bacteraemia were: age (OR = 1.03), liver cirrhosis (OR = 2.63), ultimately or rapidly fatal prognosis of underlying disease (OR = 2.44), shock (OR = 8.60), pneumonia (OR = 4.96) or intraabdominal (OR = 3.85) source of bacteraemia and CTX-R isolate (OR = 4.63). Klebsiella spp is an important cause of bloodstream infection. CTX-R isolates have been increasing since 2000. CTX-R is an independent factor associated with mortality in Klebsiella spp bacteraemia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefotaxime; Female; Humans; Klebsiella; Klebsiella Infections; Male; Middle Aged; Prospective Studies; Risk Factors; Treatment Outcome

The TEM-107 extended-spectrum β-lactamase detected in a Klebsiella pneumoniae clinical isolate had a Gly238Ser substitution compared to the TEM-43 β-lactamase. The MIC of ceftazidime was higher (64 μg/ml) than that of cefotaxime (2 μg/ml) for the isolate. Clavulanic acid reduced the MIC of ceftazidime 64-fold.

Topics: Adolescent; Amino Acid Substitution; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Clavulanic Acid; Conjugation, Genetic; Escherichia coli; Female; Humans; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Republic of Korea

In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Population Surveillance; Republic of Korea

Respiratory infections caused by Klebsiella pneumoniae are characterized by high rates of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. In the present study, we investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor, both derived from the virulent strain 52145R. We demonstrated that the AcrB knockout was more susceptible, not only to quinolones, but also to other antimicrobial agents, including beta-lactams, than the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model, in contrast to the wild-type strain. The results of this study suggest that, in addition to contributing to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for K. pneumoniae to resist innate immune defense mechanisms of the lung, thus facilitating the onset of pneumonia.

Topics: Animals; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Culture Media; Defensins; DNA, Bacterial; Drug Resistance, Bacterial; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Phenotype; Plasmids; Polymyxin B; Polysaccharides; Repressor Proteins; RNA, Bacterial

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Enzyme Inhibitors; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Aged; beta-Lactamases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Renal Dialysis; Republic of Korea

From 2002 to 2008, there was a significant increase in extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli isolates in European intra-abdominal infections, from 4.3% in 2002 to 11.8% in 2008 (P < 0.001), but not for ESBL-positive Klebsiella pneumoniae isolates (16.4% to 17.9% [P > 0.05]). Hospital-associated isolates were more common than community-associated isolates, at 14.0% versus 6.5%, respectively, for E. coli (P < 0.001) and 20.9% versus 5.3%, respectively, for K. pneumoniae (P < 0.01). Carbapenems were consistently the most active drugs tested.

Topics: Abdomen; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae

The aim of this research is to evaluate the recent changes in microorganisms causing spontaneous bacterial peritonitis in cirrhotic patients, antibiotic resistance, and response to empirical cephalosporin therapy. A total of 218 patients with ascites secondary to cirrhosis were enrolled. Parenteral cefotaxime or cefepime was given to patients who had a neutrophil count of 250/mm(3) or more or a positive bacterial culture of ascitic fluid. Antibiotic failure was defined by an absence of clinical improvement and an insufficient decrease in neutrophil count of ascites (<25% of initial value) by the third day of therapy. Of all the patients, 44.6% had culture-negative neutrocytic ascites, 24.8% had spontaneous bacterial peritonitis, and 10.1% had monomicrobial nonneutrocytic bacterascites. Growth in culture was observed in 76 patients (34.9%). The two most common isolated bacteria were Escherichia coli (33.8%) and coagulase-negative Staphylococcus (CoNS; 19.7%). The two cephalosporins were effective against E. coli (82%) and but not against CoNS (44%), while levofloxacin showed reasonable activity against both E. coli (71%) and CoNS (90%) in vitro. We confirmed a recent increased incidence of spontaneous bacterial peritonitis caused by Gram-positive bacteria. Levofloxacin seems to be a good alternative treatment for patients with uncomplicated spontaneous ascites infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Bacterial Infections; Cefepime; Cefotaxime; Cephalosporins; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Levofloxacin; Liver Cirrhosis; Male; Microbial Sensitivity Tests; Middle Aged; Neutrophils; Ofloxacin; Peritonitis; Pneumococcal Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections

Within the last decade, human infections caused by enterobacteria which produce the Klebsiella pneumoniae carbapenemase (KPC) became a serious therapeutic and epidemiological problem worldwide. The KPC producing strains of K. pneumoniae broadly disseminated in the USA then spread to Europe. Recently, the KPC-2 was found in Poland. In the presented study we tested 11 ertapenem resistant isolates of K. pneumoniae. The isolates were obtained from 10 patients of a regular hospital (RH) and from one patient of a palliative care hospital (PH) in Warsaw, Poland. Expression of the KPC was confirmed in all the tested isolates by the positive result of phenotypic test with boronic acid. All the isolates were also shown to harbour the bla(KPC) gene by PCR with primers targeting the core 372 bp fragment of the gene, and all but two were resistant to imipenem and meropenem as determined by the disc-diffusion method. The DNA sequence analysis of the complete bla(KPC) gene from representative isolate DM0269 revealed variant 2 of KPC (KPC-2). Tested isolates were subjected to genotyping by the PFGE with XbaI. Dendrogram based on the PFGE profiles was composed of two main branches with 82,3% of similarity. Branch A encompassed 9 isolates (93,2%), including the one from the PH-patient, while the two remaining isolates (86,5%) were located in branch B. Five isolates of the branch A were indistinguishable by the PFGE. The high genetic similarity of the branch A isolates strongly suggests the intra-hospital dissemination of epidemic K. pneumoniae KPC+ sensu stricto strain. Most probably, the strain was also transferred to the palliative care hospital. In contrast, the branch B isolates appear to belong to the distinct sensu stricto strain, that has acquired the bla(KPC) gene via horizontal transfer. This is the first report on the intra-hospital dissemination of the KPC producing K. pneumoniae in Poland. It is noteworthy, all the tested strains were also resistant to cefotaxime, ceftazidime, aztreonam, ciprofloxacin and sulphonamides, but sensitive to colistin.

Topics: Adult; Aged; Aztreonam; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftazidime; Ciprofloxacin; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Poland; Species Specificity

Extended spectrum beta-lactamases (ESBLs) are cephalosporinases that confer resistance to a wide variety of oxyimino cephalosporins and create serious therapeutic problems. In addition, the quinolone resistance qnr genes are becoming increasingly prevalent in clinical isolates, some of which also produce ESBL. This study was designed to evaluate the occurrence and genotypic distribution of ESBL producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) as well as the prevalence and distribution of qnr genes in ESBL-producing isolates in a tertiary care hospital in Korea.. We tested a total of 111 ESBL-producing isolates of E. coli and K. pneumoniae, which were collected at Kyung Hee Medical Center from November 2006 to June 2008. ESBL production was determined by the Clinical and Laboratory Standards Institute (CLSI) ESBL confirmatory test. The cefotaxime and ceftazidime resistance of the ESBL-producers were transferred to azide-resistant E. coli J53 by conjugation. The presence and identity of ESBL and qnr genes were determined by polymerase chain reaction (PCR) and nucleotide sequencing.. The prevalence of ESBLs was 17.7% (297/1,680) of E. coli and 26.5% (240/904) of K. pneumoniae in our hospital during the study periods. Of the 111 collected isolates, 69 isolates were E. coli and 42 isolates were K. pneumoniae. The most prevalent ESBL genotype was CTX-M15. Among the ESBL-producing isolates, 4 E. coli (5.8%) and 17 K. pneumoniae (40.5%) contained qnr genes. qnrB4 was the most frequent type in both E. coli and K. pneumoniae.. CTX-M15 was the most frequently encountered ESBL. In addition, a high prevalence of qnr genes among ESBL-producing K. pneumoniae was identified in this study.

Topics: Azides; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftazidime; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Korea; Microbial Sensitivity Tests; Polymerase Chain Reaction

Patients infected with bacteria producing extendedspectrum beta-lactamases (ESBL) are at higher risk of mortality and morbidity. Several mutations in genes encoding SHV, tem and CTX-M beta-lactamases have been associated with ESBL activity. This paper describes a new SHV mutation in ESBL-producing strains of Klebsiella pneumoniae isolated in Kuwait. The study included 13 K. penumoniae strains isolated from patients admitted to the Amiri hospital of Kuwait. The production of ESBL in all strains was confirmed by Vitek system and E-test. All the ESBL genes were amplified by PCR and examined by DNA sequencing. All these ESBL-positive isolates were resistant to ceftazidime and cefotaxime. DNA sequencing revealed an A815G point mutation in the bla (SHV )gene causing an asparagine (AAT) to aspartic acid (GAT) mutation at position 253 of the enzyme. This new mutation was assigned the unique number SHV-112, and the Genebank accession number EU477409. This study reports a new mutation in the SHV gene in K. pneumoniae with ESBL capability. There could be other mutations still to be found in ESBL genes of K. pneumoniae in Kuwait and probably in other middle eastern countries, and researchers in the region should make use of molecular techniques to look for more novel mutations in ESBL-producing strains of K. pneumoniae.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Base Sequence; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Conjugation, Genetic; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Kuwait; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Polymorphism, Single Nucleotide; Retrospective Studies

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Sequence Data; Poland

A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; beta-Lactamases; Carboxylic Ester Hydrolases; Cefotaxime; Cefuroxime; Cephalosporins; Cephalothin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; India; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillins; Sequence Analysis, DNA; Sequence Homology, Amino Acid

A cefotaxime-resistant Klebsiella pneumoniae ML4313 was obtained from a patient from intensive care unit of Military hospital in Tunisia. This strain was resistant to beta-lactams, aminoglycosides, quinolones and phenicols, and tetracyclines. It was identified as producer of extended-spectrum beta-lactamases (ESBL) by double-disk synergy test between amoxicillin-clavulanate and cefotaxime, ceftriaxone, ceftazidime and aztreonam. The ESBL was identified as CTX-M-28 by sequencing of PCR products and by isoelectric focusing. The ESBL resistance was transferred by a 50kb plasmid. CTX-M-28 is closely related to CTX-M-15. This is the first description of this enzyme in Tunisia.

