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[The antibacterial efficacy of cefaclor in routine testing of clinical material from two Berlin hospitals (author's transl)].

The agar diffusion method was used to test the antibacterial efficacy of cefaclor against bacterial strains isolated routinely from patients in two hospitals in Berlin. A comparison was made with the efficacy of oxacillin, azlocillin, amikacin, gentamicin, ampicillin, co-trimoxazole, tetracycline, penicillin, cefazolin, nalidixic acid and nitrofurantoin. A total of 1235 strains of Staphylococcus aureus, enterococci, Escherichia coli, Klebsiella, Enterobacter, Proteus species, Citrobacter and Pseudomonas aeruginosa were tested. Cefaclor was superior to the other substances in its activity against E. coli, Klebsiellae, and Proteus mirabilis. Co-trimoxazole and tetracycline, on the other hand, proved more effective against indole-positive Proteus species and Citrobacter. Tetracycline was also more effective against Enterobacter. Ampicillin was the most effective agent against enterococci, and oxacillin the most effective against S. aureus. Cefaclor showed good antibacterial activity against strains which were resistant to the orally administrable agents ampicillin, tetracycline and co-trimoxazole.

Bacteria↗

The antimicrobial activity of cefotaxime: comparative multinational hospital isolate surveys covering 15 years.

The "third-generation" cephalosporins (3GC) have emerged as one of the most significant therapeutic entities in the last 15 years. These 3GC compounds (using cefotaxime as a model) have generally maintained their potency and spectrum of activity against important pathogens. However, the continuing popularity of this class associated with local, regional, or national-level use or abuse has led to efficacy reduction against some organism populations associated with selection of Class I cephalosporinase, stably derepressed mutants predominantly among Citrobacter and Enterobacter spp.; emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (usually Klebsiella spp.), as well as some isolates mimicking Class I-type resistance patterns; and lastly, altered PBP-mediated resistances among pneumococci, Haemophilus influenzae and pathogenic Neisseria spp. Some of these resistance patterns had been present prior to the clinical introduction of 3GCs and have only significantly threatened their use in the last 5 years. Prudent application of these 3GC drugs should be the goal for this decade as follows: 1) use as monotherapy at appropriate doses and frequencies only for organisms with low potential for mutational events; 2) use combination therapy routinely for organisms such as Citrobacter, Enterobacter, some indole-positive protease and Pseudomonas aeruginosa, to minimize emerging resistance clones; 3) use conservatively in high risk patients to minimize "super-colonization" by emerging problem bacteria (e.g. vancomycin-resistant enterococci, Xanthomonas maltophilia etc.); 4) use only those agents among 3GCs that have documented safety, broad clinical applications to all age groups, acceptable pharmacokinetic features and clear cost-saving potential; and 5) use in prophylaxis (surgical procedure, selective decontamination), should be focused toward single-dose or short-course regimens to reduce total hospital-wide exposure to broad-spectrum beta-lactam drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime↗

In vitro activity of Ro 09-1428 compared to other cephalosporins.

The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gram-negative organisms. Ro 09-1428 inhibited group A streptococci at less than or equal to 0.12 micrograms/ml, and group B, C and G streptococci and Streptococcus pneumoniae at 0.5 micrograms/ml, whereas for Staphylococcus aureus Ro 09-1428 had MICs of 8-16 micrograms/ml similar to ceftazidime and E-1040. Against Pseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at less than or equal to 0.12-2 micrograms/ml, and inhibited ceftazidime-resistant isolates. The majority of Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella and Shigella were inhibited by less than or equal to 0.5 micrograms/ml as with the other cephalosporins. For most Citrobacter freundii and Enterobacter cloacae Ro 09-1428 had higher MICs of 4-16 micrograms/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci and Listeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2, Staphylococcus aureus PC-1, Moraxella catarrhalis Bro-1, Enterobacter P-99, Pseudomonas aeruginosa Sabath-Abraham or Klebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH.

Cephalosporins↗

Comparison of three methods for identification of Enterobacteriaceae.

