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PubMed1992

Antimicrobial resistance: patterns and trends in the National University Hospital, Singapore (1989-1991).

The commonly isolated organisms, Staphylococcus aureus, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Acinetobacter species, Proteus species and Enterobacter species from clinical material other than blood, cerebrospinal fluid and stool, were analysed for their incidence and increasing trends of resistance to the commonly used antimicrobials. Staphylococcus aureus was tested against penicillin, methicillin, erythromycin, gentamicin and co-trimoxazole; Pseudomonas aeruginosa against amikacin, ceftazidime, gentamicin, piperacillin and cefsulodin; and gram negative bacilli against ampicillin, co-trimoxazole, cephalexin, cefuroxime, ceftriaxone, nalidixic acid and nitrofurantoin. Methicillin sensitive Staphylococcus aureus exhibited a high degree of resistance to penicillin only (83%), but methicillin resistant Staphylococcus aureus (34-46%) showed nearly 100% resistance to all drugs tested except for co-trimoxazole over the period of study. A high incidence of resistance was found among Klebsiella species, Enterobacter species, Acinetobacter species and Pseudomonas species. Increasing trends of resistance against cephalosporins were noticed with respect to Acinetobacter species, Klebsiella species and Enterobacter species for cefuroxime and ceftriaxone; Pseudomonas aeruginosa for ceftazidime and cefsulodin. The overall resistance of organisms is notably high. Methicillin-resistant S. aureus is endemic and accounts for about 39% of all S. aureus isolates. The typical nosocomial organisms like Acinetobacter species and Klebsiella species are increasingly developing resistance to useful drugs such as gentamicin, cephalexin and ceftriaxone.

Cephalosporins↗
PubMed1992

[Survey of bacterial resistance in Shanghai district].

The data on bacterial resistance monitoring of 5,457 clinical isolates in 1990 against 21 antimicrobial agents showed that most isolates were highly resistant to commonly used antimicrobial agents, such as penicillin, ampicillin, erythromycin, chloramphenicol, tetracycline and gentamicin, with a resistant rate of around 50% or more. Strains resistant to some newer agents, such as cefotaxime, ceftazidime, amikacin and norfloxacin, have appeared and are increasing in number. Multi-resistant strains, i.e. strains resistant to five more antimicrobial agents existed in various bacterial species. Vancomycin was the most active antibiotic against methicillin-resistant staphylococci and no resistant strains were found. Strains of Salmonella and Shigella spp. were still very sensitive to the antimicrobial agents tested, with a sensitive rate of more than 90%. 80% of 765 gentamicin-resistant strains of Enterobacteriaceae were still sensitive to amikacin.

Ampicillin Resistance↗
PubMed1992

Problems and dilemmas of antimicrobial resistance.

An important obstacle to the long-term efficacy of an antimicrobial agent is the appearance and spread of resistance to the agent. The fact that many antimicrobials are produced by microorganisms in nature may provide long-term selective pressure for the emergence of resistance in antibiotic-producing as well as -nonproducing organisms. Indeed, the rapidity with which many resistances have appeared after the introduction of a new antibiotic suggests that these resistance genes were already present somewhere in nature prior to clinical use. In the hospital setting, the most recent worrisome resistance traits to emerge include plasmid-mediated resistance to imipenem and to third-generation cephalosporins among nosocomial gram-negative bacteria, and the acquisition of resistance to vancomycin by enterococci. Methicillin-resistant staphylococci continue to be a problem and are increasingly resistant to numerous other agents such as rifampin and the newer fluoroquinolones. The most important resistances seen in community-acquired organisms include beta-lactam resistance in pneumococci and combined ampicillin and chloramphenicol resistance in Haemophilus influenzae. Shigellae resistant to essentially all commonly used oral agents are also a problem, particularly in developing countries. No end is in sight to the problem of antimicrobial resistance, and thus new strategies to prevent infections and control resistant organisms continue to be necessary.

Anti-Bacterial Agents↗
PubMed1992

[In vitro kinetics of the activity of fusidic acid and fluoroquinolones combinations against staphylococci according to methicillin-resistance phenotype. Implications for the treatment of osteoarticular infections].