Topics: Amino Acid Sequence; Amino Acid Substitution; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Hospitals, Military; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Mutation, Missense; R Factors; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Tunisia

Multiresistant, extended spectrum beta lactamase (ESBL)-producing pathogens are an increasing problem in daily clinical life. This paper summarizes the development of resistance as well as epidemiology, diagnostics, and treatment of ESBL-producing micro-organisms. We analyzed microbiological data collected at the Grosshadern Clinic in Germany between 1996 and 2007, in order to assess the importance of these micro-organisms to medical practice and surgical care units.. Pathogens were isolated from 28,894 patients with Escherichia coli and 10,903 with Klebsiella pneumoniae pathogens between 1996 and 2006 and tested for ESBL production. For the year 2007 we have analyzed the complete spectrum of ESBL-producing pathogens and their distribution to different departments of the clinic. The agar diffusion test with five cephalosporins and an automated detection system (BD Phoenix) were used for screening purposes. Positive results were verified with the E- and double-disc agar diffusion tests.. The most important pathogens isolated from patients were E. coli and K. pneumoniae. Analysis of ESBL-producing E. coli pathogens from 1996 to 2006 showed the prevalence increasing from 0% to 4.1%. For ESBL-producing K. pneumoniae, we also found a prevalence rising from 0.3% in 1996 to 6.6% in 2006. For the year 2007 a further increase in ESBL-producing pathogens was detected, reaching 182 cases, with 118 of ESBL-producing E. coli (5.7 %) and 39 of ESBL-producing K. pneumoniae (7.4%). Of these, 24 cases with E. coli and nine with K. pneumoniae were surgery patients (20% and 23%, respectively).. The results show an increasing prevalence of ESBL-producing pathogens in hospitalized patients and in surgical departments. The resulting rise in treatment costs and patient risk require thorough knowledge of risk factors, therapy, and preventive measures.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Cefotaxime; Ceftriaxone; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Europe; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Risk Factors; Surgical Wound Infection

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Cambodia; Cefotaxime; Child; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; HIV Infections; Humans; Klebsiella; Klebsiella Infections; Opportunistic Infections

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Female; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids

Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the beta-lactamase bla KPC-2 gene was located on a novel Tn3-based transposon, Tn4401. Tn4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the beta-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, ISKpn6 and ISKpn7. Tn4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn4401a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn4401b, which was found in the Colombian isolates. In all isolates tested, Tn4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn4401 is likely at the origin of carbapenem-hydrolyzing beta-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.

Topics: Base Sequence; beta-Lactamases; beta-Lactams; Cloning, Molecular; Colombia; DNA Transposable Elements; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA; United States

An outbreak of cephalosporin-resistant Klebsiella pneumoniae occurred in a neonatal intensive care unit in São Paulo, Brazil. Of the 10 pulsotypes identified during the outbreak and follow-up periods, nine produced CTX-M-2 or its new variant CTX-M-59 and one produced SHV-5. bla(CTX-M-2/59) genes were located on closely related plasmids that were transferable.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Cephalosporins; Disease Outbreaks; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Polymerase Chain Reaction

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae have rapidly spread worldwide and pose a serious threat for health care-associated (HA) infection. We conducted molecular detection and characterization of ESBL-related bla genes, including bla(TEM), bla(SHV), bla(CTX-M), bla(VEB), bla(OXA), bla(PER), and bla(GES), among 362 isolates of ESBL-producing E. coli (n = 235) and ESBL-producing K. pneumoniae (n = 127) collected from patients who met the definition of HA infection at two major university hospitals in Thailand from December 2004 to May 2005. The prevalence of ESBL-producing E. coli and ESBL-producing K. pneumoniae, patient demographics and the susceptibilities of these bacteria to various antimicrobial agents were described. A total of 87.3% of isolates carried several bla genes. The prevalence of bla(CTX-M) was strikingly high: 99.6% for ESBL-producing E. coli (CTX-M-14, -15, -27, -40, and -55) and 99.2% for ESBL-producing K. pneumoniae (CTX-M-3, -14, -15, -27, and -55). ISEcp1 was found in the upstream region of bla(CTX-M) in most isolates. Up to 77.0% and 71.7% of ESBL-producing E. coli and ESBL-producing K. pneumoniae, respectively, carried bla(TEM); all of them encoded TEM-1. ESBL-producing K. pneumoniae carried bla(SHV) at 87.4% (SHV-1, -2a, -11, -12, -27, -71, and -75) but only at 3.8% for ESBL-producing E. coli (SHV-11 and -12). bla genes encoding VEB-1 and OXA-10 were found in both ESBL-producing E. coli (8.5% and 8.1%, respectively) and ESBL-producing K. pneumoniae (10.2% and 11.8%, respectively). None of the isolates were positive for bla(PER) and bla(GES). Pulsed-field gel electrophoresis analysis demonstrated that there was no major clonal relationship among these ESBL producers. This is the first study to report CTX-M-3, CTX-M-27, CTX-M-40, SHV-27, SHV-71, and SHV-75 in Thailand and to show that CTX-M ESBL is highly endemic in the country.

Topics: Adult; Bacterial Proteins; beta-Lactamases; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Endemic Diseases; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymerase Chain Reaction; Sequence Analysis, DNA; Thailand

The first outbreak of carbapenem-resistant Klebsiella pneumoniae isolates producing the plasmid-encoded carbapenem-hydrolyzing oxacillinase OXA-48 is reported. The 39 isolates belonged to two different clones and were collected at the University Hospital of Istanbul, Turkey, from May 2006 to February 2007, and they coproduced various beta-lactamases (SHV-12, OXA-9, and TEM-1 for clone A and CTX-M-15, TEM-1, and OXA-1 for clone B).

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Models, Genetic; Turkey

Topics: Adult; Anti-Bacterial Agents; Belgium; beta-Lactamases; beta-Lactams; Carbapenems; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Plasmids

A clinical strain of Klebsiella pneumoniae was found to possess the chromosomal gene bla(SHV-56), encoding a new inhibitor-resistant beta-lactamase with a pI of 7.6. SHV-56 is derived from SHV-11 by the single substitution K234R. This mutation therefore evidences a new critical site for inhibitor resistance among SHV enzymes.

Topics: Aged; Amino Acid Substitution; Base Sequence; beta-Lactam Resistance; beta-Lactamases; DNA Primers; DNA, Bacterial; Female; Genes, Bacterial; Humans; Isoelectric Point; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Mutagenesis, Insertional; Recombinant Proteins

beta-Lactamases produced by urine isolates from patients in long-term care facilities (LTCFs), outpatient, clinics, and one hospital in a U.S. community were characterized. A total of 1.3% of all Escherichia coli and Klebsiella pneumoniae isolates collected from patients in 30 LTCFs and various outpatient clinics produced extended-spectrum beta-lactamases (ESBLs) and/or imported AmpC beta-lactamases.

Topics: Bacterial Proteins; beta-Lactamases; Community-Acquired Infections; Disease Reservoirs; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Population Surveillance; United States

Characterisation of extended-spectrum beta-lactamase (ESBL) genes and their genetic environments as well as the presence of integrons were analysed in nine Klebsiella pneumoniae and two Escherichia coli ESBL-positive isolates recovered in the Centre of Bone Marrow Transplantation of Tunisia. All strains harboured the bla(CTX-M-15) gene and presented minimum inhibitory concentrations for cefotaxime and ceftazidime of 256-1024 mg L(-1) and 16-512 mg L(-1), respectively, and eight of them showed different pulsed-field gel electrophoresis patterns. The bla(OXA-1) and bla(TEM-1) genes were detected in eight and ten strains, respectively. In addition, bla(SHV-1), bla(SHV-11) and bla(SHV-27) were found in six, one and one K. pneumoniae strains, respectively. The new variant bla(SHV-103) was characterised in one K. pneumoniae strain. The intI1 gene was detected in eight K. pneumoniae strains and the dfrA5+ereA2 and aadA gene cassettes were found in one and five strains, respectively. All strains harboured a 70 kb plasmid, and its transference in addition to bla(CTX-M-15), bla(TEM-1b) and bla(OXA-1) genes was demonstrated from three K. pneumoniae to E. coli. ISEcp1 and orf477 were located upstream and downstream, respectively, of the bla(CTX-M-15) gene in 10 strains. The occurrence of the bla(CTX-M-15) gene in unrelated strains might have originated from the dissemination of mobile genetic elements in which ISEcp1 may have played an important role.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Escherichia coli; Escherichia coli Infections; Hospitalization; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Stem Cell Transplantation; Tunisia

Topics: Aged, 80 and over; Anti-Bacterial Agents; Cefotaxime; Female; Humans; Hyperammonemia; Injections, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Neurotoxicity Syndromes; Proteus Infections; Proteus mirabilis; Treatment Outcome; Urinary Bladder Calculi; Urinary Retention; Urinary Tract Infections

Clinical isolates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum beta-lactamases or plasmid-mediated AmpC beta-lactamases were screened for qnrA and qnrB genes. QnrB was present in 54 of 54 DHA-1-producing K. pneumoniae isolates and 10 of 45 SHV-12-producing ones, suggesting that the distribution of plasmids conferring resistance to extended-spectrum cephalosporins and quinolones in clinical isolates of K. pneumoniae is widespread.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Quinolones

A Klebsiella pneumoniae strain resistant to third-generation cephalosporins was isolated in the eastern Netherlands. The strain was found to carry a novel extended-spectrum beta-lactamase, namely, SHV-31. The combination of the two mutations by which SHV-31 differs from SHV-1, namely, L35Q and E240K, had previously only been described in association with one or more additional mutations.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Netherlands; Plasmids

