In vitro activity of piperacillin compared with that of ampicillin, ticarcillin, azlocillin, and mezlocillin

The antibacterial activity of ampicillin, ticarcillin, azlocillin, mezlocillin and piperacillin was investigated in 1112 fresh clinical isolates using the microdilution technic. Ampicillin was the most active agent against enterococci and ticarcillin against Staphylococcus aureus, 91% of the latter being inhibited by 32 mg/l. 95% of strains of Pseudomonas aeruginosa were susceptible to piperacillin and 90% to ticarcillin and azlocillin. Piperacillin was still active against half of the azlocillin-resistant strains of Pseudomonas aeruginosa. Against the Enterobacteriaceae, mezlocillin and piperacillin were equally active: 31% of these strains were resistant to both drugs. Amongst the various strains the percentage of resistance was highest in Klebsiella (60%). Analysis of resistance patterns of Enterobacteriaceae showed almost completely parallel resistance between these two drugs the difference being less than 3%. Piperacillin, however, had the broadest spectrum of all the penicillins tested.     

Antibiotic resistance patterns in Pseudomonas aeruginosa: an 8-year surveillance study in a French hospital

The susceptibility to ticarcillin, piperacillin, ceftazidime, aztreonam, tobramycin, amikacin, ciprofloxacin and fosfomycin of 3876 strains of Pseudomonas aeruginosa isolated during the period 1989-1996 in a French hospital was investigated. The most frequently active agents were amikacin and ceftazidime to which 13.3% and 16.1% of the isolates were resistant. Analysis of beta-lactam susceptibility patterns suggested that cephalosporinase derepression and intrinsic resistance were the predominant underlying mechanisms. There was a trend towards a decline in susceptibility to beta-lactams, aminoglycosides and ciprofloxacin over time. Multiresistance was frequent, mainly in O11 and O12 isolates.     

Antibacterial activity of aztreonam: a synthetic monobactam. A comparative study with thirteen other antibiotics

The in vitro activity of aztreoman (SQ 26, 776), a new monocyclic beta-lactam antimicrobial agent, was determined against 1720 bacteria, all clinical isolates, and compared with that of thirteen beta-lactam and aminoglycoside antibiotics. Aztreonam inhibited 90% of Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris and Salmonella sp. by less than or equal to 0.4 micrograms ml-1. This activity was superior to moxalactam, piperacillin, cefamandole, cefoperazone, cefoxitin, cefsulodin, ceftazidime and aminoglycoside antibiotics. Aztreonam was as active as moxalactam against Enterobacter aerogenes, Enterobacter cloacae and Shigella species. Pseudomonas aeruginosa strains resistant to moxalactam, piperacillin, cefamandole, cefoperazone, cefotaxime, cefoxitin, cefsulodin and ceftazidime were inhibited by aztreonam 50% by 6.3 micrograms ml-1 and 90% by 16 micrograms ml-1. Aztreonam was as active as ceftazidime against Serratia marcescens, all strains were inhibited by 3.1 micrograms ml-1 and 90% by 1.6 micrograms ml-1. There was no major difference between MBC and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU.     

Antimicrobial use and Pseudomonas aeruginosa susceptibility profile in a cystic fibrosis centre

The susceptibility patterns of 1315 mucoid and non-mucoid Pseudomonas aeruginosa strains from 224 patients were determined along with antibiotic utilisation in a Cystic Fibrosis Centre from 1993 to 1997. Ceftazidime was the most active agent (86.0% sensitive isolates), followed by piperacillin-tazobactam (81.7%), aztreonam (80.3%), imipenem (80%), piperacillin (76.8%), tobramycin (76.5%), ciprofloxacin (73.7%), ticarcillin (72.4%), ticarcillin-clavulanic acid (70.2%), amikacin (69.5%), netilmicin (56.5%), meropenem (79%) and imipenem (75.5%). The most frequently used compounds were nebulized colistin (mean+/-S.D., 109+/-45 defined daily doses per 1000 patients per day), followed by ciprofloxacin (98+/-8), tobramycin (55+/-9), ceftazidime (31+/-8) and amikacin (55+/-9). The mean antibiotic consumption by our CF patients was 413+/-47 defined daily doses per 1000 patients per day. Trend testing showed a significant decline of susceptibility to aminoglycosides, imipenem and ciprofloxacin, while the susceptibility of P. aeruginosa to piperacillin and ceftazidime was stable.     