This study compares the ability of three commercial overnight methods, API 20E, Minitek and Enteric-Tek, to accurately and completely identify 368 clinically isolated Enterobacteriaceae without supplemental tests. Organisms included Escherichia coli (54 strains), Shigella spp. (7), Edwardsiella tarda (1), Salmonella enteritidis (10), Citrobacter spp. (30), Klebsiella spp. (55), Enterobacter spp. (68), Hafnia alvei (2), Serratia spp. (33), Proteus spp. (64), Morganella morganii (24), Providencia spp. (18), and Yersinia enterocolitica (2). Methods were those of the manufactures without supplemental tests. API 20E correctly identified 93.2% of strains to species and 3.3% to genus level only, with 3.0% as part of a spectrum of identifications, and 0.5% incorrect identifications. Minitek yielded 96.0% correct identifications to species and 0.5% to genus level only, with 2.5% spectrum identifications, and 1.0% incorrect identifications. Enteric-Tek correctly identified 97.0% of strains to species level with 3.0% spectrum identifications. API 20E identification of some Serratia and Citrobacter strains was to genus level only. Problem organisms for Minitek included Enterobacter agglomerans and Serratia marcescens. A comparison of these three commercial methods shows that all three have the ability to identify most clinically isolated Enterobacteriaceae without supplemental tests.

Bacteriological Techniques↗

Bacterial interference by anaerobic species isolated from human feces.

Eighty-four anaerobic fecal isolates obtained from five healthy volunteers were tested for their ability to inhibit in vitro growth of eight species of Enterobacteriaceae, four species of faculative gram-positive cocci, and Pseudomonas aeruginosa. Forty-nine of the 84 anaerobic isolates (58%) inhibited the growth of at least one indicator bacterium. Isolates of Bacteroides and Bifidobacterium spp. were most consistently inhibitory. Anaerobic cocci and clostridia were infrequently inhibitory; eubacteria showed no inhibitory activity. Serratia marcescens was the indicator most often inhibited; 54% of all anaerobic isolates tested, all of nine Bifidobacterium isolates and 33 of 43 Bacteroides isolates inhibited this organism. No anaerobes inhibited the growth of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter freundii, Citrobacter diversus or Streptococcus faecalis.

Adult↗

Occurrence of strains producing specific antibacterial inhibitory agents in five genera of Enterobacteriaceae.

Striking differences in the production of specific inhibitory agents affecting other strains of the same (or of related) species were found between genera of the family Enterobacteriaceae. We tested 50-163 strains each of the potentially pathogenic genera: Escherichia, Citrobacter, Enterobacter, Kluyvera, and Leclercia for their ability to produce bacteriophages, high-molecular-weight (HMW) and low-molecular-weight (LMW) bacteriocins and siderophores against the same sets of strains, using the cross-test method. The genus Escherichia differs substantially from all other Enterobacteriaceae, harboring a notable proportion of lysogenic (36.6%) and colicinogenic (13.9%) strains. Only 18.2% of the Citrobacter strains are lysogenic and only rarely are they colicinogenic, although in 7.3%, they produce phage tail-like bacteriocins. On the other hand, Kluyvera strains were only in 1.8% lysogenic, no colicinogenic strains were found, but in 7.3%, they produced siderophores causing zones of growth inhibition in agar cultures of strains of the same genus. In Leclercia, 10.0% of the strains were lysogenic, 2.0% produced HMW bacteriocins, no colicinogenic strains were found and 2.0% produced siderophores. Enterobacter has shown 23.1% of strains producing siderophores, whereas merely 7.7% were lysogenic, 1.9% colicinogenic and 3.8% formed phage tail-like bacteriocins. HMW bacteriocins of Enterobacter strains disposed of an unusually wide spectrum of activity. The siderophore activity spectrum was rather wide in any genus, but the siderophores were usually not produced by strains producing phages or colicins.

Anti-Bacterial Agents↗

Utility of serial rectal swab cultures for detection of ceftazidime- and imipenem-resistant gram-negative bacilli from patients in the intensive care unit.

Forty-four patients receiving intensive care were studied prospectively to assess the utility of serial rectal swab cultures and clinical correlates of resistance for Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., Morganella morganii, and Serratia marcescens strains resistant to ceftazidime or imipenem. Strains of Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., or Morganella morganii were found in 26 of 44 (59%) patients: 17 (65%) in clinical sites (11 with concomitant rectal isolates) and nine (35%) in a rectal site only. Of 49 total isolates, 13 (26.5%) were resistant: 10 (20.4%) to ceftazidime and three (6.1%) to imipenem. Surveillance rectal swabs from 27 patients without a clinical isolate identified two patients with resistant organisms (15% of all resistant isolates). The majority of resistance to ceftazidime or imipenem among Pseudomonas or Enterobacter can be detected by the use of clinical specimens alone.