Antibiotic resistance continues to reduce the number of available antibiotics, increasing the need for novel antibacterial drugs. Since the seminal work of Sir Alexander Fleming, antibiotic identification has been based exclusively on the inhibition of bacterial growth in vitro. Recently, inhibitors of bacterial virulence which interfere with bacterial pathogenesis mechanisms have been proposed as an alternative to antibiotics, and a few were discovered using assays targeting specific virulence mechanisms. Here we designed a simple surrogate host model for the measurement of virulence and systematic discovery of anti-virulence molecules, based on the interaction of Tetrahymena pyriformis and Klebsiella pneumoniae cells. We screened a library of small molecules and identified several inhibitors of virulence. In a mouse pneumonia model we confirmed that an anti-virulence molecule displayed antibacterial activity against Klebsiella pneumoniae and Pseudomonas aeruginosa, by reducing dramatically the bacterial load in the lungs. This molecule did not inhibit bacterial growth in vitro but prevented biosynthesis of the Klebsiella capsule and lipopolysaccharides, a key requirement for virulence. Our results demonstrate that anti-virulence molecules represent an alternative to antibiotics and those can be discovered using non-animal host models.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Cefotaxime; Cefpodoxime; Ceftizoxime; Cyclophosphamide; Disease Models, Animal; Female; Klebsiella Infections; Klebsiella pneumoniae; Lung; Mice; Mice, Inbred BALB C; Molecular Structure; Mutation; Neutropenia; Pseudomonas aeruginosa; Tetrahymena pyriformis; Time Factors; Triazines; Virulence

Klebsiella pneumoniae has long been a prominent cause of nosocomial infections and outbreaks have been observed in the intensive care units and in high risk groups. We present here a brief report on an outbreak of Klebsiella pneumoniae which occurred in a neonatal intensive care unit in our teaching hospital. As neonates are at highest risk for acquisition of Klebsiella pneumoniae producing extended spectrum beta-lactamase, infection control policies and procedures should be strictly followed to prevent such outbreaks.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporin Resistance; Cross Infection; Disease Outbreaks; Hospitals, Teaching; Humans; India; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae

There are numerous types of extended spectrum beta-lactamases (ESBLs), of which TEM and SHV are predominant among Klebsiella pneumoniae strains. Nosocomial infections with strains of K. pneumoniae are common in healthcare centers in Iran. However, no information is available on the prevalence of different phenotypes of ESBL strains in Tehran hospitals.. To determine the resistance of K. pneumoniae to beta-lactam antibiotics in Tehran hospitals, 145 isolates were tested using the disk diffusion method. The MICs for ceftazidime were also determined using microbroth dilution assay. Isolates showing MIC >/=4 for ceftazidime were subjected to PCR to target the bla(SHV) and bla(TEM) genes and screened for ESBL production by the phenotypic confirmatory method.. All strains were susceptible to imipenem. Resistance to ceftazidime and cefotaxime were 31% and 32%, respectively. Fifty-six isolates showed MIC >/=4 microg/ml for ceftazidime, of which 50 were positive for ESBL in the phenotypic confirmatory test. The prevalence of bla(SHV) and bla(TEM) among these isolates was 69.6% (n=39) and 32.1% (n=18), respectively. Resistance to ciprofloxacin was found among 32% of the ESBL strains.. SHV is the dominant enzyme among the ESBL-producing strains of Klebsiella pneumoniae in Iran. The high rate of co-resistance to ceftazidime and ciprofloxacin is a matter of concern and treatment requires further attention to the results of susceptibility.

Topics: Base Sequence; beta-Lactamases; Cefotaxime; Ceftazidime; Cross Infection; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Iran; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymerase Chain Reaction

The aim of this study was to determine the prevalence of extended-spectrum beta-lactamases (ESBLs) in nosocomial bacteremia isolates of Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca at Hacettepe University Adult Hospital in Ankara, Turkey. A total of 344 blood culture isolates of E. coli (n=244), K. pneumoniae (n=86) and K. oxytoca (n=34) were included in the study from January 2003 to November 2005. Only one isolate from one patient was tested in the study. The isolates with ceftazidime and/or cefotaxime MIC values > or =1 microg/ml were tested by ceftazidime-ceftazidime/clavulanic acid and cefotaxime-cefotaxime/clavulanic acid Etest (AB Biodisk Solna, Sweden) strips and evaluated as ESBL positive if the ratio was > or =8. Of the isolates, 33% (74/224) of E. coli, 31.4% (27/86) of K. pneumoniae and 47% (16/34) of K. oxytoca were detected as ESBL producers by any kind of two strips. However, 5.4% (4/74) of E. coli, 3.7% (1/27) of K. pneumoniae and 43.1% (7/16) of K. oxytoca ESBL-producing isolates could be detected only by cefotaxime-cefotaxime/clavulanic acid strips. It is important to use cefotaxime-cefotaxime/clavulanic acid as well as ceftazidime-ceftazidime/clavulanic acid ratio for detection of ESBL types that preferentially hydrolyze cefotaxime. Since prevalence of ESBL production is high in nosocomial E. coli and Klebsiella spp. isolates in our hospital, surveillance of antibiotic susceptibility patterns is important for the empirical treatment of bacteremic patients.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefotaxime; Ceftazidime; Clavulanic Acid; Cross Infection; Drug Combinations; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Microbial Sensitivity Tests; Prevalence; Turkey

During a survey of the prevalent subtypes of extended-spectrum beta -lactamases in a university hospital in Korea, a nosocomial outbreak of Escherichia coli producing CTX-M-15 and OXA-30 beta -lactamases was detected. The outbreak comprised various infections, including bloodstream infections and colonization, and persisted for several months in various areas of the hospital.

Topics: beta-Lactamases; Cefotaxime; Ceftazidime; Cross Infection; Disease Outbreaks; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Korea; Prevalence

A search of the computerized database at the National Taiwan University Hospital was made for cefotaxime-resistant and cefmetazole-susceptible isolates of Escherichia coli and Klebsiella pneumoniae (which may be extended-spectrum beta-lactamase-producing strains) in pediatric wards and intensive care units between 1999 and 2001. Fourteen infectious episodes attributed only to study bacteria were identified, including 7 episodes of bacteremia. Nine patients (64.3%) had underlying medical conditions: 3 were premature babies, 3 were immunodeficient, 2 had malignancy, and 2 had a congenital heart disease with active heart failure even after surgery. Among the 7 patients with bacteremias, 5 may be catheter-related; 6 were treated with carbapenems and 1 was treated with cefmetazole successfully, with or without the removal of the catheter. Before the acquisition of the infection, a history of stay in an intensive care unit within 4 weeks was noted in 10 cases (71.4%); a history of use of extended-spectrum cephalosporins within 4 weeks was also noted in 6 cases (42.9%). Cefmetazole, with or without an aminoglycoside, was clinically effective in 6 cases (42.8%). Except for 1 episode of pneumonia that ended in mortality, all of the infectious episodes were successfully treated. The mortality rate was 7.1%.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Carbapenems; Catheterization; Cefmetazole; Cefotaxime; Child; Child, Preschool; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Heart Defects, Congenital; Humans; Immunologic Deficiency Syndromes; Infant; Inpatients; Klebsiella Infections; Klebsiella pneumoniae; Male; Neoplasms; Premature Birth; Taiwan

During a survey of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Bulgaria in 2001-2002, three isolates from Sofia (two Escherichia coli, one Klebsiella pneumoniae) showed cefotaxime MICs that were decreased in the presence of clavulanate and were 2-8-fold higher than those of ceftazidime. Resistance was transferred to a sensitive recipient strain of E. coli. Both wild-type and transconjugant strains produced a cefotaxime-hydrolysing beta-lactamase of pI 8.8. Sequencing of the PCR product obtained with oligonucleotide primers binding outside the coding region identified this beta-lactamase as CTX-M-15. To our knowledge, this is the first report of CTX-M-15 in Bulgaria.

Topics: Anti-Bacterial Agents; beta-Lactamases; Bulgaria; Cefotaxime; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction

Topics: Anti-Bacterial Agents; Cataract; Cefotaxime; Endophthalmitis; Eye Infections, Bacterial; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Klebsiella Infections; Klebsiella pneumoniae; Ultrasonography

We compared trends of annual resistance rates calculated from results for all isolates and for the first isolate of Staphylococcus aureus, Klebsiella pneumoniae, and Acinetobacter baumannii per patient over a 3-year period from 2001 through 2003. Antimicrobial susceptibility results of inpatients were extracted from a computerized database. Annual resistance rates of a species were calculated by two methods: (i) from results for all isolates, even those from patients with multiple isolates in a given year and (ii) from results for the first isolate from a patient in a given year, regardless of susceptibility profile or specimen type. Rates of methicillin-resistant S. aureus (MRSA) did not differ among all isolates (79.9, 78.8 and 79.6%; P = 0.86), but decreased for the first isolate per patient (70.2, 65.7, and 64.1%; P = 0.006) over time. Annual duplication rates of methicillin-susceptible S. aureus (MSSA) decreased (39.6, 37.6, and 31.7%; P = 0.01), but those of MRSA increased significantly (64.3, 67.8, and 68.9%; P = 0.004). Rates of cefotaxime-resistant K. pneumoniae did not differ over time by either method, and rates of imipenem-resistant A. baumannii decreased over time by both methods. Duplication rates did not differ for either susceptible or resistant isolates of K. pneumoniae and A. baumannii. The trends in MRSA rate differed by the two methods because of the different proportion of duplicate isolates per year. MRSA rates might be increasingly overestimated for all isolates. These results suggest that the method of calculating results for the first isolate per patient may remove the effect of duplication, allowing the simple and unambiguous analysis of cumulative susceptibility rates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cefotaxime; Drug Resistance, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Time Factors