Susceptibility of Pseudomonas aeruginosa to aztreonam in comparison to other pseudomonas-active beta-lactam antibiotics and gentamicin

The in vitro activity of aztreonam, a synthetic monobactam, was evaluated against 245 strains of Pseudomonas aeruginosa, 130 of them being recent clinical isolates from patients and 115 from hospital environment. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bactericidal kinetics were determined. The possibility of resistance development in vitro was studied. Gentamicin, cefsulodin, piperacillin and azlocillin were used as comparative agents with known antipseudomonal activity. At a concentration of 8 mg/l 83.3%, at 16 mg/l 92% of the tested strains were susceptible to aztreonam. Thus, the activity of aztreonam against Pseudomonas aeruginosa is equivalent to that of gentamicin and cefsulodin and better than that of piperacillin and azlocillin in terms of resistance. Bactericidal kinetics with fourfold MIC, which is equivalent to MBC, are nearly identical for aztreonam, piperacillin and cefsulodin. In vitro induced resistance additionally causes increased resistance against the other beta-lactam antibiotics.     

Evaluation of antimicrobial activity of beta-lactam antibiotics using Etest against clinical isolates from 60 medical centres in Japan

An antimicrobial resistance surveillance study was carried out in 60 medical centres across Japan. Resistance to piperacillin was 10.8% in clinical isolates of Escherichia coli, while 1.3% or fewer isolates were resistant to other beta-lactams. Klebsiella spp. were more susceptible to imipenem, cefepime and cefpirome. Isolates of Enterobacter spp., Citrobacter spp., indole-positive Proteus and Serratia spp. were susceptible to imipenem, cefepime and cefpirome, while Acinetobacter spp. were most susceptible to cefoperazone/sulbactam, imipenem, ceftazidime (5.8% resistance) and cefepime (7.6%). Isolates of Pseudomonas aeruginosa were more susceptible to ceftazidime (12.3% resistance), cefoperazone/sulbactam (12.5%) and cefepime (12.6%) than to piperacillin (15.0%), cefpirome (22.6%) and imipenem (30.8%). The percentage of Japanese imipenem resistant P. aeruginosa clinical isolates was around 30%.     

In vitro antibacterial activity of imipenem against Pseudomonas and Staphylococcus species. Comparison with thirteen other antimicrobial agents

The in vitro antimicrobial activity of imipenem against recent clinical isolates of Pseudomonas spp. (94 strains) and penicillin-resistant Staphylococcus spp. (50 Staph. aureus and 50 coagulase-negative Staphylococcus) was assessed using the Mueller-Hinton agar dilution method. Results were compared with those simultaneously obtained for amikacin, netilmicin, tobramycin, norfloxacin, piperacillin, ceftazidime, ceftriaxone and azthreonam against Pseudomonas spp., and for rifampicin, clindamycin, netilmicin and cefoxitin, besides penicillin and methacillin, against Staphylococcus spp. About 50 and 90% of 84 Pseudomonas aeruginosa isolates were inhibited by concentrations of imipenem equal to or less than 2 and 8 mg/l respectively. The in vitro activity of imipenem was comparable to that of ceftazidime and norfloxacin, but superior to that of the aminoglycosides and all the other antibiotics tested, in terms of potency by weight. Among other Pseudomonas spp. only P. malthophilia (2 strains) proved resistant to imipenem. Rifampicin was the most active antibiotic by weight against Staph. aureus but imipenem was more active than clindamycin and, especially, netilmicin and cefoxitin. Imipenem was highly active also against coagulase-negative staphylococci, with some differences related to the high incidence of methicillin-resistant strains. MICs of imipenem in Mueller-Hinton broth correlated with those obtained in agar, unlike the aminoglycosides. There were no significant inoculum effects on MICs of imipenem and MBCs were within one twofold dilution of MICs in over 75% of assays.     