Adult↗

Epidemiological role of arthropods detectable in health facilities.

A total of 161 arthropod specimens were collected from 55 sites in a health care facility during July and September 1990. Of the 116 bacterial isolates obtained from their body surfaces 6% were from parasites (mosquitoes), 59% from eusynanthropic arthropods (Tenebrionid beetles, flies, German cockroaches, wasps), 16% from hemisynanthropic arthropods (ants, spiders) and 19% from occasionally encountered insects (non-biting midges, moths, beetles). Most (88%) of the isolated bacteria were Gram-negative rods of the species E. coli, Enterobacter, Klebsiella, Citrobacter, Proteus, Serratia, Pseudomonas and Acinetobacter. Gram-positive cocci accounted for 13% of isolates and were primarily represented by coagulase-negative staphylococci. The highest isolation rates were from body surfaces of flies, German cockroaches, non-biting midges (Chironomids) and Tenebrionid beetles. About one third of all isolates were resistant to more than three antimicrobials using a standard disc diffusion assay. The presence of multiple resistance to antibiotics was observed in two thirds of Enterobacter isolates, namely those of Enterobacter cloacae from the body surface of Germany cockroaches, in 13% of Citrobacter spp and in 8% of Klebsiella spp as well as Acinetobacter calcoaceticus strains. Strains of Morganella and Hafnia species were very infrequent but all of them shared resistance to the antibiotics tested. In contrast, strains of Serratia spp were relatively antibiotic-sensitive. The group of isolated Gram-positive organisms was represented by two strains of Staphylococcus hominis and one strain of Enterococcus sp, all of them were multiply-resistant to antimicrobials.

Animals↗

Antimicrobial activity and beta-lactamase stability of SK&F 88070 compared with other agents.

The in vitro activity and beta-lactamase stability of SK&F 88070 (7-[[2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[ [1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio]methyl]-3- cephem-4-carboxylic acid) a new parenteral cephalosporin was investigated against 780 types of bacteria. SK&F 88070 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, Shigella species, Morganella morganii, and Citrobacter diversus at less than or equal to 0.5 micrograms/ml. Its activity against these species was similar to cefotaxime and moxalactam and superior to cefoperazone and piperacillin. It was less active than cefoperazone against Pseudomonas aeruginosa and less active than cefotaxime or cefoperazone against Staphylococcus aureus. SK&F 88070 inhibited hemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.12 micrograms/ml. Enterobacter species, Citrobacter freundii, and Serratia, which were resistant to cefotaxime and moxalactam were resistant to SK&F 88070. It was not hydrolyzed by plasmid beta-lactamases, but was hydrolyzed by the Proteus vulgaris type 1c enzyme. SK&F 88070 inhibited Richmond-Sykes type 1a beta-lactamases.

Anti-Bacterial Agents↗

In vitro activity of HRE 664, a penem antibiotic.

HRE 664, a new penem antibiotic, inhibited 90% of Escherichia coli, Klebsiella, Citrobacter diversus, Proteus mirabilis, Proteus vulgaris, Salmonella, Shigella, Providencia, Aeromonas, and Morganella at less than or equal to 2 micrograms/ml but was considerably less active than cefotaxime, ceftazidime, and imipenem. It did not inhibit Pseudomonas aeruginosa (MIC greater than 128 micrograms/ml). HRE 664 inhibited Enterobacter spp., Citrobacter freundii, and Serratia marcescens at 1-8 micrograms/ml, two- to fourfold higher MICs than imipenem. HRE 664 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 0.12 micrograms/ml, but methicillin-resistant S. aureus and S. epidermidis were resistant. Group A, C, and G streptococci and Streptococcus pneumoniae were inhibited by 0.06 micrograms/ml. Bacteroides and Clostridium species were inhibited by 0.25 micrograms/ml comparable to imipenem. HRE 664 was not hydrolyzed by beta-lactamases TEM-1, TEM-2, TEM-3, TEM-5, SHV-1, PSE-1, PSE-4, OXA-2, OXA-3, K-1, P99, Morganella, P. vulgaris, and S. aureus PC-1 but was hydrolyzed by the beta-lactamase of Xanthomonas maltophilia.

