cefoxitin and Klebsiella-Infections

To investigate the susceptibility and specificity of the phenotypic methods to determine plasmidmediated AmpC.. The cross-sectional study was conducted at Duzce University Faculty of Medicine, Microbiology Laboratory from January 2015 to June 2016, and comprised Escherichia coli and Klebsiella pneumonia isolates intermediate susceptible or resistant to cefoxitine. Combined disk diffusion test, double disc synergy test, agar gradient test and polymerase chain reaction were used to detect plasmid-mediated AmpC.. Of the 2024 E. coli samples, 44(2.17%), and of the 792 K. pneumoniae samples, 16(2%) were included. Combined disk diffusion test had susceptibility of 68% and specificity of 50%; double disc synergy test 24% and 82%; and agar gradient test 40% and 68%. Of the isolates positively detected by polymerase chain reaction method, more than one gene region positivity was detected in 15(25%) isolates.. All three phenotypic methods were found to be insufficient to detect plasmid-mediated AmpC positivity.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefoxitin; Cross-Sectional Studies; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Plasmids

The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefoxitin; Cross Infection; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Humans; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Pilot Projects; Prospective Studies; Prostatitis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

To determine the burden of AmpC beta-lactamase producing Klebsiella pneumoniae and its antimicrobial profile among paediatric patients.. This cross-sectional study was conducted at the Microbiology Department of The Children's Hospital and the Institute of Child Health in Lahore, Pakistan, from May 2014 to April 2015, in which isolates of Klebsiella pneumoniae were screened by using the cefoxitin disc. Confirmation was done by inhibitor-based method using 400 micro grams of boronic acid dispensed on the cefoxitin discs. The zone sizes of cefoxitin with and without the boronic acid were compared. The antimicrobial susceptibility testing was performed using Kirby Bauer disc diffusion method.. Positive cultures yielded 585 Klebsiella pneumoniae out of which 220(37.6%) strains were AmpC beta-lactamase-positive on the basis of cefoxitin screening and 126(21.53%) were positive on the basis of inhibitor-based confirmatory method. Most of the infected patients 73(57.9%) were neonates. All AmpC beta-lactamase-producing strains were resistant to cephalosporins. They also exhibited resistance to ciprofloxacin 109(86.5%), amikacin 98(77.8%), levofloxacin 8(77.8%), cefoperazone-sulbactam 81(64.3%), piperacillin-tazobactam 82(65.1%), meropenem, 56(44.4%) and imipenem 32(25.4%).. Prompt identification of AmpC beta-lactamases using inhibitor-based confirmatory test can help reduce the burden of these pathogens.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefoperazone; Cefoxitin; Cephalosporins; Child; Child, Preschool; Ciprofloxacin; Cross-Sectional Studies; Disk Diffusion Antimicrobial Tests; Drug Combinations; Drug Resistance, Bacterial; Female; Hospitals, Pediatric; Humans; Imipenem; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Pakistan; Piperacillin, Tazobactam Drug Combination; Sulbactam

Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL.. We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria.. We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment.. Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefoxitin; Drug Eruptions; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prospective Studies; Treatment Outcome; Urinary Tract Infections; Uropathogenic Escherichia coli