In vitro activity of piperacillin/tazobactam against isolates from patients enrolled in clinical trials

The in vitro activity of piperacillin alone or titrated with a constant concentration of 4 mug/ml tazobactam was evaluated against 3962 baseline pathogens isolated from 1899 patients enrolled in 9 clinical trial studies in North America. Tazobactam increased susceptibility rates of piperacillin for Enterobacteriaceae from 81% to 96%, Staphylococcus (methicillin susceptible) spp. from 6% to 100%, Bacteroides fragilis group from 79% to >99% and Haemophilus from 85% to 98%. The excellent activity of piperacillin against Pseudomonas, Streptococcus and Enterococcus was maintained in the presence of tazobactam. Overall piperacillin/tazobactam had better activity than ticarcillin/clavulanic acid, ceftazidime, and in general equaled the activity of imipenem. The excellent in vitro, extended-spectrum activity of piperacillin/tazobactam suggests its utility for various infections.     

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).     

Antimicrobial resistance among non-fermentative Gram-negative bacilli isolated from the respiratory tracts of Italian inpatients: a 3-year surveillance study by the Italian Epidemiological Survey

The Italian Epidemiological Survey evaluated antibiotic susceptibility of non-fermentative Gram-negative bacilli isolated from inpatient respiratory-tract specimens collected throughout Italy during 1997-1999. The minimal inhibitory concentrations of 14 antibiotics for 1474 Pseudomonas aeruginosa strains, 307 Stenotrophomonas maltophilia strains and 114 Acinetobacter baumannii strains were determined in 57 clinical microbiology laboratories by means of a standardised micro-dilution method. The most active drugs against P. aeruginosa isolates were meropenem (81% susceptible) and amikacin (80% susceptible). Imipenem and meropenem proved to be the only agents active against A. baumannii isolates, although 13 and 16%, respectively, of strains were resistant to these drugs. Trimethoprim-sulphamethoxazole (TMP-SMZ) showed activity only against S. maltophilia isolates (83% susceptible). A total of 185 multidrug-resistant P. aeruginosa isolates (resistant to piperacillin, ceftazidime, gentamicin, and imipenem) were found. Resistance rates and trends showed consistent regional variations, including sharp increases from 1997 to 1999 in imipenem resistance among P. aeruginosa isolates from central and southern Italy.     

In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains isolated from the lower respiratory tract of Intensive Care Unit patients with nosocomial pneumonia and receiving antipseudomonal therapy

Pseudomonas aeruginosa causes severe nosocomial pneumonia in Intensive Care Unit (ICU) patients, with an increased prevalence of multiresistant strains. We examined the impact of the use of antipseudomonal antibiotic(s) on the susceptibility of P. aeruginosa isolated from ICU patients with clinically suspected hospital-acquired pneumonia collected in five teaching hospitals (110 non-duplicate initial isolates; 62 clonal pairs of initial and last isolates during treatment). Minimum inhibitory concentrations (MICs) were determined for amikacin, ciprofloxacin, meropenem, piperacillin/tazobactam (TZP), cefepime and ceftazidime (used in therapy) as well as five reporter antibiotics (aztreonam, colistin, gentamicin, piperacillin and ticarcillin) using Clinical and Laboratory Standards Institute (CLSI) methodology. Susceptibility was assessed according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI breakpoints. Resistance rates prior to treatment exceeded 25% for cefepime, ceftazidime, piperacillin, ticarcillin and aztreonam (EUCAST and CLSI) and for gentamicin, TZP and colistin (EUCAST only). The highest rates of cross-resistance were noted for ceftazidime and cefepime and the lowest rate for amikacin. Mean MIC values were systematically higher in isolates from patients previously exposed (1 month) to the corresponding antibiotic. For clonal pairs, a systematic increase in MIC between initial and last isolates (significant for amikacin, cefepime, meropenem and TZP) was noted. There was a significant correlation between the use of antibiotics (adjusted for respective proportional use of each drug) and loss of susceptibility at the population level when using EUCAST breakpoints. The high level of resistance of P. aeruginosa in ICU patients with nosocomial pneumonia as well as its further increase during treatment severely narrows the already limited therapeutic options. Further observational studies and the development of early diagnosis for resistant isolates are warranted.     

