Clindamycin suppresses endotoxin released by ceftazidime-treated Escherichia coli O55:B5 and subsequent production of tumor necrosis factor alpha and interleukin-1 beta.
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Treatment of septicemia caused by Escherichia coli with ceftazidime (CAZ) may be associated with the development of septic shock due to the release of bacterial lipopolysaccharide. We examined the suppressive effect of clindamycin (CLDM) on CAZ-induced release of endotoxin by cultured E. coli and the subsequent production of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-1 beta [IL-1 beta]). E. coli ATCC 12014 was incubated in inactivated horse serum with or without CLDM for 1, 4, or 18 h, followed by the addition of CAZ and collection of the culture supernatant at 0, 1, and 2 h. The concentration of endotoxin in each sample was measured by a chromogenic Limulus test. Another portion of the culture supernatant was added to THP-1 cell culture and incubated for 4 h, and the concentrations of TNF-alpha and IL-1 beta in the supernatant were measured by an enzyme-linked immunosorbent assay. In the control group (no CLDM), CAZ administration resulted in significant increases in endotoxin, TNF-alpha, and IL-1 beta concentrations. Pretreatment of E. coli with CLDM for 4 or 18 h before the addition of CAZ significantly suppressed the concentrations of endotoxin, TNF-alpha, and IL-1 beta in a time-dependent manner. In addition, CAZ treatment transformed E. coli from rodshaped bacteria to filament-like structures, as determined by electron microscopy, while pretreatment with CLDM prevented these morphological changes. Our in vitro studies showed that CAZ-induced release of large quantities of endotoxin by E. coli could be suppressed by prior administration of CLDM. (+info)
Molecular basis of AmpC hyperproduction in clinical isolates of Escherichia coli.
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DNA sequencing data showed that five clinical isolates of Escherichia coli with reduced susceptibility to ceftazidime, ceftriaxone, and cefotaxime contain an ampC gene that is preceded by a strong promoter. Transcription from the strong promoter was 8- to 18-fold higher than that from the promoter from a susceptible isolate. RNA studies showed that mRNA stability does not play a role in the control of AmpC synthesis. (+info)
Laboratory mutants of OXA-10 beta-lactamase giving ceftazidime resistance in Pseudomonas aeruginosa.
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Several extended-spectrum beta-lactamases (ESBLs) belonging to molecular Class D have been described from Pseudomonas aeruginosa isolates collected in Turkey. Four of these, OXA-11, -14, -16 and -17, are derivatives of OXA-10 beta-lactamase. We tried to select similar mutants in vitro from OXA-10-producing transconjugants of P. aeruginosa, using a multistep method on ceftazidime-containing agars. Forty-four such mutants were obtained; all had increased resistance to ceftriaxone, cefsulodin, cefepime, cefpirome, latamoxef, aztreonam and, especially, ceftazidime whereas MICs of piperacillin, carbenicillin, cefotaxime, cefoperazone and carbapenems were little altered. Genes related to blaOXA-10 were sequenced from five mutants. One mutant enzyme had aspartate instead of glycine at position 157, and corresponded exactly to natural OXA-14 beta-lactamase. Another mutant strain appeared to have both OXA-14 and a new pI 6.2 enzyme, designated OXA-M102, with serine instead of alanine at position 124 and aspartate instead of glycine at position 157. This latter variant resembled natural OXA-16 enzyme, which has threonine at position 124 and aspartate at position 157. The remaining three mutant enzymes differed from any so far found in wild-type isolates. Two had leucine replacing tryptophan at position 154 (this enzyme was named OXA-M101) while the third (OXA-M103) had a pI of 7.6, and had lysine instead of asparagine at position 143. A different mutation at this position was previously found in OXA-11, a wild-type OXA-10 mutant. Thus, some of the ESBL mutants selected (OXA-14 and OXA-M102) correspond exactly or almost exactly to ESBLs found in wild-types, whereas others (OXA-M101 and OXA-M103) were totally new. (+info)
Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin for the treatment of patients with nosocomial lower respiratory tract infection. Piperacillin/tazobactam Nosocomial Pneumonia Study Group.