OmpK35 and OmpK36 are the major outer membrane porins of Klebsiella pneumoniae. We aimed to study the effect of combined porin loss and production of extended-spectrum β-lactamases (ESBLs) on imipenem susceptibility among K. pneumoniae clinical isolates.. This study included 91 suspected ESBL-producing K. pneumoniae clinical isolates, isolated from different patient specimens at the Cairo University hospital from January to June 2010. All isolates were subjected to genotypic analysis of the outer membrane protein gene expression using reverse transcription-PCR (RT-PCR) and analysis of OmpK35/36 of 38 isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).. By RT-PCR, loss of Omp35 was detected in 78 (85.7%) isolates, loss of Omp36 was detected in 64 (70.32%), and loss of both porins was detected in 62 (68.1%). Out of 91 isolates, 45 (49.5%) were resistant to cefoxitin, and 17 (18.7%) were confirmed as derepressed AmpC producers. Omp35 was lost in all FOX-resistant isolates, whereas Omp36 was lost in 42 (93.3%) (p-value 0.002). The mean of ceftazidime inhibition zone diameter was significantly decreased among ESBL-producing isolates with loss of Omp35/36 (p-value 0.041 and 0.006), respectively. The mean of imipenem minimal inhibitory concentration (MIC) was markedly increased to 8.55 μg/ml among AmpC-producing isolates with Omp35/36 loss, while the mean of imipenem MIC among the 66 confirmed ESBL producers was 0.32 μg/ml.. Imipenem MIC was markedly increased among K. pneumoniae isolates showing AmpC production with loss of both porins OmpK35/36. Meanwhile, the association of porin OmpK35/36 loss with ESBL production was not a direct cause of resistance to imipenem.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefoxitin; Egypt; Gene Expression Regulation, Bacterial; Hospitals, University; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Porins

Cefoxitin has demonstrated in vitro resistance to hydrolysis by extended-spectrum beta-lactamases.. We evaluated the microbiological and clinical efficacy of cefoxitin in 33 patients treated for an infection related to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). Clinical and microbiological outcomes were assessed from the initiation of cefoxitin therapy to the latest information available in the patient's medical file.. The 33 patients were mainly males (n = 26), aged 70 years (median, minimum-maximum: 23-93) and main sites of infection were urinary (n = 23) and catheter-related bloodstream infections (n = 4). Escherichia coli and Klebsiella pneumoniae were isolated in 19 and 14 subjects, respectively. The clinical outcome was favorable in 30 of 33 patients in the first 48 h after the start of cefoxitin, and in 20 (of 24 evaluable) at the end of follow-up. Six microbiological failures were documented and resistance to cefoxitin emerged in two strains of K. pneumoniae.. Cefoxitin could be considered as a carbapenem-sparing antibiotic for some ESBL-E infections, preferentially those related to E. coli.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefoxitin; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome; Young Adult

Klebsiella pneumoniae is an important pathogen, increasingly notorious for its ability to become resistant to antimicrobial agents. This study sought to characterize trends in antimicrobial susceptibility rates for K. pneumoniae causing bacteremias across the United States (U.S.) Veterans Healthcare Administration (VHA) from 2007 through 2013 utilizing a national clinical database. K. pneumoniae grew in 9,235 blood cultures from 8,414 patients. Nationally, ampicillin-sulbactam, ceftazidime, cefepime, ertapenem, fluoroquinolones, and amikacin demonstrated statistically significant susceptibility rate increases against K. pneumoniae in the 2010-2013 period versus the 2007-2009 period. No antimicrobial agent had a statistically significant nationwide susceptibility rate decrease. Of the 126 antibiotic-organism pairs tested among 9 U.S. regions, 18 demonstrated statistically significant susceptibility rate increases while 6 demonstrated statistically significant susceptibility rate decreases. The East North Central (eight agents), Mid-Atlantic (five agents), and South Atlantic (four agents) regions demonstrated statistically significant susceptibility rate increases for multiple antimicrobial agents. Of the 70 antibiotic-organism pairs tested among 5 different medical center complexity levels, 11 antibiotics demonstrated statistically significant susceptibility rate increases and 1 demonstrated a statistically significant rate decrease. Extended-spectrum β-lactamase production did not significantly change over the study period across an available nationwide representation of 31 facilities (10.6% in 2007-2009 vs. 9.21% in 2010-2013, p=0.17). The South Atlantic and Mid-Atlantic regions had the highest prevalence of extended-spectrum ß-lactamase production in the two periods, respectively. The recent trend of generally increasing susceptibility rates for K. pneumoniae bloodstream isolates in this nationwide U.S. VHA study contrasts from other U.S. health system reports demonstrating increasing trends of antimicrobial resistance.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Cefepime; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Ertapenem; Fluoroquinolones; Gene Expression Regulation, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sulbactam; United States; United States Department of Veterans Affairs