To identify the ESBL gene and the prevalence in Escherichia coli and Klebsiella pneumoniae strain isolated from Huashan Hospital, Shanghai.. Isolates were confirmed as an ESBL producing strain by double-disk synergy test and NCCLS Confirmatory Test. Antibiotic susceptibilities were determined by standard agar dilution procedure on Mueller-Hinton agar. To determine whether the resistance was transferable, the conjugation experiment was performed; plasmids were isolated from clinical isolates and transcojugants. The partial bla(gene) of ESBL producing isolates and their transcojugants were detected by PCR using universal primers for TEM, SHV, CTX-M-1group, Toho-1group, CTX-M-13group respectively. The entire bla(CTX-M-13) group were amplified by PCR using the primers outside the Open Reading Frame (ORF) of CTX-M-13group beta-lactamases; the PCR products of entire bla(CTX-M-13)group were cloned into vector and the recombinant plasmids were transformed into the recipient strain for expression; the PCR products were also directly sequenced and analyzed; the clinical isolates of ESBL producers were detected by PFGE.. ESBL producers were resistant to most beta-lactams and non-beta-lactams. Most transconjugants were obtained at frequency of 10(-4) approximately 10(-5) and resistance to non-beta-lactams was cotransferred with the ESBL activity to the transconjugant. A plasmid of about > 23.1 kb was obtained from each tansconjugant by plasmid extraction. Partial gene amplification products of CTX-M-13 group gene were obtained from isolates and their transconjugants. The bla(CTX-M-13)group from 4 transconjugants were identified as bla(CTX-M-14), and other six were bla(CTX-M-24); those ESBLs were mediated by plasmids (> 23.1 kb); the transformants producing CTX-M-14 or CTX-M-24 were resistant to most beta-lactams, which were much more resistant to cefotaxime than to ceftazidine; PFGE patterns of those isolates were different.. clinical isolate of Escherichia coli and Klebsiella pneumoniae isolated from Huashan Hospital, Shanhai produced CTX-M-14 or CTX-M-24, which caused the isolate resistant to most beta-lactams; no clone spread in those isolates was found.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae

To describe the antibiotic resistant mode of extended-spectrum beta-lactamases(ESBLs) producing Escherichia coli (E. coli.) and Klebsiella pneumoniae (KPn) in surgical intensive care unit(SICU), and to implore the molecular epidemiology of ESBLs coding genes of these strains.. The minimal inhibitory concentrations (MICs) at antibiotics were examined by agar dilution method. The ESBLs coding genes were amplified by TEM, SHV and CTX-M specific primers. Amplicons of such genes with conjugates' plasmids as templates were sequenced.. In vitro susceptibility tests of ESBLs producing strains showed a high level of resistance to most of the beta-lactam biotics, especially cefotaxime. 93.5% of these ESBLs positive strains contained CTX-M group genes,and 38.7% of the strains contained SHV genes. By sequencing, some genotype were determined: TEM-1, CTX-M-1,3,14,22.. ESBLs producing strains were resistant to most of the beta-lactam biotics. The most prevalent ESBLs genotype of ESBLs produced by E coli and KPn in SICU was CTX-M subgroup. The most probable reason might be the extensive use of cefotaxime.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Cephalosporin Resistance; China; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Endophthalmitis subsequent to Klebsiella sepsis leads to functional blindness in most cases and is very difficult to treat. Every successful therapeutic modality can therefore help in creating an optimal therapeutic plan.. A 69-year old diabetic patient exhibited bilateral Klebsiella endophthalmitis with sepsis after a pneumonia. Two intravenous antibiotics were used: aminoglycosides (Gentamycin) and cephalosporins (Cefotaxim or Cefuroxim) with local parabulbar injections of Prednisolon. The long-term follow-up of four years provided some overview of morphological aspects of the development of endophthalmitis. Characteristic greyish hypopyon was seen in both eyes, which was more pronounced in the left eye than in the right. The left eye became phthisic. After resorption of the hypopyon in the right eye and prolonged resorption of the subretinal abscess for 9 months a useful visual acuity at 0.2 was achieved. Two years after the endophthalmitis a cataract surgery with implantation of a posterior chamber silicon lens was performed and good visual acuity (0.6) was achieved. After four years, the subretinal abscess left an extremely large, sharp bordered, unpigmented scar up to the sclera.. An early diagnosis and adequate long-time antibiotic therapy under the co-operative supervision of an ophthalmologist with internist appears to be most important for the therapeutic success in Klebsiella endophthalmitis.

Topics: Abscess; Aged; Cefotaxime; Cefuroxime; Drug Therapy, Combination; Endophthalmitis; Follow-Up Studies; Gentamicins; Humans; Klebsiella Infections; Lenses, Intraocular; Long-Term Care; Male; Ophthalmoscopy; Pneumonia, Bacterial; Prednisolone; Retinal Diseases; Sepsis

The authors report a fatal case of acute bacterial myocarditis in a nonneutropenic child with acute lymphoblastic leukemia. She was admitted to the hospital with a urinary tract infection resulting from and remained persistently febrile despite resolution of the infection. On hospital day 4 signs of acute cardiac failure developed. Despite aggressive resuscitation measures, she died. Pathologic examination revealed the cause of death to be bacterial myocarditis. In addition, she was found to have a generalized decrease in her serum immunoglobulin levels. Acute bacterial myocarditis in patients with malignancy has been rarely reported. The rapid clinical deterioration and death in the patient in this report is particularly interesting.

Topics: Acute Disease; Agammaglobulinemia; Antineoplastic Combined Chemotherapy Protocols; Cefotaxime; Child; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Myocarditis; Oxacillin; Pericarditis; Pleurisy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Shoulder Pain; Tobramycin; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

In a previous investigation of the genetic characterization of extended-spectrum beta-lactamases (ESBLs) in Klebsiella pneumoniae from Zagreb, Croatia, 20 strains were found to produce SHV-2 beta-lactamase. Those strains displayed varying degrees of beta-lactam resistance and a wide range of beta-lactamase activity. We concluded that more resistant isolates were hyperproducers of SHV-2 beta-lactamase.. In this investigation, we tried to develop hyperproducing variants from 8 low-level SHV-2 beta-lactamase-producing Klebsiella strains by subculturing them in serum containing therapeutic concentrations of cefotaxime (CTX).. In most cases, there was a moderate increase in CTX resistance (twofold to threefold), except in one strain which displayed a 16-fold increase in the minimum inhibitory concentration (MIC) of CTX after incubation in the serum. That strain showed a marked increase in enzyme activity as well. The strains with a moderate increase in CTX MIC did not produce more enzyme after exposure to the serum, except for one strain which had a threefold rise in beta-lactamase activity after exposure to serum.. In this investigation, it was established that the mutants with high-level CTX resistance developed very quickly in the biological fluids containing therapeutic concentrations of CTX. It is reasonable to expect that a similar process occurs in patients infected with an ESBL-producing K. pneumoniae strain during antibiotic treatment. Since most of the high-level CTX-resistant mutants did not have a marked rise in beta-lactamase activity after exposure to serum, it is possible that the elevated resistance was due to some other mechanism, such as reduced penicillin-binding protein affinity, changes in outer membrane proteins or efflux by multidrug efflux pumps.

Topics: beta-Lactamases; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Culture Media; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutagenesis, Site-Directed; Mutation; Plasmids

The disk screening methods for extended-spectrum beta-lactamase-producing strains were evaluated. The confirmatory work is reduced significantly in settings such as those in this study, by changing the cefpodoxime breakpoint to < or =20 mm and by not testing cefoxitin-resistant isolates. Cefotaxime and ceftazidime disk screening is reliable, and the laboratory-prepared cefotaxime- and ceftazidime-clavulanic acid disks are stable at -20 degrees C for 12 weeks.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Clavulanic Acid; Drug Stability; Escherichia coli; Escherichia coli Infections; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Prevalence

Topics: Adult; Bioprosthesis; Cefotaxime; Diuretics; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis; Hepatitis C, Chronic; HIV Infections; Humans; Immunocompromised Host; Klebsiella; Klebsiella Infections; Male; Postoperative Complications; Pulmonary Valve; Staphylococcal Infections

A prospective study conducted among Jordanian ICU patients in 1997 using Etest identified resistance rates among isolates of E. coli (25%-44%), Enterobacter spp. (54%-62%), and Klebsiella spp. (30%-80%) to extended-spectrum B-lactams (ESBLs): ceftazidime, cefotaxime, ceftriaxone, and aztreonam. All these isolates were susceptible to imipenem and showed low resistance rate to ciprofloxacin (5%-19%) and amikacin (13%-18%). Higher and significant resistance rates of Klebsiella isolates to ceftazidime (80%) and aztreonam (65%) were observed in 1997 compared with a previous study performed in 1994. The majority of Klebsiella pneumoniae (70%) express different ESBL phenotypes that were almost resistant to aztreonam and ceftazidime but susceptible or resistant to cefotaxime and/or ceftriaxone. This prospective study strongly suggests that ESBL production of Klebsiella pneumoniae isolates have been highly disseminated among ICU patients during 1997.

Topics: Aztreonam; beta-Lactam Resistance; Cefotaxime; Ceftazidime; Ceftriaxone; Cross Infection; Gram-Negative Bacteria; Humans; Incidence; Intensive Care Units; Jordan; Klebsiella Infections; Klebsiella pneumoniae; Lactams; Microbial Sensitivity Tests; Prospective Studies; Sensitivity and Specificity

Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.

Topics: Amino Acid Sequence; Aztreonam; Bacterial Proteins; Base Sequence; beta-Lactamases; Cefepime; Cefotaxime; Cefoxitin; Ceftazidime; Ceftriaxone; Cephalosporins; Cephamycins; Cloning, Molecular; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; France; Hafnia; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Monobactams; Plasmids; Polymerase Chain Reaction

In 1995, changes in our hospital formulary were made to limit an outbreak of vancomycin-resistant enterococci and resulted in decreased usage of cephalosporins, imipenem, clindamycin, and vancomycin and increased usage of beta-lactam/beta-lactamase-inhibitor antibiotics. In this report, the effect of this formulary change on other resistant pathogens is described. Following the formulary change, there was a reduction in the monthly number (mean +/- SD) of patients with methicillin-resistant Staphylococcus aureus (from 21.9 +/- 8.1 to 17.2 +/- 7.2 patients/1,000 discharges; P = .03) and ceftazidime-resistant Klebsiella pneumoniae (from 8.6 +/- 4.3 to 5.7 +/- 4.0 patients/1,000 discharges; P = .02). However, there was an increase in the number of patients with cultures positive for cefotaxime-resistant Acinetobacter species (from 2.4 +/- 2.2 to 5.4 +/- 4.0 patients/1,000 discharges; P = .02). Altering an antibiotic formulary may be a possible mechanism to contain the spread of selected resistant pathogens. However, close surveillance is needed to detect the emergence of other resistant pathogens.