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An open-label, randomized, comparative, multi-centre study was conducted at 25 centres in the USA and Canada to compare the safety and efficacy of piperacillin/tazobactam plus tobramycin with ceftazidime plus tobramycin in patients with lower respiratory tract infections. Piperacillin/tazobactam (3 g/375 mg) every 4 h or ceftazidime (2 g) every 8 h were administered i.v. for a minimum of 5 days. Tobramycin (5 mg/kg/day) given in divided doses every 8 h was administered to all patients. Patients with Pseudomonas aeruginosa isolated from respiratory secretions at baseline were to continue tobramycin for the duration of the study. Tobramycin could be discontinued in other patients after the baseline culture results were known. A total of 300 patients was randomized, 155 into the piperacillin/tazobactam group and 145 into the ceftazidime group. Of these, 136 patients (78 in the piperacillin/tazobactam group and 58 in the ceftazidime group) were considered clinically evaluable. Both groups were comparable for age, sex, duration of treatment and other demographic features. The clinical success rate in evaluable patients was significantly greater (P = 0.006) in the piperacillin/tazobactam treatment group (58/78; 74%) than in the ceftazidime group (29/58; 50%). Eradication of the baseline pathogen was significantly greater (P = 0.003) in the piperacillin/tazobactam group (66%) than in the ceftazidime group (38%). The clinical and bacteriological responses of those patients with nosocomial pneumonia were similar to the overall results. Twelve (7.7%) piperacillin/tazobactam-treated patients and 24 (17%) ceftazidime-treated patients died during the study (P = 0.03). Seven of the 24 deaths in the ceftazidime treatment group but only one of the 12 deaths in the piperacillin/tazobactam treatment group were directly related to failure to control infection. The majority of adverse events were thought by the investigator to be attributable to the patients' underlying disease and not drug related. In this study, piperacillin/tazobactam plus tobramycin was shown to be more effective and as safe as ceftazidime plus tobramycin in the treatment of patients with nosocomial LRTI. (+info)
In-vitro susceptibility of 1982 respiratory tract pathogens and 1921 urinary tract pathogens against 19 antimicrobial agents: a Canadian multicentre study. Canadian Antimicrobial Study Group.
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A total of 3903 pathogens from 48 Canadian medical centres were tested against 19 antimicrobial agents. Five agents showed activity against > or = 90% of all 1982 respiratory tract pathogens tested (ciprofloxacin, 90%; cefoperazone, 91%; ticarcillin/clavulanate, 92%; ceftazidime and imipenem, 93% each). Nine agents had > or = 90% activity against Enterobacteriaceae from respiratory tract infection (cefotaxime and ticarcillin/clavulanate, 90% each; aztreonam, ceftizoxime and ceftriaxone, 91% each; ceftazidime, 93%; ciprofloxacin, 97%; imipenem and netilmicin, 98% each). Similarly, five agents had activity against > or = 90% of all 1921 urinary tract pathogens tested (ciprofloxacin and ticarcillin/clavulanate, 90% each; cefoperazone and netilmicin, 91% each; imipenem, 99%). Nine agents had > or = 95% activity against Enterobacteriaceae from urinary tract infection (ciprofloxacin, 95%; cefotetan, 97%; aztreonam, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone and netilmicin, 98% each; imipenem, 99%). Seventeen agents had activity against > or = 95% of Staphylococcus aureus strains. Susceptibility of Pseudomonas aeruginosa isolates ranged from 2% to 91%. (+info)
Antibiotic dosing issues in lower respiratory tract infection: population-derived area under inhibitory curve is predictive of efficacy.
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Several lower respiratory tract infection (LRTI) trials have documented a correlation between clinical response and area under the inhibitory curve (24 h AUC/MIC; AUIC). The AUIC values in these studies were based on measured MICs and measured serum concentrations. This study evaluates AUIC estimates made using population pharmacokinetic parameters, and MICs from an automated microbiological susceptibility testing system. A computer database review over 2 years yielded 81 patients at Millard Fillmore Hospital with a culture-documented gram-negative LRTI who had been treated with piperacillin and an aminoglycoside, ceftazidime, ciprofloxacin or imipenem. Their AUIC values were estimated using renal function, drug dosages and MIC values. Outcome groups (clinical and microbiological cures and failures) were related to the AUIC values using Kruskal-Wallis ANOVA, linear regression and classification and regression tree (CART) analysis. A significant breakpoint for clinical cures was an AUIC value at least 72 SIT(-1) x 24 h (inverse serum inhibitory titre integrated over time). All antibiotics performed significantly better above this value than below it. Clinical cure was well described by a Hill-type equation. Within the piperacillin/aminoglycoside regimen, most of the activity came from the piperacillin, which had a higher overall AUIC value than the aminoglycoside. AUIC estimations based upon MIC values derived from the automated susceptibility testing method differed from NCCLS breakpoint data and from tube dilution derived values in this hospital by as much as three tube dilutions. These automated methods probably overestimated the MIC values of extremely susceptible organisms. The lack of precise MIC estimates in automated clinical microbiology methods impairs the use of AUIC to prospectively optimize microbiological outcome. Even ignoring this limitation and using the values as they are reported, the results of this analysis suggest that AUIC targets between 72 and 275 SIT(-1) x 24 h are useful in predicting clinical outcome. (+info)
A resuscitated case from asphyxia by large bronchial cast.
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A 62-year-old woman with bronchiectasis suffered from asphyxia due to a large bronchial cast that obstructed the bronchial tree. Immediate bronchoscopic suction of a bronchial cast of 17 cm in length through the intubated tube relieved the patients without any complications. Large bronchial casts appear to be rare in this century but it should be considered in patients with acute exacerbation of excessive sputa not only in patients with asthma or allergy but also in patients with respiratory tract infection. (+info)
Survey of extended-spectrum beta-lactamases in clinical isolates of Escherichia coli and Klebsiella pneumoniae: prevalence of TEM-52 in Korea.
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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. (+info)