The kinetics of the effect of fusidic acid and of two fluoropiperazinyl quinolones (ofloxacin and pefloxacin), used alone or in combination, on ten methicillin-susceptible or methicillin-resistant strains of staphylococci were studied. Little or no bactericidal effects were seen with fusidic acid. With ofloxacin and pefloxacin, the bactericidal effect was delayed and occurred only with high concentrations. Used in combination, fusidic acid and the fluoroquinolones exhibited no synergistic effects and occasionally antagonized each other in vitro. The methicillin-resistance phenotype of organisms had no influence on results.

Bone Diseases↗
PubMed1992

[Considerations on MRSA infections in relation to modern chemotherapy].

Before the antibiotic era of medicine began about 50 years ago, the prognosis for patients with severe staphylococcal infections was extremely poor. In the early 1940s, the introduction of penicillin G (PCG) temporarily solved the problem of staphylococcal infections, but the continued use of this agent caused the selection of resistant strains, which produced penicillinase. Accordingly, the value of PCG had seriously reduced by 1948. By then S. aureus had acquired multiple resistance to virtually all available systemic antibiotics, including aminoglycosides, tetracycline, chloramphenicol and the macrolides. The introduction of the semisynthetic penicillinase resistant penicillins (e.g., methicillin, oxacillin) and the 1st generation cephems brought about a general decline in the prevalence of multiply resistant S. aureus during the early 1960s. The strains of methicillin-resistant S. aureus (MRSA) were initially detected in 1961 in the United Kingdom, shortly after methicillin came into clinical use, and they have subsequently been isolated in many other parts of the world including Japan. In Japan, most strains of MRSA now represent high level resistance to all antibiotics, except for a few antibiotics, such as vancomycin and arbekacin, and therefore, they posed a serious problem clinically and epidemiologically, via immuno-suppressed inpatients, in particular, as the causative pathogen of nosocomial infection. The appearance and spread of such MRSA strains in Japan may be due to the extensive use of broad spectrum antibiotics, particularly the 3th generation cephems. It is now important to reconsider the modern chemotherapy which evoke serious drug-resistant mutants, such as MRSA.

Anti-Bacterial Agents↗
PubMed1992

In vitro activity of teicoplanin and vancomycin against gram-positive bacteria from human clinical and veterinary sources.

The minimum inhibitory concentration (MIC) of teicoplanin and vancomycin was determined by the agar dilution method for 186 Gram-positive bacteria from human clinical and veterinary sources. Teicoplanin MIC values were less than or equal to 4 micrograms/ml for 94% of staphylococci (group A, n = 52) and less than or equal to 2 micrograms/ml for all streptococci, enterococci, aerococci and pediococci (group B, n = 75). Seventy-eight percent of Gram-positive rods, Rhodococcus and Leuconostoc spp. (group C, n = 59) were inhibited by 4 micrograms/ml. Teicoplanin resistance (MIC greater than or equal to 16 micrograms/ml) was demonstrated for all Nocardia strains and for some strains of Lactobacillus, E. rhusiopathiae, Leuconostoc, and S. haemolyticus. Cross-resistance between teicoplanin and vancomycin was observed for all Nocardia strains and for some strains of Lactobacillus, E. rhusiopathiae, and Leuconostoc. Three methicillin-resistant S. haemolyticus strains were either resistant or intermediately susceptible to teicoplanin and susceptible to vancomycin. Eight strains (motile enterococci four, E. rhusiopathiae three and Leuconostoc sp. one) were susceptible to teicoplanin and resistant to vancomycin. Teicoplanin disc diffusion on Danish Blood Agar with NeoSensitabs (Rosco), PDM AB Biodisc and locally prepared discs revealed a wide range of zone diameters in groups B and C. The relation between MIC values and zone diameters for teicoplanin was analysed by the error-rate bounded method. Zone size interpretive criteria as suggested by the manufacturers (greater than or equal to 15 mm) produced 2.7% (95% confidence limits 0.9-6.2%) and 1.6% (95% confidence limits 0.3-4.6%) very major errors for NeoSensitabs and PDM-disc, respectively. Using a zone size breakpoint for susceptibility of greater than or equal to 25 mm for NeoSensitabs and greater than or equal to 20 mm for PDM-disc, the proportions of very major errors were 0.5% (95% confidence limits 0.0-3.0%) at the expense of 5.9% (95% confidence limits 3.0-10.3%) indeterminate strains that belonged to E. rhusiopathiae, Leuconostoc, Lactobacillus and S. haemolyticus. However, using these zone size breakpoints five major errors (beta-haemolytic streptococci, group B three, S. aureus one, Leuconostoc sp. one) were observed for NeoSensitabs and two major errors (beta-haemolytic streptococcus, group B one, Leuconostoc sp. one) were observed for PDM-disc. Susceptibility testing against teicoplanin among these taxa should therefore include a determination of MIC.