Topics: Acinetobacter; Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Formularies, Hospital as Topic; Humans; Klebsiella Infections; Klebsiella pneumoniae; Methicillin Resistance; Staphylococcal Infections; Staphylococcus aureus

Encapsulated Klebsiella pneumoniae strains frequently induce fatal nosocomial pneumonia. Cefodizime (CEF) as an antibiotic is suspected to enhance host resistance against various microbial invasions through interactions with bacteria and host cells. To investigate the influence of CEF on the pulmonary response to Klebsiella that does not merely result from direct bacterial clearance by the drug, we inoculated mice with heat-killed fluorescein isothiocyanate-labeled K. pneumoniae. CEF upregulated (P < 0.01) the early Klebsiella-induced secretion of tumor necrosis factor alpha, as well as the number (P < 0.01) and phagocytic efficacy (P < 0.001) of alveolar macrophages. By contrast, the late polymorphonuclear neutrophil recruitment (P < 0.05) and levels of interleukin-1 alpha (IL-1alpha) (P < 0.05) and IL-6 (P < 0.05) were reduced. The stimulation of an early immune response by CEF followed by late reduction in inflammation may be beneficial against bacterial pneumonia.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cefotaxime; Cephalosporins; Inflammation; Injections, Subcutaneous; Interleukins; Klebsiella Infections; Klebsiella pneumoniae; Lung; Macrophages, Alveolar; Mice; Neutrophils; Tumor Necrosis Factor-alpha

Pyogenic liver abscess are macroscopic collections of pus within the hepatic parenchyma after a bacterial infection. These infections are usually polymicrobial in nature, and in most occasions due to biliary tract diseases or cryptogenetic in origin. Monomicrobial hepatic abscess caused by Klebsiella pneumoniae are uncommon lesions in western countries. These lesions are associated with underlying diseases, particularly diabetes mellitus, and are frequently complicated with septic metastasis. We report here three cases of monomicrobial liver abscess caused by Klebsiella pneumoniae in diabetic patients, without septic metastasis and a favourable outcome.

Topics: Aged; Cefotaxime; Cephalosporins; Diabetes Complications; Follow-Up Studies; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Middle Aged; Time Factors; Tomography, X-Ray Computed

In this communication, we describe the occurrence of strains of Klebsiella pneumoniae resistant to cephalosporins of all generations and to aztreonam due to their production of Extended Spectrum beta-Lactamases (ESBLs), in two hospitals in Slovakia. They were found to transfer the genetic determinants of resistance of cefotaxime, ceftazidime and aztreonam and of ESBL production to suitable recipient strains of Escherichia coli K-12 No. 3110 and Proteus mirabilis P-38. Six donor K. pneumoniae strains were collected from six prematurely born babies gradually infected with strains of K. pneumoniae resistant to cefotaxime, ceftazidime and aztreonam. All six strains of K. pneumoniae gave an identical pattern in ESBL testing (double-disk diffusion test). The second cycle of transfers to nalidixin-resistant E. coli K-12 No. 185 nal+ also confirmed that all transconjugants were resistant to all beta-lactams tested. We conclude that a single gene was transferred from donor strains which confers 'en bloc' the resistance to the beta-lactams tested. Four strains of K. pneumoniae produced a uniform type of ESBI. Although with different quantitative expression. All transconjugants tested produced identical types of ESBL as did the donor strains of K. pneumoniae. This transfer of an identical pattern of ESBL production was confirmed also in the second cycle of transfers. Cefotaxime, ceftazidime and aztreonam were actively hydrolysed (as shown by the relative rate of hydrolysis [Vmax]) by strains of K. pneumoniae as well as by transconjugant colonies and clavulanate inhibited the hydrolysis of these beta-lactam antibiotics.

Topics: Aztreonam; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Conjugation, Genetic; Drug Resistance, Multiple; Escherichia coli; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Monobactams; Proteus mirabilis

The production of beta-lactamases, the outer membrane protein (OMP) patterns, some clinical impacts and the prevalence of resistance among cefuroxime-resistant Danish clinical isolates of Klebsiella pneumoniae were investigated. Fifteen resistant and five susceptible strains were collected from 14 patients during 1991-1994. Isolates from five patients produced extended-spectrum beta-lactamases (ESBLs). Cefuroxime resistance was accompanied by a 10-fold elevation of ciprofloxacin minimal inhibitory concentration (MIC), and for some isolates by an alteration of the OMP pattern. The relationship between alterations of the OMP patterns and cross-resistance to ciprofloxacin and the other antibiotics tested was not universal. Ten of the cefuroxime-resistant strains had elevated MICs of cefotaxime or ceftazidime, but the MICs were still below the breakpoint for susceptibility. The MICs of imipenem were not affected. Nosocomial infection or long-term colonization with resistant strains may be of importance since five patients were not treated with cefuroxime prior to isolation of the resistant strain, and all patients had either serious diseases or stayed at the hospital for a long period of time. The prevalence of cefuroxime and ciprofloxacin resistance among clinical isolates from Copenhagen county during 1990-1995 was 8.3% and 7.5%, respectively, but higher for urinary tract specimens. A greater consumption of cefuroxime as compared to cefotaxime and ceftazidime in this study, as seen generally in Denmark, indicated that ESBLs produced by the investigated strains of K. pneumoniae may be selected with cefuroxime.

Topics: Bacterial Outer Membrane Proteins; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Cefuroxime; Denmark; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Six Klebsiella pneumoniae strains were collected from two hospitals in Ostrava, Czech republic. Four strains (Nos. 209, 217, 218, 222) were isolated from sputa of critically ill patients from Municipal Hospital Vítkovice-Ostrava. They were resistant to cephalothin, cefotaxime, and ceftazidime (MIC > 100 mg x l-1). Strain No. 218 was intermediately resistant also to ofloxacin and aztreonam (MIC = 12.5 mg x l-1), strain No. 222 was resistant to aztreonam (MIC = 50 mg x l-1). Determinants of resistance to cephalothin, cefotaxime, aztreonam and ceftazidime were transferred to recipient strains of P. mirabilis P-38 rif+ and E. coli K-12 No. 3110 rif+ by all four strains. Synergy between clavulanate-cefotaxime, clavulanate-ceftazidime and clavulanate-aztreonam indicated production of ESBLs by these strains. Two strains, No. 214 and 224, from patients of the ICU in the University Hospital were resistant to cephalothin, cefotaxime and ceftazidime (MIC > 100 mg x l-1). Strain No. 214 was intermediately resistant to aztreonam and ofloxacin (MIC = 12.5 mg x l-1) and strain No. 224 was highly resistant to aztreonam (MIC = 50 mg x l-1). Synergy between clavulanate and cefotaxime as well as between clavulanate and aztreonam, but not between clavulanate and ceftazidime corresponds with non-transferable ceftazidime resistance in strains No. 214 and 224 and indicates different types of ESBL in strains from each of two hospitals.

Topics: Aztreonam; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalothin; Czech Republic; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Ofloxacin

Topics: Adolescent; beta-Lactamases; Cefotaxime; Cephalosporins; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Treatment Failure

The in vitro and in vivo antibacterial activities of sulopenem (CP-70,429),a new parenteral penem antibiotic, were compared with those of imipenem (IPM), flomoxef, cefuzonam (CZON) and cefotaxime. Sulopenem possessed broad-spectrum activities against Gram-positive bacteria and Gram-negative bacteria. Antibacterial activities of sulopenem against methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes and Streptococcus pneumoniae were equivalent to or somewhat superior to those of IPM. Against members of the family Enterobacteriaceae, sulopenem was 4- to 260-fold more active than reference antibiotics with broad-spectra. In a killing kinetics study for Haemophilus influenzae, sulopenem showed a 99.9% decrease of viable cells after 8 hours at a concentration of 0.20 micrograms/ml. This effect was obtained at a concentration 8-fold lower than that of IPM. The protective effects of sulopenem in murine experimental systemic infections were superior to those of imipenem/cilastatin. In murine experimental mixed infection with Escherichia coli and Bacteroides fragilis, sulopenem had lower ED50, in other words stronger antimicrobial activities than IPM. The therapeutic effect of sulopenem are related well with its MIC value. In guinea pigs experimental lung infection with Klebsiella pneumoniae, sulopenem was more effective than CZON or cefotiam.