Beta-lactamase activity of anaerobic bacteroides strains isolated from clinical samples and their susceptibility to antimicrobial agents

Beta-lactamase production and susceptibility to 13 antimicrobial agents (penicillin-G, amoxycillin, amoxycillin/clavulanic acid, cefoxitin, imipenem, clindamycin, metronidazole, piperacillin, ticarcillin, rifampicin, chloramphenicol, tetracycline and erythromycin) of 32 isolated Bacteroides strains were determined. The strains included 23 isolates of B. frugilis, 2 B. thetaioatomicron, 2 B. ovatus, 1 B. distasonis, 1 B. capillosus, 1 B. uniformis, 1 B. ureolyticus and 1 B. merdae. beta-Lactamase production was detected in 65% of the Bacteroides using the nitrocefin test, All the antibiotic agents showed excellent activity against beta-lactamase negative strains (for tetracycline, ticarcillin and clindamycin, 90% were susceptible, whereas for the other drugs, 100% were susceptible). beta-Lactamase-positive Bacteroides strains showed 95% susceptibility to metronidazole and rifampicin; 90% susceptibility to piperacillin and cefoxitin; 85% susceptibility to tetracycline and erythromycin; 80% susceptibility to clindamycin and amoxycillin/clavulanic acid, and 76% susceptibility to ticarcillin. All beta-lactamase-positive strains were found to be susceptible to imipenem and chloramphenicol.     

N-formimidoyl-thienamycin and norfloxacin against multiple-resistant Pseudomonas aeruginosa strains. Combined in vitro activity and comparison with 14 other antibiotics

The in vitro susceptibility of 54 multiple-resistant strains of Pseudomonas aeruginosa to 16 antipseudomonal agents were determined. The majority of these organisms were also beta-lactamase-producing strains. Norfloxacin, N-formimidoyl-thienamycin and aztreonam showed the best antipseudomonal activity, with minimum inhibitory concentrations for 90% of isolates (MIC90) of 2, 8, and 8 mg/l respectively. Of the aminoglycosides, only amikacin (MIC90 = 32 mg/l) showed satisfactory activity, whereas among beta-lactam antibiotics, cefotaxime, ceftriaxone and moxalactam (MIC90 = 32 mg/l) were more active than cefoperazone (MIC90 = 128 mg/l), cefsulodin (MIC90 = 128 mg/l), piperacillin (MIC90 = 512 mg/l) and azlocillin (MIC90 = 1024 mg/l). A synergistic or partially synergistic interaction (fractional inhibitory concentration index less than 1) was demonstrated in vitro against 37% of the strains when N-formimidoyl-thienamycin was combined with norfloxacin.     

Pathogen occurrence and antimicrobial resistance trends among urinary tract infection isolates in the Asia-Western Pacific Region: report from the SENTRY Antimicrobial Surveillance Program, 1998-1999

Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram-positive and -negative species. The most common causative uropathogens often have intrinsic or acquired resistance mechanisms which include ESBL production among enteric bacilli, multi-drug resistant staphylococci and non-fermentative Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter spp. and vancomycin-resistant Enterococcus spp. This study evaluates pathogen frequency and the resistance rates among urinary tract infection (UTI) pathogens in 14 medical centres in the Asia-Pacific region between 1998 and 1999. The isolates were referred to a central monitor for reference NCCLS broth microdilution testing, identification confirmation and patient demographic analysis. Over 50% of the 958 pathogens were Escherichia coli and Klebsiella spp. followed by P. aeruginosa, Enterococcus spp. and Enterobacter spp. Susceptibility for the three enteric bacilli was high for carbapenems (100%), 'fourth-generation' cephalosporins (cefepime 94.9-98.6%) and amikacin (> or = 93.0%). Beta-lactamase inhibitor compounds were more active against E. coli (piperacillin/tazobactam; > 90% susceptible) than the other two enteric species and all other tested agents had a narrower spectra of activity. The rank order of anti-pseudomonal agents was amikacin (91.5% susceptible)> imipenem > piperacillin/tazobactam > tobramycin > ceftazidime and cefepime (77.4 and 76.4% susceptible, respectively). Susceptibility to quinolones for the P. aeruginosa isolates was only 63.2-67.0%. Only one vancomycin-intermediate Enterococcus spp. (van C phenotype) was detected among the 103 strains tested. Newer fluoroquinolones (gatifloxacin; MIC(50), mg/l) were more potent against enterococci than ciprofloxacin (MIC(50), 2 mg/l) and high-level resistance to aminoglycosides was common (41.7%). The data presented are compared to studies of similar design from other areas which are part of the SENTRY surveillance network.     

Microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in paediatric febrile neutropenic oncology patients: comparison between two consecutive time periods with use of different antibiotic treatment protocols

This study was devised to look at trends in the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in paediatric febrile oncology patients. The retrospective study compared various microbiological aspects recorded for febrile oncology neutropenic patients treated with two different empirical antibiotic regimens (ceftazidime plus gentamicin during 1998–1999 and piperacillin/tazobactam plus amikacin during 2000–2002). Eighty-one bacteraemic episodes occurred in 41 patients. Overall, 132 (34 during 1998–1999 and 98 during 2000–2002) organisms were isolated: 84 (65%) Gram-negative bacteria, 39 (30%) Gram-positive bacteria and 7 (5%) fungi. Enterobacter spp. incidence decreased from 18 to 6% (P = 0.07) while the recovery rates of Gram-positive organisms increased from 24 to 32% (P = 0.4) during 2000–2002 compared with 1998–1999. MRSA were not isolated from any episode of bacteraemia. Five (18%) of the 28 Escherichia coli and Klebsiella spp. isolates were β-lactamase producers (80% [4/5] isolated during 2000–2002). Twenty-seven of 28, 27/27, 23/28, 20/25 and 27/28 of these isolates were susceptible to imipenem, piperacillin/tazobactam, gentamicin, ceftazidime and ciprofloxacin, respectively. Thirty-two of 34 (94%) and 60/74 (81%) of the Gram-negative organisms isolated during 2000–2002 were susceptible to piperacillin/tazobactam and ceftazidime, respectively (P = 0.076). No major differences in the microbial spectrum and antibiotic susceptibilities were recorded between the two consecutive study periods. An increase in the number of extended β-lactamase producing E. coli and Klebsiella spp. occurred during 2000–2002. All β-lactamase producing organisms were susceptible to piperacillin/tazobactam and initial empirical therapy with piperacillin/tazobactam was more appropriate than ceftazidime to cover most of the pathogens causing bacteraemia.     

Piperacillin (T-1220), a new semisynthetic penicillin: in vitro antimicrobial activity comparison with carbenicillin, ticarcillin, ampicillin, cephalothin, cefamandole and cefoxitin

Piperacillin (T-1220) is a new semisynthetic penicillin with an unusually broad spectrum of antimicrobial activity. In vitro comparisons of this drug with 6 other beta-lactam antimicrobics (ticarcillin, carbenicillin, ampicillin, cephalothin, cefamandole and cefoxitin) were conducted. These included minimal inhibitory concentrations (MIC) against 394 bacterial isolates, the minimal lethal concentrations (MLC) against 79 of those, as well as the effect of inoculum size on the MIC and MLC of the drugs. Piperacillin had significantly greater activity than did the other penicillins against Pseudomonas species and Klebsiella pneumoniae. Against P. aeruginosa piperacillin was 8- and 16-fold more active than ticarcillin and carbenicillin, respectively. The MLC of piperacillin rarely differed from the MIC by more than one log2 dilutions except against P. aeruginosa in which the MLC was 4-fold greater or more than the MIC of 45% of isolates tested. Ticarcillin, carbenicillin and cefoxitin showed minimal inoculum size effects. Cefamandole results showed the greatest inoculum size variation with 55% and 37% of isolates showing an 8-fold increase in MIC and MLC respectively by increasing inoculum from 10(5) to 10(7) CFU/ml. Piperacillin was intermediately effected having 25% of strains greater than 8-fold increase in MIC.     

The resistance of recent clinical isolates against isepamycin, other aminoglycosides and injectable beta-lactams

Clinical isolates collected from clinical facilities across Japan in 1998 were tested against five aminoglycosides and three beta-lactams. The resistance of 50 strains each of methicillin sensitive Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter sp., Serratia sp., Pseudomonas aeruginosa and Proteus sp. (P. mirabilis 25 strains and P. vulgaris 25 strains) to the aminoglycosides isepamicin (ISP), amikacin (AMK), gentamicin, tobramycin and dibekacin, and to the beta-lactams imipenem, ceftazidime and piperacillin (all three known to be effective against P. aeruginosa) were investigated using a micro liquid dilution method with the following results: 1. ISP was effective against all strains except for 14% of MRSA, 2% of Proteus sp., and 4% of P. aeruginosa. 2. Six strains of MRSA were resistant to all eight drugs; however, in these cases ISP exhibited a relatively low minimum inhibitory concentration (MIC) compared to the other compounds. 3. Four strains of MRSA were resistant to all drugs except ISP. MRSA was the only isolate to demonstrate a resistance to seven or more drugs. 4. Twenty-one strains of MRSA and 1 strain of P. aeruginosa were resistant to six drugs; however, all of these were susceptible to both ISP and AMK. 5. Against all strains tested, ISP generally exhibited a lower MIC compared to AMK. These results suggest that, even ten years after its entering the market, ISP is still an aminoglycoside having a high anti-bacterial activity against a wide range of clinical isolates.     