Animals↗
PubMed1991

[Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. I. Synergistic action with minocycline].

Since cefodizime (CDZM) shows a broad antimicrobial spectrum and relatively long half life in blood, we examined its synergistic action with minocycline (MINO) in vitro against Staphylococcus aureus. 1. CDZM in the presence of MINO, most of cases 1 MIC showed FIC index greater than 0.5-less than or equal to 2 against methicillin-susceptible S. aureus (MSSA), thus the results suggested a synergistic action against S. aureus. 2. CDZM in combination with MINO at 1 MIC or sub MIC where therapeutically a favorable efficacy is expected on MINO-susceptible strains exhibited FIC index less than or equal to 0.5-less than or equal to 1, Methicillin-resistant S. aureus (MRSA), thus suggesting a synergistic action against MINO-susceptible MRSA strains. Synergism was hardly recognized against MINO-resistant MRSA strains, however. 3. Synergism by both drugs was produced in MINO-susceptible strains of S. aureus including MRSA where MIC by CDZM was high or moderate, but no synergism was demonstrated against MINO-resistant strains. That is, synergistic action by both drugs was thought to depend on antimicrobial activity of MINO.

Cefotaxime↗
PubMed1991

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1988)].

Isolated bacteria from respiratory infectious diseases were collected in cooperation with institutions located throughout Japan, since 1981, and Ikemoto et al. have been examining sensitivities of the isolates to various antibacterial agents and antibiotics, relationships between the isolates and the backgrounds of the patients and so forth each year. We report here the research results for the year 1988. In 18 institutions around the entire Japan from October 1988 to September 1989, 554 strains of bacteria were isolated mainly from the sputa of 439 patients with respiratory infectious diseases and assumed to be the etiologic bacteria. MICs of various antibacterial agents and antibiotics against 68 strains of Staphylococcus aureus, 102 strains of Streptococcus pneumoniae, 120 strains of Haemophilus influenzae, 86 strains of Pseudomonas aeruginosa, 65 strains of Branhamella catarrhalis, 18 strains of Klebsiella pneumoniae and so forth, were determined, and the drug sensitivities of these strains were examined except for the strains which died during transportation. The drug sensitivities of the main strains were almost the same as those determined last year for each drug. However, S. aureus strains for which MICs of methicillin were higher than 12.5 micrograms/ml (methicillin-resistant S. aureus) accounted for 38.2%, and the frequency of drug resistant bacteria increased over last year's 18.2%. Also, we examined changes in the backgrounds of patients, the infectious diseases, and the etiologic bacteria and so forth. As to patient backgrounds, there were many infectious diseases found in a high age bracket, and the patients over age 60 accounted for 57.2% of the diseases. In the distribution by disease, bacterial pneumonia and chronic bronchitis accounted for greatest numbers of cases 32.1% and 31.4%, respectively, followed by bronchiectasis and bronchial asthma. As for frequencies of etiologic bacteria by disease, S. aureus (22.5%) and S. pneumoniae (15.4%) in pneumonia, S. pneumoniae (25.7%) and H. influenzae (24.1%) in chronic bronchitis, H. influenzae (32.5%) and P. aeruginosa (23.8%) in bronchiectasis, and H. influenzae (31.4%), S. pneumoniae and B. catarrhalis (20.0%) in bronchial asthma were the most frequent. Regarding effects of administration of antibiotics and isolates obtained on each day after infection, those bacteria which were isolated before antibiotic administration and which decreased after administration included S. pneumoniae, H. influenzae, and B. catarrhalis. Frequencies of S. aureus and P. aeruginosa, however, increased after antibiotic administration. Also, when dosing continued for more than 15 days, the frequency of P. aeruginosa increased rapidly.

Anti-Bacterial Agents↗
PubMed1991

[Antimicrobial activity of cefpiramide to fresh clinical isolates].