The aim of the study was to identify risk factors associated with pre-transplant fecal carriage of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in liver transplant recipients.. Over a 3-year period (January 2009-December 2011), 317 patients who underwent liver transplantation were screened preoperatively for fecal carriage of ESBL-producing Enterobacteriaceae. Risk factors for fecal carriage were investigated by univariate analysis and stepwise logistic regression.. Of the 317 patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous infection with an ESBL-producing organism had developed during the last 6 months in 20% of fecal carriers versus in none of the non-carriers. Other variables associated with fecal carriage were a model for end-stage liver disease score ≥25, pre-transplant stay in the intensive care unit ≥48 h, hospital stay ≥10 days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP), exposure to a β-lactam agent in the last month, and prophylaxis with norfloxacin. Independent predictors of fecal carriage in the multivariate logistic regression model were exposure to a β-lactam agent in the month preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4-15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02).. Previous infection with an ESBL-producing isolate, recent exposure to a β-lactam agent, and a history of SBP are risk factors for preoperative fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant recipients. Patients at risk of fecal carriage should receive intraoperative prophylaxis and, when necessary, empiric postoperative antimicrobial treatment that includes coverage for these organisms.

Topics: Adult; Amikacin; beta-Lactamases; beta-Lactams; Cefoxitin; Ciprofloxacin; Drug Resistance, Bacterial; End Stage Liver Disease; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Feces; Female; Humans; Imipenem; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Preoperative Period; Risk Factors; Severity of Illness Index

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

Clinical isolates of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains are being increased worldwide. Five pan-resistant K. pneumoniae strains have been isolated from respiratory and ICU wards in a Chinese hospital, and reveal strong resistance to all β-lactams, fluoroquinolones and aminoglycosides. Totally 27 β-lactamase genes and 2 membrane pore protein (porin) genes in 5 K. pneumoniae strains were screened by polymerase chain reaction (PCR). The results indicated that all of 5 K. pneumoniae strains carried blaTEM-1 and blaDHA-1 genes, as well as base deletion and mutation of OmpK35 or OmpK36 genes. Compared with carbapenem-sensitive isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the resistant isolates markedly lacked the protein band of 34-40 kDa, which might be the outer membrane proteins of OmpK36 according to the electrophoresis mobility. In addition, the conjugation test was confirmed that blaDHA-1 mediated by plasmids could be transferred between resistant and sensitive strains. When reserpine (30 μg/mL) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (50 μg/mL) were added in imipenem and meropenem, the MICs had no change against K. pneumoniae strains. These results suggest that both DHA-1 β-lactamase and loss or deficiency of porin OmpK36 may be the main reason for the cefoxitin and carbapenem resistance in K. pneumoniae strains in our hospital.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cefoxitin; China; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Polyacrylamide Gel; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Weight; Polymerase Chain Reaction; Porins

Cefoxitin-resistant Escherichia coli (n = 109) and Klebsiella pneumoniae (n = 16) isolates collected from patients in India in 2009 to 2010 were screened for bla(ampC) families and mobilizing elements (ISEcp1, IS26, ISCR1, and sul-1-type class 1 integrons) and their association with bla(ampC) and for the occurrence of class A beta-lactamases (BLs) (CTX-M, TEM, and SHV). The concurrent occurrences of two distinct AmpC families (bla(CIT) and bla(EBC)) and of class A with class C beta-lactamase were observed. All but one of the isolates harboring CTX-M extended-spectrum BLs (ESBLs) were carrying bla(CTX-M) genogroup 1; the remaining isolate carried bla(CTX-M) genogroup 9. The mobilizing elements occurred in different combinations in the study isolates.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefoxitin; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; India; Integrons; Interspersed Repetitive Sequences; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Sequence Analysis, DNA

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Catheter-Related Infections; Cefoxitin; Cross Infection; Diarrhea; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecalis; Glycopeptides; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pancreatic Neoplasms; Pneumonia, Bacterial; Postoperative Complications; Prostatitis; Substrate Specificity; Urinary Catheterization

