Clindamycin plus gentamicin as expectant therapy for presumed mixed infections.
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The prevalence of obligate anaerobes was studied prospectively in 60 patients with severe sepsis of intra-abdominal, soft tissue, female genital or oropulmonary origin. In addition, the efficacy of clindamycin (for anaerobes) plus gentamicin (for aerobic bacteria, especially coliforms) as initial empiric therapy in these patients was evaluated. Among 54 patients with cultural proof of infection, anaerobic pathogens were recovered from 52%. Nineteen patients had bacteremia; Bacteroides fragilis and Klebsiella pneumoniae were the most prevalent pathogens, being isolated in five patients each. Infection was eradicated in 56 of the 60 patients (93%). Mortality related to sepsis was 7% in the entire group, 16% in patients with bacteremia and 2% in patients without bacteremia. Eighty-five percent of aerobic isolates tested were susceptible in vitro to either gentamicin or clindamycin; 97% of anaerobic isolates were inhibited by 5 mug/ml of clindamycin. (+info)
Clindamycin suppresses endotoxin released by ceftazidime-treated Escherichia coli O55:B5 and subsequent production of tumor necrosis factor alpha and interleukin-1 beta.
(2/791)
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)
Antibiotic penetrance of ascitic fluid in dogs.
(3/791)
Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak x100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients. (+info)
A new resistance gene, linB, conferring resistance to lincosamides by nucleotidylation in Enterococcus faecium HM1025.
(4/791)
Resistance to lincomycin and clindamycin in the clinical isolate Enterococcus faecium HM1025 is due to a ribosomal methylase encoded by an ermAM-like gene and the plasmid-mediated inactivation of these antibiotics. We have cloned and determined the nucleotide sequence of the gene responsible for the inactivation of lincosamides, linB. This gene encodes a 267-amino-acid lincosamide nucleotidyltransferase. The enzyme catalyzes 3(5'-adenylation) (the adenylation of the hydroxyl group in position 3 of the molecules) of lincomycin and clindamycin. Expression of linB was observed in both Escherichia coli and Staphylococcus aureus. The deduced amino acid sequence of the enzyme did not display any significant homology with staphylococcal nucleotidyltransferases encoded by linA and linA' genes. Sequences homologous to linB were found in 14 other clinical isolates of E. faecium, indicating the spread of the resistance trait in this species. (+info)
Antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from children in Lesotho.
(5/791)
Villages associated with the Lesotho Highlands Development Agency were randomized with a bias in favour of larger villages, and children < 5 years of age from cluster-randomized households in these villages were chosen for the assessment of antibiotic resistance in pneumococci. Children of the same age group attending clinics in the capital, Maseru, were selected for comparison. Nasopharyngeal cultures of Streptococcus pneumoniae from both groups of children were examined for antibiotic resistance and a questionnaire was used to assess risk factors for the acquisition of resistant strains. Carriage of penicillin- and tetracycline-resistant pneumococci was significantly higher among 196 Maseru children compared with 324 rural children (P < 0.05 and P = 0.01, respectively). Maseru children tended to visit clinics at an earlier age compared with their rural counterparts. The rural children were less exposed to antibiotics (P < 0.01), were less frequently hospitalized (P < 0.001), and rarely attended day care centres (P < 0.001). The very low incidence of antibiotic resistance in rural Lesotho and the higher incidence in Maseru are in stark contrast with the much higher frequencies found in the Republic of South Africa, many European countries, and the USA. (+info)
In-vitro susceptibilities of species of the Bacteroides fragilis group to newer beta-lactam agents.
(6/791)
The in-vitro activities of imipenem and four beta-lactam-beta-lactamase inhibitor combinations were tested against 816 strains of the Bacteroides fragilis group, and compared with other anti-anaerobic agents. None of the strains was resistant to metronidazole, and only one was resistant to chloramphenicol. Mezlocillin and piperacillin were moderately active, while clindamycin was the least active. Rates of resistance varied between various species. The new beta-lactam agents tested showed excellent activity; piperacillin-tazobactam and imipenem were the most active. The emergence of strains that are resistant to these agents, observed in this study, suggests there is a need to perform periodic antimicrobial susceptibility tests. (+info)
Distribution of mefE and ermB genes in macrolide-resistant strains of Streptococcus pneumoniae and their variable susceptibility to various antibiotics.
(7/791)
From February to October 1995, 62 erythromycin-resistant strains of Streptococcus pneumoniae isolated at Yamanashi Red Cross Hospital were tested to determine their susceptibility to various macrolides, subjected to resistance induction tests by the disc diffusion method and analysed for genes encoding resistance to macrolides (ermB and mefE). On the basis of resistance induction testing, the isolates were classified as having either inducible (59.7%) or non-inducible (40.3%) macrolide resistance. The ermB gene was always detected in resistance-inducible type isolates, either alone or in combination with mefE. The mefE gene alone was found only in non-inducible type isolates. Isolates with non-inducible resistance (those with only the mefE gene) had an intermediate level of resistance to 14-membered macrolides, and were susceptible to rokitamycin, a 16-membered macrolide. According to NCCLS guidelines, 9.6% of S. pneumoniae strains were judged to be susceptible to penicillin, 62.9% of reduced susceptibility and 27.4% penicillin resistant. No correlation was detected between the presence of particular macrolide-resistance genes (ermB, ermB + mefE, or mefE) and resistance to penicillin G. (+info)
Further evolution of a strain of Staphylococcus aureus in vivo: evidence for significant inactivation of flucloxacillin by penicillinase.
(8/791)
A strain of Staphylococcus aureus (no. FAR4) has been isolated at intervals, for 32 months, from the sputum of a patient with cystic fibrosis of the lung. Changes in the properties of isolates of this strain over the first 18 months have been reported previously (Lacey et al., 1973 and 1974). During the last 14 months (May 1973 to July 1974), further evolution has occurred to produce a total of 31 distinct phenotypes. Recent changes are as follows. 1. The ability of isolates to produce penicillinase in vitro was closely correlated with flucloxacillin therapy. Inactivation of flucloxacillin by penicillinase was demonstrated by diffusion testing (but not MIC determination) in vitro and may have occurred to a significant extent in vivo. 2. Lincomycin-resistant mutants slowly disappeared from the sputum after the termination of clindamycin therapy. 3. All of the recent isolates were resistant to erythromycin, possibly because of the linkage of the genes coding for erythromycin resistance with those coding for the production of delta-haemolysin; delta-haemolysin may be an important "virulence factor". (+info)