In the subjects of 835 strains of 37 clinically isolated microbial strains, which were separated and identified among materials collected from patients with various infections and which were sent from medical therapeutic institutions throughout Japan in 1990, for the purpose of examining the antimicrobial activity of cefpiramide (CPM), its minimum inhibitory concentration (MIC), together with those of other cephem antibiotics, was determined, and the following conclusions were obtained. 1. Microbial strains in which no CPM-resistant strains emerged were Streptococcus pyogenes, Streptococcus pneumoniae and Anaerobic Gram-positive cocci. 2. In comparison with reports by many researchers at the former half of the 1980s, microbial stains suggesting an increase in resistance to CPM were Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas cepacia, Pseudomonas putida, Acinetobacter calcoaceticus, and Haemophilus influenzae, but also in other microbial strains the resistance to CPM was observed in high ratios. 3. Among strains used in the test, methicillin-resistant S. aureus, cephamycin and oxime type cephalosporin-resistant Gram-negative bacilli of Enterobacteriaceae, and new quinolone-resistant microbes were observed in high ratios; therefore, it was considered that CPM could not exert sufficient antimicrobial activities to these strains because of many resistant strains being complicated among these "CPM-resistant strains". 4. It was discussed that "the resistance mechanism observed throughout beta-lactam drugs as a while and the study themes in the dimension including social circumstances where resistant strains emerged", as pointed out by the authors in 1989, increased the significance of these days in the evaluation of timecourse changes in microbes resistant to specific drugs including CPM. 5. There are many unfavorable conditions in the antimicrobial activities of CPM to clinically isolated strains in recent years. However, it was jointly confirmed that CPM maintained effective antimicrobial activities to the majority of clinically isolated strains. Furthermore, when it was additionally considered that CPM was one of not many cephem drugs having persistent blood levels, a conclusion was drawn that CPM was one of clincally useful cephem drugs even at present.

Anti-Bacterial Agents↗
PubMed1991

[Antibiotic sensitivity of bacteria isolated from patients at 6 hospitals in Osaka].

We examined MICs of 6 oral new quinolones and 4 oral cephems against bacteria isolated from patients at 6 hospitals in Osaka during the period from January to June in 1990, and the following results were obtained. 1. All species excluding Streptococcus pyogenes were more sensitive with less frequencies of resistance to new quinolones than to cephems. In new quinolones, tosufloxacin (TFLX) was the most active against Gram-positive cocci and ciprofloxacin (CPFX) and TFLX had the highest activities against Gram-negative rods. 2. Resistant (MIC of CPFX greater than or equal to 3.13 micrograms/ml) strains to new quinolones were observed at higher frequencies than 10% among Staphylococcus spp., Enterococcus faecalis, Citrobacter freundii, Morganella morganii, Providencia rettgeri, Serratia spp., Pseudomonas aeruginosa, Pseudomonas cepacia and Xanthomonas maltophilia. 3. The frequency of Staphylococcus aureus resistant to new quinolones isolated from in-patients or urine was significantly higher than that from out-patients or other sources. On the other hand, there was no significant difference in resistance frequencies of P. aeruginosa due to types of patients or sources. But, there were significant differences in frequencies of resistant organisms of either species to new quinolones among hospitals. 4. Twenty-seven strains (19.7%) of 137 S. aureus strains examined were methicillin-resistant, and they were similarly resistant to new quinolones also. Methicillin susceptible S. aureus were also similarly sensitive to new quinolones.

Anti-Bacterial Agents↗
PubMed1991

[Antibacterial activities of ofloxacin against recent isolates from patients with community-acquired infections].