OmpK35 and OmpK36 are the major outer membrane porins of Klebsiella pneumoniae. In this study, a virulent clinical isolate was selected to study the role of these two porins in antimicrobial resistance and virulence. The single deletion of ompK36 (ΔompK36) resulted in MIC shifts of cefazolin, cephalothin, and cefoxitin from susceptible to resistant, while the single deletion of ompK35 (ΔompK35) had no significant effect. A double deletion of ompK35 and ompK36 (ΔompK35/36) further increased these MICs to high-level resistance and led to 8- and 16-fold increases in the MICs of meropenem and cefepime, respectively. In contrast to the routine testing medium, which is of high osmolarity, susceptibility tests using low-osmolarity medium showed that the ΔompK35 mutation resulted in a significant (≥ 4-fold) increase in the MICs of cefazolin and ceftazidime, whereas a ΔompK36 deletion conferred a significantly (4-fold) lower increase in the MIC of cefazolin. In the virulence assays, a significant (P < 0.05) defect in the growth rate was found only in the ΔompK35/36 mutant, indicating the effect on metabolic fitness. A significant (P < 0.05) increase in susceptibility to neutrophil phagocytosis was observed in both ΔompK36 and ΔompK35/36 mutants. In a mouse peritonitis model, the ΔompK35 mutant showed no change in virulence, and the ΔompK36 mutant exhibited significantly (P < 0.01) lower virulence, whereas the ΔompK35/36 mutant presented the highest 50% lethal dose of these strains. In conclusion, porin deficiency in K. pneumoniae could increase antimicrobial resistance but decrease virulence at the same time.

Topics: Animals; Bacterial Proteins; Cefepime; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Genetic Complementation Test; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Sequence Data; Phagocytosis; Porins; Sequence Analysis, DNA; Thienamycins; Virulence

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

A clinical Klebsiella pneumoniae isolate carrying the extended-spectrum beta-lactamase gene variants bla(SHV-40), bla(TEM-116) and bla(GES-7) was recovered. Cefoxitin and ceftazidime activity was most affected by the presence of these genes and an additional resistance to trimethoprim-sulphamethoxazole was observed. The bla(GES-7) gene was found to be inserted into a class 1 integron. These results show the emergence of novel bla(TEM) and bla(SHV) genes in Brazil. Moreover, the presence of class 1 integrons suggests a great potential for dissemination of bla(GES) genes into diverse nosocomial pathogens. Indeed, the bla(GES-7) gene was originally discovered in Enterobacter cloacae in Greece and, to our knowledge, has not been reported elsewhere.

Topics: Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Brazil; Cefoxitin; Ceftazidime; DNA, Bacterial; Female; Humans; Integrons; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Sequence Analysis, DNA; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefoxitin; Ceftazidime; Cephalosporin Resistance; Critical Care; Cross Infection; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Phenotype; Retrospective Studies; Taiwan