Topics: Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; beta-Lactam Resistance; Cefotaxime; Ceftizoxime; Cephalosporins; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Guinea Pigs; Imipenem; Klebsiella Infections; Lactams; Lung Diseases; Mice; Mice, Inbred ICR; Thienamycins

The in vivo efficacies of piperacillin, piperacillin plus tazobactam, ticarcillin, ticarcillin plus clavulanic acid, piperacillin plus clavulanic acid, and cefotaxime were compared in a mouse model of pneumonia induced by the SHV-1 beta-lactamase-producer Klebsiella pneumoniae. Each antibiotic was injected either once intraperitoneally at 24 h postinfection or at repeated times during 24 h. The efficacies of the drugs and therapeutic protocols were assessed by counting viable bacteria recovered from the lungs of mice sacrificed at selected times. No emergence of beta-lactam-resistant organisms was detected. Ticarcillin at 300 mg/kg was ineffective. Repeated injections of piperacillin at 300 mg/kg, either alone or in combination with tazobactam (8:1), led to a significant decrease in bacterial counts, but this was followed by bacterial regrowth. The pharmacokinetic analysis demonstrated that this short-lasting antibacterial effect was not due to a failure of piperacillin and/or tazobactam to penetrate the lungs. The combinations of ticarcillin at 300 mg/kg plus clavulanic acid (15:1) and piperacillin at 300 mg/kg plus tazobactam (4:1) were proven to be effective in that they decreased the bacterial burden in the lungs from 10(5) to < 10(3) CFU. This dose effect of tazobactam can be explained by its dose-dependent penetration in the lungs. Cefotaxime at 100 mg/kg and the combination of piperacillin (slightly hydrolyzed by SHV-1) at 300 mg/kg plus clavulanic acid (15:1) led to the best efficacy. Both of these treatments induced a decrease in bacterial counts of nearly 4 log10 units. The survival rates correlated with the quantitative measurements of in vivo bacterial killing. These experimental results obtained from the restricted animal model used here may help in the design of further protocols for clinical trials.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefotaxime; Cephalosporins; Clavulanic Acid; Clavulanic Acids; Colony Count, Microbial; Drug Combinations; Drug Therapy, Combination; Female; Klebsiella Infections; Klebsiella pneumoniae; Lung; Mice; Microbial Sensitivity Tests; Penicillanic Acid; Penicillins; Piperacillin; Pneumonia, Bacterial; Tazobactam; Ticarcillin

A predominantly hospital-based outbreak of multiply-resistant Klebsiella pneumoniae capsular type K2 (MRK) expressing expanded spectrum betalactamase (ESBL) activity and fully sensitive only to the carbapenems and amikacin is described. The organism was isolated from 283 patients between March 1992 and September 1995. The outbreak started in the intensive care unit (ICU) of a major acute hospital and spread through surgical wards, a medical ward, a geriatric unit in a separate hospital and various other local hospitals. Environmental screening revealed extensive ward contamination. The decline of the outbreak after the spring of 1995 coincided with the re-emphasis of standard infection control procedures and the launch of a works programme aimed at addressing underlying sites of environmental contamination. Of the 283 cases, 166 (59.0%) were detected through a specially instigated case finding programme. The MRK caused 11 cases of septicaemia, two postoperative intra-abdominal abscesses, one case of postoperative meningitis, 102 cases of urinary tract infection and 28 wound infections and was isolated from the respiratory tracts of five patients with ventilator associated pneumonia. The difficulty in controlling the outbreak is ascribed to heavy environmental contamination, frequent inter- and intra-hospital patient transfers and prolonged carriage of the outbreak strain.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aztreonam; Cefotaxime; Ceftazidime; Cefuroxime; Cephalosporins; Ciprofloxacin; Costs and Cost Analysis; Disease Outbreaks; Drug Resistance, Microbial; Drug Resistance, Multiple; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Scotland

Transferable resistance to cefotaxime was demonstrated in 21 nosocomial strains of Klebsiella pneumoniae and Escherichia coli subsequently isolated from patients in two large University clinics. Using the double-disk diffusion test, we could detect, in each such strain, as well as in E. coli 3110 K-12 transconjugants after the transfer, the production of an Extended Spectrum Beta-Lactamase (ESBL). Ceftibuten was demonstrated to be effective against the majority of strains studied.

Topics: beta-Lactamases; Cefotaxime; Ceftibuten; Cephalosporins; Conjugation, Genetic; Cross Infection; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Humans; Hydrolysis; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Slovakia

The in vitro activity of cefodizime and two comparative cephalosporins, cefuroxime and ceftriaxone were studied against respiratory pathogens. MIC90s of cefodizime were 0.06-0.512 microgram/ml for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae. MIC50s of cefodizime for Klebsiella pneumoniae and Staphylococcus aureus isolates were 2 micrograms/ml and 8 micrograms/ml respectively. Cefuroxime and ceftriaxone at a concentration of 2 micrograms/ml and 1 microgram/ml inhibited 50% of Klebsiella pneumoniae and 50% of Staphylococcus aureus strains studied respectively. Cefodizime inhibited many of the important respiratory pathogens and can be suggested as an active antimicrobial agent for respiratory tract infections.

Topics: Cefotaxime; Ceftriaxone; Cefuroxime; Haemophilus Infections; Haemophilus influenzae; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae

During an 8-month period, Klebsiella pneumoniae resistant to cefotaxime and ceftazidime were isolated from 18 elderly patients in two closely-situated UK hospitals. Amongst these 18 patients, the organisms were isolated from urine samples of 17, from blood cultures of two and from a wound swab of one. The infected patients were located in nine different wards and several of the patients had been transferred between wards, within and between the two hospitals. All the bacterial isolates belonged to serotype K62, were non-typable or reacted only weakly with bacteriophage, showed similar plasmid profiles and were resistant to tetracycline and trimethoprim, thus indicating they were the same strain. Resistance to cefotaxime and ceftazidime was inhibited by clavulanic acid suggesting the involvement of extended-spectrum beta-lactamase (ESBL) enzyme activity. This was confirmed by analytical isoelectric focusing, which showed that isolates each produced two beta-lactamases with isoelectric points of 7.0(SHV-3) and 7.6 (SHV-1/2) respectively.

Topics: beta-Lactamases; Cefotaxime; Ceftazidime; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Species Specificity; United Kingdom

During a 3-week period, nine babies in the neonatal unit of a large teaching hospital in Durban were infected or colonized with Klebsiella pneumoniae resistant to a range of antimicrobial agents including amikacin and cefotaxime. Resistance to cefotaxime was reduced by clavulanic acid in vitro suggesting production of extended-spectrum beta-lactamase activity. All the isolates had the same antibiotic resistance profile, belonged to the same serotype (K17), were non-typable with bacteriophages, and had identical plasmid profiles indicating that they belonged to the same strain. During a 1-day microbiological survey of the ward, the outbreak strain was isolated from the nose and hands of a doctor based in the nursery and from the hands of a nurse and the mother of an infected baby. The strain was also isolated from nine of 67 environmental samples. Investigation revealed that infection control practices which had been instituted following a previous outbreak in the nursery with multi-resistant methicillin-resistant Staphylococcus aureus (MRSA) were not being adhered to. The re-introduction and strict enforcement of these procedures under the supervision of an Infection Control Nurse resulted in the abrupt end of the outbreak.

Topics: Amikacin; Carrier State; Cefotaxime; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Hospitals, Teaching; Humans; Infant; Infant, Newborn; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Methicillin Resistance; Microbial Sensitivity Tests; Nurseries, Hospital; South Africa

Klebsiella pneumoniae strain L 164 produces a penicillinase whose isoelectric point is 8.1, an unusual figure for this bacterial species. This strain exhibits resistance to conventional penicillins and a synergistic effect is seen with clavulanic acid. In contrast, susceptibility to cephalosporins is marked, as shown by the low minimum inhibitory concentrations (MICs). This phenotype is characteristic of strains with no acquired resistance. A first mutant with MICs for cephalothin and cefotaxime 8-fold to 16-fold those of the initial strain was obtained spontaneously. This mutant's MICs for the other beta-lactams were not substantially changed. In addition to the same penicillinase as the one produced by the parent strain, this mutant produced an acetyl-esterase capable of hydrolyzing the cephalosporins with an acetoxyl side-chain, i.e., cefalothin and cefotaxime, to deacetylated derivates which retain substantial antibacterial activity. Another mutant selected on an amoxicillin gradient produced ten times more penicillinase than the parent strain but no esterase. This second mutant exhibited very high MICs for penicillins and first and second generation cephalosporins. The MIC for cefotaxime was comparable to that seen with the esterase-producing mutant. Among the antimicrobials tested, only third generation cephalosporins and cefoxitin showed adequate activity.

Topics: Acetylesterase; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Cephalothin; Clavulanic Acid; Clavulanic Acids; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Penicillin Resistance; Penicillinase; Penicillins

A large perigraft abscess infected with Klebsiella sp. developed around a woven Dacron prosthesis inserted into a patient at high-risk with a leaking thoracoabdominal aortic aneurysm. Percutaneous insertion of a sump drainage catheter under ultrasound guidance accompanied by local and systemic antibiotic therapy was the only reasonable management option. Two years later the patient remains well with no evidence of sepsis on clinical examination, hematologic studies, computerized tomography or indium 111 labeled autologous leucocyte imaging. This technique may be successful in selected high-risk situations.

Topics: Aged; Amikacin; Aorta, Abdominal; Aorta, Thoracic; Blood Vessel Prosthesis; Catheterization; Cefotaxime; Drainage; Female; Humans; Klebsiella Infections; Polyethylene Terephthalates

Two isolates of Klebsiella pneumoniae possessing both TEM-1 and SHV-2 beta-lactamases were isolated from patients at the Cleveland Clinic in 1988. The beta-lactamases were discriminated and identified by using substrate hydrolysis data and an isoelectric focusing procedure in which the gel was overlaid with beta-lactamase inhibitors.

Topics: beta-Lactamase Inhibitors; beta-Lactamases; Cefotaxime; Ceftazidime; Drug Resistance, Microbial; Humans; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Ohio; Plasmids

Between 1986 and 1988, multiresistant Klebsiella pneumoniae strains exhibiting high-level cefotaxime resistance were isolated from patient specimens particularly of the intensive care units of the Aachen Technical University Hospital. The resistance gene responsible was shown to be encoded on a conjugative 66 kb plasmid designated pZMP1. The MIC values for cefotaxime of the original isolates and the transconjugants were greater than 128 mg l-1 and 64 mg l-1, respectively. Isoelectric focusing of protein preparations from the transconjugants showed a beta-lactamase with a pI of 7.6. A 3.6 kb BamHI fragment containing the beta-lactamase gene was cloned into pLG339 resulting in the recombinant plasmid pZMP1-1. A restriction map of the cloned insert was established and PstI subfragments of the insert were further subcloned into pBGS18. The nucleotide sequence of the complete 3.6 kb fragment was determined. Within 3663 bp an open reading frame of 858 kb was found to show 99% homology to the SHV-2 and -3 nucleotide sequences. The deduced amino acid sequence differed in one and two positions, respectively, from these established SHV enzymes. The 3' noncoding sequence exhibited nearly perfect homology to that of SHV-2, but the 5' upstream sequence showed homology of less than 50% to the corresponding SHV-2 sequence, indicating an altered promoter region of the variant SHV-enzyme. Kinetic analysis of the beta-lactamase revealed a 50-100% elevated hydrolytic effectivity on cefotaxime in comparison to other SHV enzymes. Cefoxitin, ceftazidime, aztreonam and imipenem were not hydrolysed by the enzyme. The variant enzyme was inhibited by commonly available beta-lactamase inhibitors. Clavulanic acid had the highest affinity for the enzyme and the greatest effectivity in blocking its action. Based on the genetic and kinetic data we propose to classify the enzyme as a new variant beta-lactamase of the SHV-type and name it SHV-2a.