In order to survey antibacterial activities of ofloxacin (OFLX) against 1,440 bacterial strains isolated from patients with community-acquired infections in 1987 and 1990, minimum inhibitory concentrations (MICs) of the drug as well as those of other new quinolones and oral cephems were determined. The following conclusions were reached. 1. Comparison of the MIC distribution for strains isolated in 1987 with those in 1990 suggested a tendency toward an increase in the frequency of OFLX-resistant isolates with the passage of time of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Citrobacter spp., Klebsiella ssp., Enterobacter spp., Proteus vulgaris, Morganella morganii, Providencia spp., and Acinetobacter calcoaceticus. Most common elevations of MIC values against these bacteria were observed in MIC80 and MIC90 values, while no significant alteration was observed in MIC50 values. However, MIC50's of OFLX against Serratia marcescens and Pseudomonas aeruginosa were relatively high for strains isolated in both 1987 and 1990. Most of the OFLX-resistant strains of S. aureus seemed to be methicillin-resistant (MRSA). Furthermore, MIC80 of OFLX against coagulase-negative staphylococci was high in strains isolated in both 1987 and 1990. 2. Susceptibility of Streptococcus spp. was evaluated only in strains isolated in 1990. The results were comparable to those reported by others in the early 1980s. 3. Bacteria which showed no or infrequent emergence of OFLX-resistant strains even in 1990 were Proteus mirabilis, Haemophilus influenzae, Neisseria gonorrhoeae, Campylobacter spp. and Peptostreptococcus spp. 4. Recently isolated strains from patients with community-acquired infections showed a tendency toward an increase of the frequency of OFLX-resistant strains among many bacteria. However, the bacteria which contained high percentages of OFLX-resistant strains except for MRSA were so-called less-virulent bacteria, and in the other bacteria elevations of MIC values were only observed in MIC80 and MIC90. These results suggested that OFLX preserved a potent antibacterial activity against bacteria which were major causative pathogens in community-acquired infections.

Bacteria↗
PubMed1990

[Detection of causative bacteria for bovine mastitis and their susceptibility to beta-lactam antibacterial agents].

During the period from November 1988 to May 1989, causative bacteria in a total of 172 clinical mastitis cases observed in 66 farms in 5 districts with 6 areas in Japan were examined and frequencies of their occurrences were determined. Susceptibilities (in MICs) of the isolates to 6 beta-lactam antibacterial agents were also determined. As a result, coagulase-negative staphylococci (CNS) was identified in 94 out of 172 cases (54.7%) and were the most prevalent. Corynebacterium spp., Gram-negative bacteria and Staphylococcus aureus were found in 52 (30.2%), 49 (28.5%) and 43 (25.0%) cases, respectively. Four species of Streptococcus family (S. agalactiae, S. dysgalactiae, S. uberis and S. bovis) were identified in a total of 58 cases (33.7%). Susceptibility testing of CNS to cefoperazone (CPZ), cefazolin (CEZ), benzylpenicillin (PCG), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) showed that all MIC80's (inhibiting bacterial growth of 80% of all isolates) were within a range from 0.10 to 3.13 micrograms/ml and that there was no marked differences in antibacterial effects among the antibiotics used. The highest antibacterial effect on S. aureus was exhibited by MCIPC, which inhibited the growth of all isolates at 0.39 microgram/ml. The MICs of DMPPC against all isolates of S. aureus were 3.13 micrograms/ml or less and no methicillin-resistant S. aureus (MRSA) was detected. There was no difference in antibacterial activities against Streptococcus family between penicillin antibiotics (DMPPC, MCIPC, ABPC and PCG) and cephem antibiotics (CPZ and CEZ), both of which showed excellent antibacterial activities. Cephem antibiotics exhibited higher activities against Gram-negative bacteria than penicillin antibiotics. Especially CPZ, the third generation cephem, showed excellent antibacterial activity against Escherichia coli, Klebsiella spp., Enterobacter spp., as well as against other Enterobacteriaceae.

Animals↗
PubMed1990

[Antimicrobial activities of gentamicin against fresh clinical isolates].

Antimicrobial activities of gentamicin (GM), compared with activities of other aminoglycosides (AGs) and beta-lactam antibiotics, were studied against clinical isolates obtained during a period of July-December 1989. 1. GM-resistant strains were noted in 24% of Staphylococcus aureus, 12% of Enterobacter spp., 24% of Serratia marcescens, 7% of Morganella morganii and 26% of Pseudomonas aeruginosa, but no GM-resistant strains were observed among isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris. 2. A majority of GM-resistant strains of S. aureus were methicillin-resistant S. aureus (MRSA) and a large number of GM-resistant strains of Enterobacter spp. was also resistant to new quinolones. GM showed, however, strong antimicrobial activities against new quinolones-resistant strains of S. marcescens, M. morganii and P. aeruginosa. 3. Among all the isolates tested of S. marcescens, 24% were GM-resistant, 72% were tobramycin (TOB)-resistant, 86% were dibekacin (DKB)-resistant and 64% were amikacin (AMK)-resistant, hence the incidence of GM-resistant strains was the lowest. This tendency was also observed with P. vulgaris. However, among P. aeruginosa, 26% were GM-resistant, 14% TOB-resistant, 18% DKB-resistant and 22% AMK-resistant, thus the incidence rate for GM-resistance was somewhat higher. These results suggest that different AGs-modification enzymes were produced by various clinical isolates under the present condition. 4. Comparing the ratio of GM-resistant strains in the present study with those in 1980 and 1983, the ratio increased among S. aureus, while decreases were observed among Enterobacter spp., S. marcescens, P. vulgaris and P. aeruginosa, indicating that a unilateral tendency of increases in GM-resistant strains did not exist among clinical isolates over the years.