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

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

The beta-lactam antibiotics, in combination with aminoglycosides, are among the most widely prescribed antibiotics. However, because of extensive and unnecessary use, resistance to these drugs continues to increase. In recent years, resistance in the Indian bacterial population has increased markedly, the majority showing complex mechanisms. Due to increased transcontinental movement of the human population, it would be wise to know the prevalence and resistance complexity of these strains, well in advance, in order to formulate a policy for empirical therapy.. One hundred and eighty-one isolates of Escherichia coli and 61 isolates of Klebsiella pneumoniae obtained from 2655 non-repeat samples of pus (912) and urine (1743) were studied, and their resistance rates and patterns were noted. The isolates were analyzed for prevalent aminoglycoside and cephalosporin resistance phenotypes and for the presence of extended spectrum beta-lactamase (ESBL) and AmpC enzymes by spot-inoculation and modified three-dimensional tests developed in our laboratory. Fourteen isolates of E. coli and six of K. pneumoniae, resistant to all of the antibiotics tested, were selected for plasmid screening, curing, and transconjugation experiments, and for comparative evaluation of the double disk synergy test (DDST) and modified three-dimensional test (TDT) for detection of beta-lactamases.. Urinary E. coli isolates showed maximum susceptibility to amikacin (57.1%), followed by tobramycin (38.5%) and gentamicin (31.9%). Eighteen (19.8%) isolates were susceptible to cefotaxime, whereas 11 (12.1%) were susceptible to ceftriaxone. The K. pneumoniae isolates from urine samples showed maximum susceptibility to tobramycin (63.6%) followed by amikacin (54.5%). Of the K. pneumoniae isolates, 31.8% were susceptible to cefotaxime and 13.6% were susceptible to ceftriaxone. A more or less similar trend of antibiotic susceptibility was noted in E. coli and K. pneumoniae isolates from pus samples. Twenty-six (14.4%) E. coli and 15 (24.6%) K. pneumoniae isolates were found to be ESBL-producers by NCCLS-ESBL phenotypic confirmatory test. Eighteen (9.9%) E. coli and 19 (31.1%) K. pneumoniae isolates were found to be AmpC enzyme-producers by our modified TDT. The simultaneous occurrence of ESBL and AmpC enzymes was noted in 7.7% and 9.8% isolates of E. coli and K. pneumoniae, respectively.. The prevalence of multidrug-resistant bacterial isolates is quite high in our bacterial population. On comparative evaluation of DDST and TDT in resistant isolates, TDT was found to be the better method, detecting ESBLs in 80% of isolates compared to 15% with DDST. A 19.9-kb plasmid was consistently present in all the screened isolates of E. coli and K. pneumoniae, and was inferred to encode cefoxitin and tetracycline resistance based on curing and transconjugation experiments.

Topics: Academic Medical Centers; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefoxitin; Cephalosporin Resistance; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Prevalence

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

Continuous and twice-daily cefoxitin dosing was used in a highly lethal model of acute peritonitis in mice using intraperitoneal (IP) Klebsiella pneumoniae (Kpn). The purpose was to use antibiotics to create a model of chronic infection. Male Balb/c mice (averaging 20 g body weight) were inoculated IP with 10(3) colony-forming units (CFU) Kpn serotype 2. Controls received subcutaneous saline either twice daily or continuously. Antibiotic groups received 300 mg/kg per day of cefoxitin either twice daily or continuously. Survival and daily weight losses were determined. Another group was inoculated with 10(3) Kpn given twice daily saline or cefoxitin and harvested at 24 hours. Leukocyte counts were performed on peritoneal exudate cells (PEC) and peripheral blood. Cultures determined Kpn counts in blood, lung, and PEC. By 24 hours, saline-treated animals had lost more weight than cefoxitin mice (1 g vs. 2 g, P < 0.05). Continuous cefoxitin showed significant advantage with 50 per cent mortality at 5 days. Kpn levels were not significantly altered by cefoxitin. Cefoxitin treatment extended chronicity by preventing weight loss and increasing survival in a highly lethal, monomicrobial peritonitis model. This model will allow future study of specific host defense mechanisms over a prolonged time period.

Topics: Animals; Anti-Bacterial Agents; Ascitic Fluid; Bacteremia; Cefoxitin; Chronic Disease; Colony Count, Microbial; Disease Models, Animal; Injections, Subcutaneous; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Lung; Male; Mice; Mice, Inbred BALB C; Neutrophils; Peritonitis; Random Allocation; Serotyping; Survival Rate; Weight Loss

Over a 1-month period, a total of 16 ceftriaxone- and cefoxitin-resistant Klebsiella pneumoniae isolates were isolated from 15 patients hospitalised at a burns intensive care unit (ICU). These isolates showed negative results for extended-spectrum beta-lactamase (ESBL) by the Vitek system and were highly resistant to ceftazidime, aztreonam and cefoxitin (minimum inhibitory concentrations > or =128 microg/mL). The bla(SHV-2a) and bla(DHA-1) genes were detected by polymerase chain reaction and sequence analysis. Pulsed-field gel electrophoresis profiles of the isolates were identical. AmpC disk tests for AmpC enzymes as well as double-disk tests and Clinical and Laboratory Standards Institute (CLSI) confirmatory disk tests for ESBLs yielded positive results for all the isolates. However, only three isolates (18.8%) were shown to produce ESBL by CLSI confirmatory tests using broth microdilution. We report the first outbreak of colonisations and infections due to K. pneumoniae isolates co-producing an SHV-2a ESBL and a DHA-1 AmpC beta-lactamase in a Korean hospital, which were suggested to represent a single clonal spread at a burns ICU. In addition, this report presents problems associated with ESBL detection using broth microdilution in isolates that co-produce an ESBL and an AmpC beta-lactamase.

