Bactericidal activity and killing rate of serum against gram-positive cocci in volunteers receiving imipenem, oxacillin, vancomycin or ampicillin plus gentamicin

The serum bactericidal activity and rate of killing of serum was studied in two groups of ten volunteers receiving imipenem 500 mg, oxacillin 3 g and vancomycin 1 g given iv (Group 1) or imipenem 500 mg, vancomycin 1 g, and ampicillin 3 g plus gentamicin 80 mg iv (Group 2). Serum samples collected 30 min, 1 h and 6 h after the start of a 15 min infusion were tested against Staphylococcus aureus susceptible (five strains) or resistant (five strains) to oxacillin, Staphylococcus epidermidis susceptible to (five strains) or resistant (five strains) to oxacillin (Group 1), and against Streptococcus faecalis (four strains), Streptococcus spp. (six strains). All strains of streptococci had been isolated from patients with endocarditis. Imipenem produced the highest bactericidal titres against susceptible staphylococci whereas vancomycin produced the highest titres against oxacillin-resistant staphylococci. Against "non faecalis" streptococci, imipenem was equivalent to ampicillin plus gentamicin, whereas ampicillin plus gentamicin was the most active regimen against Str. faecalis. The study of the rate of killing of serum showed that imipenem was able to kill initially 1.5 log cfu/ml of Str. faecalis but this was followed by regrowth. A similar regrowth was observed with oxacillin-resistant staphylococci. Killing curves in broth were studied with imipenem at two temperatures (30 and 37 degrees C) and two initial inocula (10(5) and 10(6) cfu/ml) for 48 h of incubation against oxacillin-resistant staphylococci; regrowth occurred more rapidly with a high initial inoculum and low temperature of incubation despite a rapid initial killing. Gentamicin was found significantly to increase the rate of killing of imipenem against Str. faecalis in killing curves in broth. In conclusion, imipenem showed excellent activity, as assessed by the measure of the bactericidal titres and rate of killing in serum, against the studied strains with the exception of oxacillin-resistant staphylococci and Str. faecalis.     

Penicillin-induced effects on streptomycin uptake and early bactericidal activity differ in viridans group and enterococcal streptococci.

In vitro studies with penicillin and [3H]streptomycin in four strains of streptococci (S. faecalis, S. sanguis, and S. mitis) were performed by simultaneously measuring the rates of bacterial killing and uptake of streptomycin. In S. faecalis, penicillin stimulated streptomycin uptake, as has been shown by Moellering and Weinberg (R. C. Moellering, Jr., and A. N. Weinberg, J. Clin. Invest. 50:2580-2584, 1971). Moreover, the antibiotic combination was associated with an enhanced bactericidal rate which temporally correlated with beta-lactam-induced aminoglycoside uptake. In contrast, in viridans group streptococci (S. sanguis and S. mitis) penicillin had no effect on streptomycin uptake and a minimal effect on bactericidal rate when compared with either drug alone. These data suggested that the stimulation of streptomycin uptake in streptococci by penicillin is strain or species specific and that important differences exist between enterococci and viridans group streptococci regarding the mechanisms of beta-lactam-aminoglycoside potentiation.     

Effects of combinations of beta-lactams, daptomycin, gentamicin, and glycopeptides against glycopeptide-resistant enterococci.

Activities of combinations of beta-lactams, daptomycin, gentamicin, teicoplanin, and vancomycin against 11 clinical isolates of Enterococcus faecium highly resistant to glycopeptides, three plasmid-cured derivatives, eight E. faecalis and E. faecium transconjugants, and two susceptible recipient strains were tested. A marked synergy between penicillins or imipenem and glycopeptides against the glycopeptide-resistant strains but not against the glycopeptide-susceptible strains was observed by the double-disk agar diffusion assay. The synergy of combinations of amoxicillin, imipenem, penicillin G, or piperacillin with vancomycin or teicoplanin against resistant strains was confirmed by the checkerboard technique. The fractional inhibitory concentration indexes were generally below 0.25, except for one strain of E. faecium resistant to high levels of penicillin G. However, the combinations were not bactericidal as tested by time-killing experiments, and high concentrations (64 micrograms/ml) of amoxicillin, penicillin G, or piperacillin combined with 8 micrograms of vancomycin or teicoplanin per ml tended to be antagonistic. Addition of 4 micrograms of gentamicin per ml to these combinations enhanced their bactericidal effect, but they occasionally remained slightly less effective than beta-lactams associated with gentamicin. The combination of 10 micrograms of daptomycin per ml with gentamicin was bactericidal after 6 h against 11 glycopeptide-resistant strains.     