Anti-Bacterial Agents↗
PubMed1990

[Bactericidal activity of imipenem].

The bactericidal activity of imipenem against Pseudomonas aeruginosa, Enterobacteriaceae and Staphylococcus aureus was compared with that of other antibiotics, using the time-related kill rate curve method. The activity of imipenem was found to be less rapid and less intense than that of aminoglycosides, similar to that of fluoroquinolones and more rapid than that of beta-lactam antibiotics, notably ticarcillin and ceftazidime against P. aeruginosa and cefotaxime against Enterobacteriaceae. As with aminoglycosides, this bactericidal activity was concentration-dependent against Enterobacteriaceae and S. aureus but not against P. aeruginosa. Unlike the beta-lactam antibiotics, but like aminoglycosides and fluoroquinolones, imipenem remained active against "quiescent" P. aeruginosa, though not against Enterobacteriaceae. Successive transfers into liquid media rapidly produced resistant variants among P. aeruginosa strains and methicillin-resistant S. aureus strains, but not among Enterobacteriaceae. This shows that the bactericidal activity of imipenem is markedly different from that of other beta-lactam antibiotics.

Acinetobacter↗
PubMed1990

[Annual changes in susceptibility of clinical isolates to midecamycin acetate].

To investigate annual changes in the susceptibility of clinical isolates to midecamycin acetate (MDM-AC), minimum inhibitory concentrations (MICs) of MDM-AC were determined for clinical isolates obtained from outpatients since 1985. MDM-AC-resistant strains of Staphylococcus spp. and Streptococcus spp. have shown similar degrees of resistance to midecamycin and josamycin. Regarding this as macrolide resistance, proportions of macrolide-resistant strains tended to increase for Staphylococcus aureus and Streptococcus pneumoniae but to decrease for Streptococcus pyogenes. 1. For S. aureus, 8% of the strains isolated in 1985, 20% in 1987 and 20% in 1989 were macrolide-resistant. Of these macrolide-resistant strains, 70% or more in 1987 and 80% or more in 1989 were methicillin-resistant S. aureus (MRSA). 2. For S. pneumoniae, 8% of the strains isolated in 1985, 12% in 1987 and 12% in 1989 were macrolide-resistant, indicating a tendency for resistant strains to increase annually. 3. For S. pyogenes, 8% of the strains isolated in 1985, 4% in 1987 and 0% in 1989 were macrolide-resistant, showing a decreasing tendency. 4. MDM-AC is still thought to be a clinically useful antibacterial agent because it still shows antibacterial activity against 80% or more of Gram-positive cocci clinically isolated in recent years and a low degree of induction of macrolide resistance in Staphylococcus spp.

Bacterial Infections↗
PubMed1990

[In vitro synergism of two-drug combinations among cefamandole, flomoxef and imipenem against MRSA].

First of all, vancomycin (VCM) showed good antimicrobial activity against Staphylococcus aureus including methicillin-sensitive and -resistant strains. MIC90 of VCM was 1.56 micrograms/ml. Effects of different 2-drug combinations among cefamandole (CMD), flomoxef (FMOX) and imipenem (IPM), and activity of VCM alone were examined in vitro against 5 clinical isolates of methicillin-sensitive S. aureus (MSSA) and 22 isolates of methicillin-resistant S. aureus (MRSA). In a checkerboard study, synergism was observed against 4 strains of the 5 MSSA and all 22 strains of the MRSA with IPM and CMD, FMOX and IPM, and FMOX and CMD combinations. Mean MICs of these combinations were as low as one-fourth to one-tenth as those of individual drugs.

Cefmetazole↗