Topics: Anti-Bacterial Agents; beta-Lactamases; Burn Units; Cefoxitin; Cephalosporin Resistance; Cephalosporins; Disease Outbreaks; Humans; Klebsiella Infections; Klebsiella pneumoniae; Korea; Microbial Sensitivity Tests; Polymerase Chain Reaction

Eleven genotypically related Klebsiella pneumoniae isolates were obtained from 11 patients. All isolates were resistant to third-generation cephalosporins due to the production of SHV-2a extended-spectrum beta-lactamase. Comparison of the outer membrane protein profiles revealed one isolate that lacked porins. This porin-deficient isolate was also resistant to cefoxitin (MIC 128 microg ml(-1)) and moxalactam (MIC 64 microg ml(-1)) and had elevated MIC of meropenem (2 microg ml(-1)) when compared to porin-expressing isolates (2-8, 4 and <0.06-0.125 microg ml(-1), respectively). Higher MICs, associated with loss of porins in outer membrane, were also observed for cefotaxime (4-8-fold), cefepime (>2-16-fold), ciprofloxacin (4-16-fold), imipenem and aztreonam (2-16-fold), but there was no significant difference among MICs of ceftazidime. The porin-deficient mutant was probably selected in vivo during ofloxacin therapy.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; beta-Lactamases; Cefoxitin; Cephalosporin Resistance; Electrophoresis, Polyacrylamide Gel; Female; Genotype; Humans; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests

A strain of Klebsiella pneumoniae resistant to cefoxitin and oxyimino-cephalosporins, but susceptible to cefepime, was isolated from an adult patient hospitalised in Taichung, Taiwan. Isoelectric focusing revealed three beta-lactamases with isoelectric points of 5.4, 8.2 and 7.9, respectively. Following PCR with plasmid DNA templates and gene sequencing, these enzymes were shown to correspond to TEM-1, SHV-5 and a novel DHA-1-like enzyme (designated DHA-3). The bla genes for TEM-1 and SHV-5 were transferable, but the bla(DHA-3) gene was non-self-transferable in conjugation experiments. All three bla genes were successfully introduced by electrotransformation into an Escherichia coli recipient (DH5alpha), resulting in a similar resistance profile to that observed in the original donor strain. Other K. pneumoniae strains producing DHA-1-like enzymes have been identified previously in Taiwan, and this report suggests that DHA-type beta-lactamases are continuing to emerge in this country.

Topics: Adult; Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Cephalosporinase; Conjugation, Genetic; Drug Resistance, Bacterial; Escherichia coli; Gene Transfer, Horizontal; Genes, Bacterial; Humans; Isoelectric Point; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA; Taiwan

Detection of plasmid-mediated (P-M) AmpC beta-lactamase-producing isolates is considered critical for epidemiologic studies and hospital infection control, but the documents of the Clinical and Laboratory Standards Institute do not contain any recommendation for the phenotypic detection. In this study, phenotypic detection methods, cefoxitin-Hodge test and induction test, were evaluated using cefoxitin-resistant Escherichia coli and Klebsiella pneumoniae isolates. The cefoxitin-Hodge test detected all bla(CMY-10), and 97.4% of bla(CMY-2) allele-positive isolates, but only 57.3% of bla(DHA-1) allele-positive isolates. Induction test with an aztreonam and an amoxicillin-clavulanic acid disk was more sensitive than with cefoxitin disk, which detected 86.6% of bla(DHA-1) allele-positive isolates. These phenotypic tests should be useful to screen P-M AmpC beta-lactamase-producing E. coli and K. pneumoniae isolates.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefoxitin; Enzyme Induction; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Korea; Microbial Sensitivity Tests; Plasmids