Topics: Base Sequence; beta-Lactamases; Cefotaxime; Cloning, Molecular; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Microbial; Humans; Isoelectric Focusing; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Open Reading Frames; Plasmids; Restriction Mapping; Sequence Homology, Nucleic Acid

In 1983 our antibiotic regimen for suspected neonatal septicemia was changed from amoxicillin-gentamicin to cefotaxime-amoxicillin. During the subsequent 5-year period we studied the effect of this change in regimen on the bacterial flora of the infants in the unit and the occurrence of serious infections. This was done with bacteriologic surveillance and analysis of the positive blood cultures from 1978 through 1987. A change in the relative numbers of isolated pathogens was observed; Klebsiella sp. and Escherichia coli decreased whereas Enterobacter sp. increased. The susceptibility of the Enterobacter isolates to cefamandole decreased from 85.3% in 1982 to 52.9% in 1983. The susceptibility of these bacteria to cefotaxime was 55.2% in 1983 and 55.0% in 1987. No change in susceptibilities to cefotaxime, amoxicillin or gentamicin was found in other pathogens. Although colonization with Enterobacter strains has increased and the susceptibility of these bacteria to the cephalosporins has decreased, the incidence of serious infections with Gram-negative bacteria decreased.

Topics: Amoxicillin; Cefotaxime; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gentamicins; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Male; Sepsis

We reviewed cases of Gram-negative enteric bacillary meningitis in infants and children treated with cefotaxime at Texas Children's Hospital from January, 1984, through June, 1989. Seventeen of 20 children had an underlying condition predisposing to the development of meningitis. The etiologic organisms in these 20 children (2 days to 12 years old; median, 12 days old) were Klebsiella sp, 9; Escherichia coli, 4; Enterobacter cloacae, 3; Citrobacter diversus, 2; other, 2. With the exception of one isolate of Acinetobacter, all isolates were susceptible to cefotaxime. In addition to cefotaxime 17 children received an aminoglycoside intravenously. Children with meningitis caused by Klebsiella sp. or non-Klebsiella organisms received cefotaxime for 31 +/- 14 and 37 +/- 17 days, respectively. Aminoglycosides were administered for 16 +/- 10 days in both groups. Five children in each group also received intraventricular doses (1 to 25) of an aminoglycoside (9) or colistimethate (1). The mean durations of positive lumbar, ventricular cerebrospinal fluid or brain abscess cultures were 5.8 +/- 4.7 and 7.2 +/- 5.0 days after start of therapy in the Klebsiella and non-Klebsiella meningitis patients, respectively. Only three children were normal at the time of discharge or follow-up. Gram-negative enteric meningitis remains difficult to treat despite the excellent in vitro activity of cefotaxime against Gram-negative enterics, in part as a result of the predisposing conditions resulting in the development of this infection.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Citrobacter; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Infant; Infant, Newborn; Klebsiella Infections; Meningitis; Retrospective Studies

Topics: Cefotaxime; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged

A significant decrease in resistance to infections caused by gramnegative pathogens was observed in mice with neutropenia induced by cytostatics. Efficacy of schemes for combined chemotherapy with beta-lactams, aminoglycosides and a novel peptide antibiotic was studied on model infections in mice with neutropenia. In the neutropenic mice with sepsis caused by Pseudomonas the peptide antibiotic administered parenterally in a single dose of 50 micrograms/kg provided high therapeutic activity. In combination with azlocillin, cefotaxime and amikacin the peptide antibiotic has a synergistic therapeutic action.

Topics: Agranulocytosis; Amikacin; Animals; Azlocillin; Cefotaxime; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Immune Tolerance; Klebsiella Infections; Mice; Neutropenia; Opportunistic Infections; Pseudomonas Infections

We report a rare case of Klebsiella pneumoniae meningitis associated with liver abscess, which was successfully treated with cefotaxime (CTX), one of the third-generation cephalosporins. A 53-year-old man was admitted to Keio University Hospital on June 13, 1988, because of a fever and a headache. On June 3, he suddenly started shivering and his temperature rose to 39 degrees C. He then began to complain of polydipsia, polyuria, and a weight loss of 4 kg a week. On June 11, he developed a severe headache. Four years prior to this incident, he had been diagnosed as having diabetes after a routine medical examination, but had neglected to undergo medical treatment. On admission, laboratory data showed leukocytosis, hyperglycemia (394 mg/dl) and ketonuria (4+). A lumbar puncture yielded cloudy cerebrospinal fluid (CSF) containing 500/3 cells/mm8, of which about 70% were neutrophils. A diagnosis of diabetic ketoacidosis and purulent meningitis was made. A treatment with ampicillin (ABPC) and CTX, (12 g/day, each) was begun. On the third day, cultures of a blood specimen and CSF yielded both K. pneumoniae. The MICs of CTX to K. pneumoniae isolated from blood and CSF were both 0.05 microgram/ml. ABPC was discontinued, gentamicin was administered for 2 days, CTX was continued at the same dosage level and an administration of prednisolone 40 mg daily was begun.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cefotaxime; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Meningitis; Middle Aged; Sepsis

In Klebsiella pneumoniae 86-4, cefotaxime resistance was due to a transferable broad-spectrum beta-lactamase, SHV-3. The plasmid-borne gene encoding SHV-3 has been cloned, and the primary structure of the enzyme was deduced from its nucleotide sequence. SHV-3 differs from SHV-1 in two positions. The extended substrate profile of SHV-3 probably results from the substitution of Ser-213 for Gly, as in SHV-2, whereas replacement of Arg-180 by Leu resulted in a decrease in the pI from 7.6 to 7.0. The blashv-3 gene is highly homologous (92% DNA sequence identity) with the chromosomal gene coding for LEN-1 beta-lactamase of K. pneumoniae, suggesting that the origin of the SHV-encoding genes now present on many plasmids may be chromosomal.

Topics: Base Sequence; beta-Lactamases; Cefotaxime; Cloning, Molecular; Cross Infection; Culture Media; Drug Resistance, Microbial; Electrophoresis, Agar Gel; Escherichia coli; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Plasmids; Restriction Mapping

A 60-year-old woman with rheumatoid arthritis developed acute emphysematous septic arthritis of the knee due to Klebsiella pneumoniae. She was brought to the hospital in septic shock with disseminated intravascular coagulation and had striking physical signs and roentgenograms showing distention of the knee with gas. She also had an infection of the hand with subcutaneous gas. After surgical drainage and institution of antibiotic therapy, she remained critically ill for several days but gradually improved. Two months later, she was ambulating independently. Emphysematous septic arthritis is rare. Four cases have previously been reported, but none were caused by Klebsiella.

Topics: Arthritis, Infectious; Cefotaxime; Emphysema; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Knee Joint; Middle Aged; Radiography; Shock, Septic

Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low-level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated urinary tract infection, but failed in major infections at other sites. 1-5 mg/l of the beta-lactamase inhibitors clavulanic acid or sulbactam restored normal activity to cefotaxime against the multiresistant strains. Resistance to third-generation cephalosporins was mediated by a new broad-spectrum enzyme of isoelectric point 6.3. Resistance to beta-lactams and aminoglycosides was transferable to Escherichia coli. The emergence of transferable enzymatic resistance to newer beta-lactams in K pneumoniae strains indicates a major risk of spread of such resistance to otherwise sensitive strains.

Topics: Amikacin; beta-Lactamases; Cefotaxime; Cephalosporins; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Enterobacteriaceae; Escherichia coli; Humans; Klebsiella Infections; Klebsiella pneumoniae; Paris; Recurrence; Urinary Tract Infections

Information on 62 bacteriologically confirmed cases of bacterial meningitis treated with cefotaxime in this country was obtained retrospectively from infectious disease consultants. This series of cases differed markedly from the world cumulative case data thus far presented. One of the two most common organisms treated was the pneumococcus (allergy to penicillin or misdiagnosis of the Gram stain results were the major reasons given). The other organism was Klebsiella. Unanticipated bacteriologic successes were noted in two cases of staphylococcal meningitis secondary to parameningeal foci. The bacteriologic cure rate and survival rate were about 85 percent. Failure of monotherapy was seen in one case of Pseudomonas meningitis, as well as in three of five cases of Enterobacter meningitis. In addition, two cases of Escherichia coli meningitis in which moxalactam therapy inexplicably failed were cured with cefotaxime. Close analysis of killing kinetics appeared to explain the Enterobacter and E. coli failures. Thus, overall not all gram-negative species and not all isolates of any particular species that cause meningitis can be successfully treated by cephalosporins. Data obtained during the investigative trials do not appear to be entirely predicative of what occurred during the free clinical use of an antibiotic. Post-investigatory follow-up and surveillance of all newly introduced therapeutic agents are needed.

Topics: Adult; Aged; Bacterial Infections; Cefotaxime; Escherichia coli; Escherichia coli Infections; Humans; Infant, Newborn; Klebsiella Infections; Male; Meningitis; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Moxalactam

The activity of ceftazidime was examined in a murine model of Klebsiella pneumoniae pneumonia in which the antibiotic was administered subcutaneously 6 h after intranasal infection and then twice daily for the next three days (i.e. seven doses). In a series of experiments using this test, the dose of ceftazidime giving 50% survival relative to controls (SD50) ranged from 1.0-9.0 mg/kg/dose while the dose required to reduce the log10 cfu/lung by 50% (CD50) ranged from 24-64 mg/kg/dose. Ceftazidime was considerably more effective than cefotiam, amoxycillin-clavulanic acid or kanamycin in the test. Pharmacokinetic studies with ceftazidime showed that no differences in respiratory tract penetration existed between uninfected mice and mice infected for 48 h with K. pneumoniae. The percentage penetration of ceftazidime from serum was 73% for pleural fluid, 44% for tracheal fluid, 27% for tracheal wall tissue and 17% for whole lung tissue after a subcutaneous injection of 100 mg/kg. At this dose, ceftazidime remained at supra-MIC concentrations for 2-3 h in all compartments examined.