Antibiotic Susceptibility of Streptococcus bovis and Other Group D Streptococci Causing Endocarditis

Seventy-four strains of Streptococcus bovis and 35 strains of enterococci (Streptococcus faecalis and its varieties, Streptococcus faecium and Streptococcus durans), most of which were isolated from patients with endocarditis, were tested for their susceptibility to penicillin, ampicillin, erythromycin, cephalothin, vancomycin, methicillin, tetracycline, chloramphenicol, kanamycin, streptomycin, and gentamicin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined by a microtiter broth dilution technique. All of these organisms are group D streptococci, but the S. bovis strains are not enterococci. On the basis of both MIC and MBC, the S. bovis strains were much more susceptibile in general to antibiotics then were the enterococcal strains. For the S. bovis strains, the lowest MICs were obtained with penicillin, ampicillin, and erythromycin, and the lowest MBCs with penicillin and ampicillin. Although these antibiotics were also the most active against the enterococci, the MICs and MBCs were much higher than obtained with the S. bovis strains. Gentamicin was the most active aminoglycoside. On the basis of in vitro susceptibility results, the S. bovis strains resemble the viridans streptococci rather than enterococci.     

Effect of gentamicin dosing interval on therapy of viridans streptococcal experimental endocarditis with gentamicin plus penicillin.

This study compares the effects of a total daily dose of gentamicin given once a day (q.d.) or three times a day (t.i.d.) in the therapy of experimental endocarditis in rabbits caused by penicillin-susceptible, penicillin-tolerant, or penicillin-resistant viridans streptococci. Four isolates were used in vivo: one penicillin susceptible (MIC < or = 0.03 microgram/ml), one penicillin tolerant (MBC/MIC, < or = 0.03/ > 32 micrograms/ml), and two penicillin resistant (MICs = 0.5 and 2 micrograms/ml). Animals were infected with one of the four isolates and assigned to one of the following treatment regimens: no treatment, procaine penicillin at 1.2 million IU intramuscularly (i.m.) t.i.d., procaine penicillin plus gentamicin at 1 mg/kg of body weight i.m. t.i.d., procaine penicillin plus gentamicin at 3 mg/kg i.m. q.d., or procaine penicillin plus gentamicin at 1 mg/kg i.m. q.d. (only animals infected with the penicillin-susceptible isolate). Serum drug concentrations measured 30 min after administration of 1.2 million IU of penicillin and 1 or 3 mg of gentamicin per kg were 22.6, 3.8, and 8.5 micrograms/ml, respectively. The reduced total daily dose of gentamicin was ineffective among animals infected with penicillin-susceptible viridans streptococci; treatment with 1 mg of gentamicin per kg per day plus penicillin was less effective (P < 0.05) than was treatment with 3 mg of gentamicin per kg per day plus penicillin. The 1-mg/kg/day gentamicin treatment regimen was not further studied. The gentamicin dosing interval did not significantly affect (q.d. versus t.i.d., P > 0.05) the relative efficacy of penicillin plus gentamicin for treatment of experimental endocarditis among animals infected with each of the four isolates tested.     

In vitro bactericidal synergy of gentamicin combined with penicillin G, vancomycin, or cefotaxime against group G streptococci.

The in vitro bactericidal interactions of penicillin G, cefotaxime, or vancomycin in combination with gentamicin were compared against 20 group G streptococci by the timed kill curve method. Synergy was noted at the following frequencies: penicillin plus gentamicin, 80%; cefotaxime plus gentamicin, 85%; vancomycin plus gentamicin, 90%. There was no bactericidal antagonism observed.     