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

Two hundred ninety isolates of Escherichia coli were investigated for the production of extended-spectrum beta-lactamases (ESBLs). Fourteen (4.8%) of the 290 strains were found to produce ESBLs. Each of the 14 strains produced one or two ESBLs, as follows: 10 strains produced TEM-52, 1 strain produced SHV-2a, 1 strain produced SHV-12, 1 strain produced a CMY-1-like enzyme, and 1 strain expressed SHV-2a and a CMY-1-like enzyme. Another two strains for which the MICs of ceftazidime and cefoxitin were high, were probable AmpC enzyme hyperproducers. Because of the high prevalence of TEM-52 in E. coli isolates, we further investigated the TEM-type ESBLs produced by Klebsiella pneumoniae in order to observe the distribution of TEM-52 enzymes among Enterobacteriaceae in Korea. All TEM enzymes produced by 12 strains of K. pneumoniae were identified as TEM-52. To evaluate the genetic relatedness among the organisms, ribotyping of TEM-52-producing E. coli and K. pneumoniae was performed. The ribotyping profiles of the organisms showed similar but clearly different patterns. In conclusion, TEM-52 is the most prevalent TEM-type ESBL in Korea.

Topics: Bacterial Proteins; beta-Lactamases; Cefoxitin; Ceftazidime; Cephalosporins; Conjugation, Genetic; Escherichia coli; Escherichia coli Infections; Hospitals, University; Humans; Klebsiella Infections; Klebsiella pneumoniae; Korea; Microbial Sensitivity Tests; Point Mutation; Polymerase Chain Reaction

Fifteen isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamases (ESBLs) isolated during a nosocomial outbreak were studied. The strains belonged to the same clonal type, as shown by pulsed-field gel electrophoretic analysis of chromosomal DNA. All the isolates were resistant to extended-spectrum cephalosporins, aztreonam, gentamicin, and fluoroquinolones and were susceptible to carbapenems, tobramycin, netilmicin, and amikacin. None of the isolates expressed the OmpK36 porin. Eight isolates, for which the MICs of cefoxitin were > or = 64 micrograms/ml, showed a diminished level or no expression of a 35-kDa porin. The MICs of meropenem, cefotaxime, and cefpirome were three to eight times higher for porin-deficient isolates than for isolates expressing the 35-kDa porin, but the MICs of imipenem increased two times for porin-deficient isolates compared to those for isolates expressing the porin. This MIC increase reverted to a level similar to that for the parental strain when porin-deficient isolates were transformed with the gene coding for the K. pneumoniae porin OmpK36. It is concluded that the high level of resistance to cefoxitin and the increase in the MICs of meropenem, cefotaxime, and cefpirome for the ESBL-producing K. pneumoniae isolates studied are associated with porin deficiency.

Topics: Bacterial Typing Techniques; beta-Lactamases; Carbapenems; Cefoxitin; Cephalosporins; Cephamycins; Cross Infection; Disease Outbreaks; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Porins; Spain

During a 3-month period, six Klebsiella pneumoniae isolates resistant to cefoxitin and penicillin-inhibitor combinations were derived from patients in the intensive care unit of a hospital in Athens, Greece. Enterobacterial repetitive intergenic consensus PCR and pulsed-field gel electrophoresis provided evidence of the clonal origin of the isolates. Conventional techniques and ribotyping were inadequate in proving that the isolates were related. Resistance was due to a plasmidic class C beta-lactamase.

Topics: Bacterial Typing Techniques; beta-Lactamases; Cefoxitin; Cephalosporin Resistance; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Greece; Hospitals, General; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Polymerase Chain Reaction; R Factors

Most of the open pelvic fractures are associated with skin wounds of varying anatomy. Injuries of the pelvis, which only momentarily communicate with the exterior or into a hollow organ are often difficult to diagnose. We managed a patient with an occult open displaced fracture of the public rami that had probably torn the hip capsule and was not recognised on admission as the open wound was in the vaginal wall. It subsequently resulted in septic arthritis of the ipsilateral hip joint. Vaginal and rectal examination in grossly displaced pelvic fractures should be done to diagnose at an early stage any occult open wound which may pose high risk of contamination of the fracture site.