Amikacin↗

Taxonomic diversity of anaerobic glycerol dissimilation in the Enterobacteriaceae.

A total of 1,123 strains representing 128 taxa in the Enterobacteriaceae (named species or subspecies and genomic species) were screened for the presence of glycerol dehydrogenases and 1,3-propanediol dehydrogenase. Only eight taxa, Citrobacter freundii sensu stricto, C. youngae, C. braakii, C. werkmanii, Citrobacter genomospecies 10 and 11, Enterobacter gergoviae and Klebsiella pneumoniae subsp. pneumoniae could grow fermentatively on glycerol and possessed both glycerol dehydrogenase type I (induced by glycerol and dihydroxyacetone) and 1,3-propanediol dehydrogenase which are typical enzymes of the anaerobic glycerol dissimilation pathway. Six other species, C. koseri, E. aerogenes, E. intermedium, K. oxytoca, K. planticola and K. terrigena could not grow fermentatively on glycerol and possessed a glycerol dehydrogenase type I but no 1,3-propanediol dehydrogenase. Other glycerol dehydrogenases types were found: type II (induced by glycerol and hydroxyacetone), type III (induced by glycerol only) and type IV (induced by hydroxyacetone only). They were widely distributed among the Enterobacteriaceae. Classification and identification may take advantage of tests exploring the dissimilation of glycerol.

Enterobacteriaceae↗

Characterization of bacterial community associated to biofilms of corroded oil pipelines from the southeast of Mexico.

Microbial communities associated to biofilms promote corrosion of oil pipelines. The community structure of bacteria in the biofilm formed in oil pipelines is the basic knowledge to understand the complexity and mechanisms of metal corrosion. To assess bacterial diversity, biofilm samples were obtained from X52 steel coupons corroded after 40 days of exposure to normal operation and flow conditions. The biofilm samples were directly used to extract metagenomic DNA, which was used as template to amplify 16S ribosomal gene by PCR. The PCR products of 16S ribosomal gene were also employed as template for sulfate-reducing bacteria (SRB) specific nested-PCR and both PCR products were utilized for the construction of gene libraries. The V3 region of the 16S rRNA gene was also amplified to analyse the bacterial diversity by analysis of denaturing gradient gel electrophoresis (DGGE). Ribosomal library and DGGE profiles exhibited limited bacterial diversity, basically including Citrobacter spp., Enterobacter spp. and Halanaerobium spp. while Desulfovibrio alaskensis and a novel clade within the genus Desulfonatronovibrio were detected from the nested PCR library. The biofilm samples were also taken for the isolation of SRB. Desulfovibrio alaskensis and Desulfovibrio capillatus, as well as some strains related to Citrobacter were isolated. SRB consists in a very small proportion of the community and Desulfovibrio spp. were the relatively abundant groups among the SRB. This is the first study directly exploring bacterial diversity in corrosive biofilms associated to steel pipelines subjected to normal operation conditions.

Bacteria↗

Evaluation of antimicrobial activity of beta-lactam antibiotics by Etest against clinical isolates from 100 medical centers in Japan (2004).

This antimicrobial resistance surveillance study was performed in 100 medical centers. The susceptibility of 9347 strains including Escherichia coli (997 strains), Klebsiella spp. (997 strains), Enterobacter spp. (988 strains), Citrobacter spp. (834 strains), indole-positive Proteae spp. (855 strains), Serratia spp. (925 strains), Acinetobacter spp. (902 strains), Pseudomonas aeruginosa (996 strains), oxacillin-susceptible Staphylococcus aureus (992 strains), and coagulase-negative staphylococci (861 strains) to 7 beta-lactam antibiotics, cefepime, cefpirome, ceftazidime, cefoperazone/sulbactam, imipenem and piperacillin (for gram negatives), or oxacillin (for gram positives) was tested. No strain resistant to these beta-lactams except for ceftazidime was found in oxacillin-susceptible S. aureus and coagulase-negative staphylococci. E. coli (16.5%) clinical isolates were resistant to piperacillin, whereas 1.5% or less (cefpirome = 1.5%) was resistant to other beta-lactams. Klebsiella spp. strains were more susceptible to imipenem (99.7%), cefepime (98.4%), and cefpirome (97.3%). Isolates of Enterobacter spp., Citrobacter spp., indole-positive Proteae, and Serratia spp. were susceptible to imipenem, cefepime, and cefpirome, as well. Acinetobacter spp. strains were most susceptible to cefoperazone/sulbactam (0.8% resistance), imipenem (3.2%), ceftazidime (6.0%), and cefepime (7.0%) than other beta-lactam antibiotics tested. Isolates of P. aeruginosa were more susceptible to ceftazidime (9.9% resistance), cefoperazone/sulbactam (14.9%), and cefepime (11.2%) than piperacillin (15.5%), cefpirome (19.1%), and imipenem (19.3%). The percentage of imipenem-resistant P. aeruginosa is around 20% in clinical isolates in Japan.