Topics: Amoxicillin; Animals; Body Fluids; Cefotaxime; Cefotiam; Ceftazidime; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Female; Kanamycin; Klebsiella Infections; Klebsiella pneumoniae; Lung; Mice; Pleura; Pneumonia; Tissue Distribution; Trachea

We have described a patient with Klebsiella pneumoniae meningitis who was treated with cefotaxime and chloramphenicol concomitantly, and whose slow initial resolution and subsequent relapse plus in vitro evidence of antagonism of cefotaxime appear to indicate that chloramphenicol interfered with the activity of the cephalosporin. Thus, concomitant use of chloramphenicol should probably be avoided or used advisedly in adults with gram-negative bacillary meningitis susceptible to a third generation cephalosporin.

Topics: Brain Diseases; Cefotaxime; Chloramphenicol; Creutzfeldt-Jakob Syndrome; Cysts; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Middle Aged; Surgical Wound Infection

An outbreak of serious infections due to gentamicin-resistant Klebsiella pneumoniae occurred in a neonatal intensive care unit in which the combination of gentamicin sulfate and ampicillin sodium had been used for standard initial therapy for suspected sepsis for nearly 11 years. After institution of control measures that included the substitution of cefotaxime sodium for gentamicin in the standard regimen, the outbreak promptly subsided. Nevertheless, a second outbreak of serious infections due to cefotaxime-resistant Enterobacter cloacae began ten weeks later. Sequential stool cultures from patients in the unit confirmed the disappearance of gentamicin-resistant K pneumoniae and the emergence of cefotaxime-resistant E cloacae after the change in antibiotic policy. These observations suggest that routine use of newer cephalosporins for therapy of suspected sepsis may lead to the emergence of drug-resistant microorganisms more rapidly than has occurred with the aminoglycosides.

Topics: Ampicillin; Cefotaxime; Cross Infection; Disease Outbreaks; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Gentamicins; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Penicillin Resistance; South Carolina; Time Factors

The in vivo activity of cefodizime (HR 221) was compared with that of cefotaxime (CTX), cefmenoxime, latamoxef, cefazolin and cefmetazole (CMZ). The protective effects of HR 221 on experimental infections in mice caused by Staphylococcus aureus Smith, Escherichia coli C-11, Proteus vulgaris GN-76 and Serratia marcescens No. 2 were directly related to its in vitro activity against these strains. In contrast, the compound showed the smallest ED50 values, among the 5 antibiotics tested (not including CMZ), for Klebsiella pneumoniae 3K-25 and Pseudomonas aeruginosa PI 67 against which it had relatively low in vitro activity, and its ED50 for Citrobacter freundii GN-346 was as small as 1.821 mg/mouse in spite of its MIC of greater than 100 micrograms/ml. HR 221 exerted potent bactericidal activity against Streptococcus pneumoniae Sp-1 inoculated into the mouse lung; the duration of action was prolonged. When tested against the E. coli Ec-89 infection induced in the rat uterus, the activity of HR 221 given to rats once daily was equal to that of CTX or CMZ given at the same dose twice daily.

Topics: Animals; Cefmetazole; Cefotaxime; Cephamycins; Klebsiella Infections; Male; Mice; Mice, Inbred ICR; Rats; Rats, Inbred Strains; Staphylococcal Infections; Streptococcal Infections

We treated 12 adult patients who had gram-negative bacillary meningitis with cefotaxime administered intravenously at a dose of 2 g every 4 hours. The etiological organisms included Haemophilus influenzae (3 cases), Serratia marcescens (3 cases), Klebsiella pneumoniae (3 cases), Escherichia coli (2 cases), and Enterobacter (1 case). The infection followed a neurosurgical procedure in 6 cases. The mean inhibitory and bactericidal concentrations of cefotaxime for the isolates ranged from 0.125 to 0.25 microgram/ml. The cerebrospinal fluid (CSF) concentrations of cefotaxime ranged from 5.0 to 15.2 micrograms/ml, and the CSF bactericidal titers were 1:64 to 1:128. The CSF in all patients was sterilized within 96 hours. All 12 patients recovered, and there were no relapses.

Topics: Adult; Bacterial Infections; Cefotaxime; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meningitis; Meningitis, Haemophilus; Middle Aged; Serratia marcescens

A man who presented with lumbar backache subsequently developed signs of meningitis. The causative organism was proved to be Klebsiella pneumoniae. Despite treatment with chloramphenicol and amikacin, the condition progressed until cefotaxime was added to the treatment regimen. The patient made a good recovery. This is the first report of the use of cefotaxime in klebsiella meningitis.

Topics: Back Pain; Cefotaxime; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Middle Aged

The authors report on the successful cefotaxime treatment (one of the newer cephalosporins) of K. pneumoniae meningitis which developed while the patient was under treatment with an older cefalosporin, cephalothin.

Topics: Adolescent; Cefotaxime; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis

Topics: Adult; Cefotaxime; Cerebrospinal Fluid; Drug Resistance, Microbial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meningitis; Recurrence

The efficacies of several dosage schedules of cefazolin, cefotaxime, and ceftazidime, started 12 or 36 h after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae in rats. The therapeutic activities of the cephalosporins were compared with the antibacterial activities in vitro and the serum concentration curves. The course of experimental pneumonia was rapid and characterized by tissue necrosis. Response to antimicrobial treatment was evaluated with respect to mortality and numbers of bacteria in lung (left lobe), blood, and pleural fluid. When antibiotic treatment was started early, i.e., 12 h after bacterial inoculation, cefotaxime and ceftazidime were equally effective and superior to cefazolin. Eleven doses of 10 mg of cefotaxime or ceftazidime per kg or 11 doses of 60 mg of cefazolin per kg were required to improve the survival rate. With a delay in administration to 36 h after inoculation, the efficacy of the cephalosporins decreased markedly. In the three dosages tested, cefazolin was ineffective. Survival improved with the administration of nine doses of 60 mg of cefotaxime per kg or nine doses of 10 mg of ceftazidime per kg. These results are not in accordance with the ratio of in vitro activities of cefotaxime and ceftazidime or the serum concentration curves.

Topics: Animals; Cefazolin; Cefotaxime; Ceftazidime; Cephalosporins; Female; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Rats

The therapeutic efficacy of ceftriaxone and gentamicin was investigated in a foreign body induced abscess model in the rat by implanting a dialysis tube contaminated with Klebsiella pneumoniae into the subcutaneous tissue. Animals were treated for four days with ceftriaxone, gentamicin, and their combination starting immediately following or 48 h after the implantation. Peak free ceftriaxone and gentamicin abscess fluid levels were 4.3 and 2.6 mcg/ml, which were 7.3% and 37.5% of peak blood levels respectively. Both agents persisted longer in abscess fluid than in blood. Ceftriaxone inhibited the development of abscess formation when administered shortly after the implantation of the contaminated foreign body whereas gentamicin alone was without beneficial effect. When administered after 48 h ceftriaxone was less effective than immediately after implantation and gentamicin was again without any therapeutic effect. The effect of the combination of ceftriaxone and gentamicin was slightly better than ceftriaxone alone. Low oxygen tension may be an explanation for the lack of bactericidal effect of gentamicin. Ceftriaxone may be more suitable for the therapy of closed space infections caused by susceptible microorganisms than gentamicin.

Topics: Abscess; Animals; Cefotaxime; Ceftriaxone; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Gentamicins; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Male; Rats; Rats, Inbred Strains

The effect of cefotiam and cefazolin on the ultrastructure of Klebsiella pneumoniae DT-S in vitro and in experimental pneumonia in mice was examined by electron microscopy. The action of both cephalosporins against K. pneumoniae DT-S was bactericidal, and a dose response in the action was definite. At the minimal inhibitory concentration of each cephalosporin, filamentation of the cells was induced and the cytoplasm became sparse during the course of incubation. With elevation of the concentration of the cephalosporins, spheroplasts were formed; they subsequently collapsed. In the lungs of mice, the infecting organisms localized in the alveolar space, and each cell was connected by a threadlike material. A fibrous matrix, located on the cell surface of the infecting organisms, was observed in ultrathin sections. By administration of each cephalosporin to mice, several morphological changes, similar to those noted in vitro, were observed in the infecting organisms.

Topics: Animals; Cefazolin; Cefotaxime; Cefotiam; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Mice; Mice, Inbred ICR; Microscopy, Electron; Microscopy, Electron, Scanning; Pneumonia

The MICs of cefotiam and cefazolin against K. pneumoniae DT-S were unaffected by the inoculum size and were 0.1 and 1.56 micrograms/ml, respectively. Bactericidal and bacteriolytic activities of the cephalosporins were more potent in bacterial concentrations of 10(7) colony-forming units (CFU)/ml than in concentrations of 10(8) CFU/ml. Both activities of cefotiam were more markedly influenced by bacterial concentrations than those of cefazolin. Therapeutic activity of cefotiam was about 9 approximately 15 times as potent as that of cefazolin in experimental pneumonia caused by K. pneumoniae DT-S in mice, and this finding was in accordance with the ratio of in vitro antibacterial activities of the two cephalosporins as judged by the MICs or the bactericidal and bacteriolytic activities in bacterial suspension of 10(7) CFU/ml. The range of concentrations of cefotiam which induced cell filamentation in vitro, was wider than that of cefazolin. This difference, however, was not reflected on the therapeutic activities of the two cephalosporins in the model infection. In the pneumonic lungs, definite therapeutic doses of both cephalosporins (80 mg of cefotiam per kg and 640 mg of cefazolin per kg) produced mainly bacteriolysis of the challenge organisms.

Topics: Animals; Anti-Bacterial Agents; Cefazolin; Cefotaxime; Cefotiam; Drug Resistance, Microbial; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Pneumonia