Topics: Adult; Amikacin; Arthritis, Infectious; Cefoxitin; Drug Therapy, Combination; Female; Fractures, Open; Hip Joint; Humans; Klebsiella Infections; Pelvic Bones; Pseudomonas Infections

A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Ampicillin; Animals; Bacteremia; Cefoxitin; Drug Therapy, Combination; Granulocyte-Macrophage Colony-Stimulating Factor; Klebsiella Infections; Mice; Sulbactam; Surgical Wound Infection; Tumor Necrosis Factor-alpha

Clinical isolates identified as Klebsiella pneumoniae by the Vitek, Enterotube II, and API 20E systems were recovered from a patient undergoing therapy with imipenem/cilastatin. These isolates were resistant to multiple beta-lactam agents, and some were even resistant to imipenem. Analysis revealed a Bush group 1 beta-lactamase, and imipenem resistance corresponded to the loss of outer-membrane proteins in strains expressing high levels of this beta-lactamase. Further characterization efforts yielded abnormal but positive results of tests for ornithine decarboxylase production and motility, and chromosomal homology to an Enterobacter cloacae ampR, ampC probe was detected. These results suggested that the organisms were actually of an Enterobacter species, perhaps Enterobacter aerogenes. Cefoxitin resistance may be a useful marker for preventing this misidentification in the future; misidentification of such organisms poses a hazard, as it may lead to inappropriate beta-lactam therapy for infections caused by organisms that have the potential for resistance due to inducible group 1 cephalosporinases.

Topics: Aged; Cefoxitin; Cilastatin; Diagnosis, Differential; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male

An experimental Klebsiella pneumoniae pneumonia in rats was used to study the effect of protein binding of cefoxitin and cefazolin on their therapeutic activity. Both cephalosporins were similar with respect to their antimicrobial activity against the K. pneumoniae in vitro, but they differed in their degree of protein binding, being 34% for cefoxitin and 89 to 93% for cefazolin in uninfected rats and 24 and 71 to 83%, respectively, in infected rats. Various doses of these agents were administered by continuous infusion, which started 5 h after bacterial inoculation and continued for 65 h. Antimicrobial response was evaluated with respect to the numbers of bacteria recovered from lung and blood at the end of treatment. An inhibitory effect of protein binding on the in vivo antimicrobial activity was demonstrated. Cefoxitin was therapeutically effective at a constant plasma level that reached the MIC. To obtain a similar effect with cefazolin the plasma level of that drug had to be increased to a concentration more than three times the MIC.

Topics: Animals; Blood Proteins; Cefazolin; Cefoxitin; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Protein Binding; Rats; Time Factors

Cefoxitin sodium, a new cephamycin antibiotic, is active against many aerobic and anaerobic bacteria. Four patients with infections of the head and neck (otitis externa with cellulitis, parotiditis, tracheitis, and facial cellulitis), who had failed to respond to initial antibiotic regimens, responded satisfactorily to cefoxitin therapy. No adverse effects were noted in any of these patients. Results of this report suggest cefoxitin is a safe and well-tolerated antibiotic that is efficacious in the treatment of head and neck bacterial infections that are sensitive to this drug.

Topics: Adult; Aged; Cefoxitin; Cellulitis; Enterobacter; Female; Humans; Klebsiella; Klebsiella Infections; Male; Middle Aged; Otitis Externa; Sinusitis

Topics: Aged; Cefoxitin; Cephalosporins; Cross Infection; Drug Evaluation; Drug Resistance, Microbial; England; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; London; Male; Urinary Tract Infections

Topics: Bacterial Infections; Carbenicillin; Cefamandole; Cefazolin; Cefoxitin; Cephalosporins; Dose-Response Relationship, Drug; Escherichia coli Infections; Humans; Klebsiella Infections; Penicillins; Ticarcillin