Anti-Bacterial Agents↗

Antimicrobial activity of cefepime tested against ceftazidime-resistant Gram-negative clinical strains from North American Hospitals: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

To assess the effect of ceftazidime resistance on the activity of other antimicrobial agents, 3030 ceftazidime-resistant Gram-negative bacilli (GNB) isolates (of a total of 42061 GNB) were tested against a panel of more than 30 agents. Ceftazidime resistance was observed in 40.3% of Acinetobacter spp., 16.9% of Pseudomonas aeruginosa, and 5.7% of Enterobacteriaceae isolates. The highest rates of ceftazidime resistance among the enteric GNB were observed with Enterobacter spp. (20.9%) >Citrobacter spp. (15.3%) > indole-positive Proteae (10.1%). Overall, 90% of ceftazidime-resistant Enterobacteriaceae and 30% of ceftazidime-resistant P. aeruginosa remained susceptible to the "4th-generation" cephalosporin, cefepime. The activities (% susceptible) of other antimicrobials tested against ceftazidime-resistant Enterobacteriaceae and P. aeruginosa, respectively, were as follows: amikacin, 90% and 88%; ciprofloxacin, 63% and 46%; gentamicin, 59% and 67%, imipenem, 99% and 65%; levofloxacin, 69% and 44%; and piperacillin/tazobactam only 40% and 12%. Ceftazidime-resistant GNB exhibited high rates of resistance to other antimicrobials. Cefepime was very active against ceftazidime-resistant enteric GNB (AmpC enzyme producers), especially Enterobacter spp. (94.3% susceptible), Citrobacter spp. (96.7% susceptible), and indole-positive Proteae (89.6% susceptible), and showed activity similar to that of ceftazidime against all P. aeruginosa and Acinetobacter spp. isolated in North American medical centers. Continued resistances surveillance monitoring will be necessary to assess the effectiveness of widely used broad-spectrum antimicrobials as novel resistance mechanisms emerge.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of inducible AmpC beta-lactamase-producing Enterobacteriaceae from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme, Europe 1997-2000.

Among 11345 clinical isolates from 31 European centres in the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme (1997-2000), the potential AmpC-producing pathogens were Enterobacter spp. (904 cases), Citrobacter spp. (144) and Serratia marcescens (288). Resistance to ceftazidime or cefotaxime (11-34%) and piperacillin/tazobactam (12%) was observed, indicating stably derepressed expression of AmpC cephalosporinases. Meropenem (MIC(90), 0.25 mg/l; >99% susceptible) and imipenem (MIC(90), 2 mg/l; 98% susceptible) were active, even against these stably derepressed AmpC-producers: Enterobacter spp. (305 strains), Citrobacter spp. (29) and S. marcescens (35). The overall rank order of spectrum (% susceptible) versus the stably derepressed subset of isolates was: meropenem=imipenem (98%)>cefepime (89%)>gentamicin (73%)>ciprofloxacin (62%)>tobramycin (60%) >piperacillin/tazobactam (21%). We suggest increased attention in Europe to: (1) the recognition of these resistant phenotypes, (2) infection control practices, and (3) limiting the overuse of certain selecting extended-spectrum beta-lactam agents (e.g. ceftazidime).

Anti-Bacterial Agents↗

Variation in skin and environmental survival of hospital gentamicin-resistant enterobacteria.