Susceptibility patterns of Gram-negative bacteria from a Polish intensive care unit, 1997-2000

The susceptibility of Gram-negative bacterial strains (n=400) isolated from clinical specimens of children hospitalized in a Polish intensive care unit (ICU) between 1997 and 2000 was tested. Meropenem, imipenem and ciprofloxacin were most active (>90% susceptibility) against the tested isolates, with no observed reduction in activity over 4 years. Extended-spectrum beta-lactamases and AmpC beta-lactamase producers among Enterobacteriaceae isolates from this ICU continued to be a serious therapeutic problem, although the carbapenems were highly active against these resistance phenotypes. Resistance to aminoglycosides (gentamicin, tobramycin) and ceftazidime was a characteristic of >40% of tested isolates.     

Comparative in vitro activity of LY 127935 (6059-S), seven cephalosporins, three aminoglycosides, carbenicillin, and ticarcillin

LY 127935 (6059-S), a new semi-synthetic beta-lactam antibiotic was tested simultaneously with 6 cephalosporins, 3 aminoglycosides, carbenicillin and ticarcillin against 398 clinical isolates of Gram-negative bacilli and Gram-positive cocci. Many of the organisms were selected for study because of known resistance to one or more of the clinically available antibiotics tested. Escherichia coli, Klebsiella, Serratia and Providencia were susceptible to LY 127935. Some resistant strains of Enterobacter, Proteus, Pseudomonas aeruginosa and Acinetobacter were also resistant to LY 127935, but many of the strains resistant to other antibiotics were susceptible to LY 127935. The activity of LY 127935 against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans and Streptococcus bovis was similar to that of cephalexin and cephradine. LY 127935 was not active against methicillin-resistant S. aureus nor enterococcus.     

Synergy of fosfomycin with beta-lactam antibiotics against staphylococci and aerobic gram-negative bacilli

Fosfomycin inhibits bacterial cell wall synthesis at the initial stage. It can act synergistically with beta-lactams. The effect of the combination of fosfomycin and selected penicillins and cephalosporins against staphylococci, Pseudomonas aeruginosa, Pseudomonas cepacia and selected Gram-negative bacteria was determined. Synergy was determined by agar dilution and checkerboard titration methods; synergy was defined as an FIC index less than or equal to 0.5 and partial synergy greater than 0.5 to 0.75. Concentrations of drugs used were those that would be reached in man by intravenous and oral routes. Fosfomycin combined with nafcillin and with cefotaxime against staphylococci showed synergy for most isolates. For methicillin-resistant Staphylococcus aureus, synergy or partial synergy was found for 90% of isolates. Synergy was less frequently found with Staphylococcus epidermidis. The MICs for S. aureus were reduced from greater than or equal to 32 micrograms/ml to less than or equal to 1 microgram/ml. Fosfomycin was synergistic with ticarcillin, piperacillin, azlocillin, ceftazidime, aztreonam and imipenem against 31 to 61% of P. aeruginosa. MICs were reduced from greater than or equal to 128 micrograms/ml to 8-32 micrograms/ml, depending upon the agent. Although fosfomycin acted synergistically with azlocillin, piperacillin and ceftazidime against some P. cepacia, most often there was an indifferent interaction and MICs were in the resistant range, greater than or equal to 128 micrograms/ml. The interaction of fosfomycin and ampicillin was synergistic against a number of strains of Enterobacteriaceae, Proteus vulgaris and Providencia rettgeri, yielding MICs in an achievable range. The combination of fosfomycin with beta-lactams may be clinically useful in selected situations, particularly for methicillin-resistant staphylococci and beta-lactam-resistant P. aeruginosa.