During a period when 245 patients were infected by or harboured gentamicin-resistant enterobacteria, random sampling showed hand carriage in 33% of affected patients but in only 5% of attendant staff. Only klebsiellae were isolated from the latter. Recovery was commoner from the hands of bed-ridden patients or faecal carriers and significantly more frequent for klebsiellae (37%) and enterobacter (33%) than citrobacter (5.6%) and E. coli (5.0%). Similarly, survival on forearms of volunteers was much longer for klebsiellae and enterobacter than for citrobacter or E. coli (means respectively were 70, 45, 10 and 13 min), and on dry surfaces (means respectively were 28, 26, 3 and 7 h). Klebsiellae were isolated from 17 of the 56 dry environmental surfaces sampled. The presence of plasmid resistance determinants had no effect on survival times, either on the skin or following drying onto formica surfaces. On dry surfaces 9.5% of E. coli but only 1.3% of klebsiellae lost resistance to gentamicin. These findings accord well with recent experience in which gentamicin-resistant klebsiellae have been involved to a much greater extent than other resistant enterobacteria in hospital infection.

Cross Infection↗

Further observations on the serological response to experimental Salmonella typhimurium in chickens measured by ELISA.

An indirect ELISA developed for the serological detection of Salmonella typhimurium in chickens using lipopolysaccharide as detecting antigen has been evaluated further in experimental infections. Following oral infection of 24-week-old laying hens with an invasive strain of S. typhimurium, high titres of specific circulating IgG were induced which were maintained for 20 weeks. Similar IgG titres were found in egg yolk. When 4-day-old chickens were infected high antibody titres persisted for 45 weeks. Chickens inoculated orally or intramuscularly with different numbers of S. typhimurium organisms showed graded serum IgG responses to LPS. The IgG titres in experimentally infected in-bred lines of chickens which showed greater genetic resistance to salmonella infection were significantly lower than those found in more susceptible lines. Oral and intramuscular infection with 18 different types of enterobacteria, including avian pathogenic E. coli, Citrobacter spp., Klebsiella spp., Proteus spp. and citrobacter-like organisms possessing some salmonella LPS (none possessed the O-4 antigen) and flagella antigens, did not induce S. typhimurium LPS-specific IgG responses. Chickens infected orally with rough or non-flagellate mutants of S. typhimurium did not induce high titres of LPS or flagella-specific IgG respectively. Sera obtained from S. typhimurium-infected chickens showed much higher titres against S. typhimurium LPS than with those antigens from other serotypes, including S. enteritidis.

Animals↗

Serum bactericidal activity of trovafloxacin, in combination with cefepime or amikacin, in healthy volunteers.

OBJECTIVE: To investigate the phamacokinetics and serum bactericidal activities (SBAs) of trovafloxacin, cefepime and amikacin alone and trovafloxacin in combination with cefepime or amikacin, so that the most favorable combination with trovafloxacin can be determined. METHODS: In this open, randomized, crossover study, 12 healthy volunteers (six females, six males; mean age +/- SD, 25.1 +/- 2.6 years) received an infusion of either 300 mg of alatrovafloxacin or 2000 mg of cefepime or 6 mg/kg body weight amikacin alone, or 300 mg of alatrovafloxacin plus 2000 mg of cefepime or plus 6 mg/kg body weight amikacin. The SBAs against Pseudomonas aeruginosa, Staphylococcus aureus (11 strains each), Citrobacter freundii and Acinetobacter spp. (10 strains each) 1, 10 and 24 h after drug administration were measured by a standard microdilution method. Concentrations of trovafloxacin, cefepime and amikacin in serum and urine were analyzed before and up to 10 and 12 h, respectively, after drug infusion. RESULTS: Significant synergistic effects on SBA were observed with the combination of trovafloxacin and cefepime against P. aeruginosa, S. aureus and Acinetobacter spp. 1 h after drug administration, and against Citrobacter freundii 1, 10 and 24 h after drug administration. The combination of trovafloxacin and amikacin showed significant synergistic effects against P. aeruginosa, S. aureus and C. freundii 1 h after drug administration. The combination of trovafloxacin and cefepime was, in general, more active than the combination of trovafloxacin and amikacin. No significant differences in the serum concentrations of trovafloxacin were observed between single and combined administration. However, the maximal concentration of cefepime was significantly lower when it was used in combination with trovafloxacin. CONCLUSION: Our study suggests a favorable interaction between trovafloxacin and cefepime. This combination showed more synergistic bactericidal activity against most of the test strains compared to the combination of trovafloxacin and amikacin. However, for P. aeruginosa, the bactericidal activity of cepefime alone was higher than that of the combination with trovafloxacin.

Adult↗