Synergy of Penicillin-Netilmicin Combinations Against Enterococci Including Strains Highly Resistant to Streptomycin or Kanamycin

The in vitro activity of combinations of penicillin and netilimicin was determined against 20 clinical isolates of enterococci and compared with that obtained in simultaneous tests with penicillin/sisomicin, penicillin/streptomycin, and penicillin/kanamycin. Synergy between the two drugs in each combination was determined by the use of quantitative kill curves and was defined as a killing by the combination at least 100-fold greater than that produced by the most effective drug alone. Penicillin/netilmicin and penicillin/sisomicin combinations were found to be synergistic against the majority of isolates tested, including strains resistant to penicillin/streptomycin or penicillin/kanamycin combinations. This synergy with penicillin could be demonstrated at a concentration of 相似文献   

Synergy of penicillin and decreasing concentration of aminoglycosides against enterococci from patients with infective endocarditis.

To determine whether low concentrations of aminoglycosides in combination with penicillin could effectively kill enterococci in vitro, we tested penicillin (20 micrograms/ml) in combination with decreasing concentrations of either streptomycin (20, 10, 5, and 1 micrograms/ml) or gentamicin (5, 3, 1, and 0.5 micrograms/ml) against 13 strains of streptomycin-susceptible and 7 strains of streptomycin-resistant enterococci isolated from patients with infective endocarditis. At 24 h, penicillin plus each increment in streptomycin concentration resulted in a statistically significant increase in killing of streptomycin-susceptible enterococci, compared with the next lower streptomycin concentration (P less than 0.01). At 24 h, against streptomycin-susceptible and streptomycin-resistant enterococci, there were no statistically significant differences in killing between combinations containing 5 micrograms of gentamicin per ml and those containing 3 micrograms/ml. Against streptomycin-susceptible enterococci, there were statistically significant differences in killing between combinations containing 3 micrograms of gentamicin per ml and those containing 1 micrograms/ml. Against streptomycin-resistant enterococci, statistically significant differences in killing were detected with combinations containing 5 micrograms of gentamicin per ml and those containing 1 microgram/ml.     

AZD2563, a new oxazolidinone: bactericidal activity and synergy studies combined with gentamicin or vancomycin against staphylococci and streptococcal strains

AZD2563, a novel oxazolidinone, was tested against 10 well characterized multiple-resistant strains of staphylococci and viridans group or beta-hemolytic streptococci using kill curve kinetic methods. Generally, AZD2563 demonstrated bacteriostatic action and modest concentration-dependent cidal activity against a minority of strains of both genera. When combined with gentamicin (MIC/4 concentration), rapid bactericidal action was observed against all streptococci tested, but not against the staphylococci. No enhanced activity was noted when AZD2563 was added to subinhibitory concentrations of vancomycin. Linezolid used as a control, showed the same characteristics, confirming that AZD2563 possesses activity comparable to other agents in the oxazolidinone class. AZD2563 remained active (MIC, < or = 1 microg/ml) against all 10 strains tested.     

A comparison of the in-vitro activity of seventeen antibiotics against Streptococcus faecalis

The in-vitro activity of seventeen antibiotics against 177 clinical strains of Streptococcus faecalis was evaluated. Ampicillin and mezlocillin were the most active beta-lactams tested (geometric mean MICs, 0.61 and 0.74 mg/l, respectively). Aminoglycosides showed poor activity and 22.6% of the strains were resistant to 2000 mg/l of streptomycin. No correlation was observed between MICs of gentamicin and streptomycin. Moderate activity was observed when testing norfloxacin and ciprofloxacin. Teicoplanin and co-trimoxazole were extremely active, showing geometric mean MICs of 0.59 and 0.08 mg/l respectively. All strains were susceptible to vancomycin and teicoplanin.     

Inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 56647) and five comparative antibiotics, used singly and in combination, against vancomycin-resistant and vancomycin-susceptible enterococci

The inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 66647) were compared with those of gentamicin, ampicillin, erythromycin, azithromycin and vancomycin against 74 strains of enterococci (34 Enterococcus faecalis and 40 Enterococcus faecium) by agar dilution, broth dilution, time kill assays and postantibiotic effect (PAE). The telithromycin MIC(90) for vancomycin-sensitive (VSE) E. faecalis strains tested using the agar dilution method was 8 microg/ml. For a different group of VSE E. faecalis strains tested using the broth dilution method it was 0.06 microg/ml The telithromycin MIC(90)s for vancomycin-resistant (VRE) and VSE E. faecium strains, determined using the agar dilution method, were 4 and 8 microg/ml, respectively, while for a different set of VRE and VSE E. faecium strains tested using the broth macrodilution method, they were 32 and 16 microg/ml, respectively. Telithromycin MBC(90)s for E. faecalis were 4-6 tubes higher and for E. faecium 3-5 tubes higher, respectively, than the MIC(90)s. In time kill assays, telithromycin had bactericidal activity against only 1 of 7 E. faecium strains; for all other E. faecium and E. faecalis strains, only inhibitory activity was demonstrated. Neither synergy nor drug interference was observed when telithromycin was used in combination with ampicillin, vancomycin or gentamicin. At 10 times the MIC, the PAE of telithromycin against E. faecalis was 2.8 h, while for E. faecium it was 1.6 h. Telithromycin should be evaluated for therapy of enterococcal infections, including those caused by VRE organisms. However, because of the strain-to-strain variability in susceptibility to telithromycin, MIC determinations are important, especially for erythromycin-resistant strains.     

Antibacterial Activity of Netilmicin, a New Aminoglycoside Antibiotic, Compared with That of Gentamicin

The antibacterial activity of netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was compared with that of gentamicin against a variety of gram-negative bacteria, staphylococci, and streptococci. Both antibiotics had similar activity against most organisms, but netilmicin had appreciably greater activity against gram-negative organisms that were resistant to gentamicin because these species synthesized aminoglycoside 3-N-acetyltransferase I or aminoglycoside 2'-O-nucleotidyltransferase. Netilmicin was also more active than gentamicin against gentamicin-resistant strains of Staphylococcus aureus that produced two enzymes-aminoglycoside-2'-O-phosphotransferase and aminoglycoside-6'-N-acetyltransferase.     

In Vitro Studies with Sch 21420 and Sch 22591: Activity in Comparison with Six Other Aminoglycosides and Synergy with Penicillin Against Enterococci

In vitro tests were performed with Sch 21420 and Sch 22591 to determine (i) their activity in comparison to six other aminoglycosides against 343 clinical isolates, and (ii) whether synergy with penicillin G could be demonstrated with enterococci. In broth dilution tests, Sch 22591 was more active than the seven other aminoglycosides against Staphylococcus aureus, Enterobacteriaceae, and most nonfermenting gram-negative bacilli. Sch 22591 was as active as tobramycin against Pseudomonas aeruginosa. The activity of Sch 21420 was comparable to gentamicin, sisomicin, netilmicin, and tobramycin but greater than amikacin or kanamycin against S. aureus and most genera of Enterobacteriaceae. Sch 21420, amikacin, and kanamycin were (i) more active than the other five aminoglycosides against Proteus rettgeri and Providencia stuartii, but (ii) less active than the other five aminoglycosides against Neisseria gonorrhoeae, enterococci, most nonfermenting gram-negative bacilli, Proteus mirabilis, and Proteus morganii. Studies on the bactericidal activity of Sch 22591 with penicillin indicated a synergistic interaction against enterococci, including strains highly resistant to streptomycin and kanamycin. This could be demonstrated with combinations containing 3.0 to 6.0 μg of Sch 22591 per ml and was comparable to that observed with penicillin/gentamicin. Penicillin plus Sch 21420 (25 μg/ml) also demonstrated synergy against enterococci, including strains highly resistant to streptomycin. However, synergy did not occur against strains highly resistant to kanamycin. These latter results were similar to those obtained in tests with penicillin/kanamycin.     

Daptomycin tested against 915 bloodstream isolates of viridans group streptococci (eight species) and Streptococcus bovis

OBJECTIVES: To evaluate the activity of daptomycin tested against numerous species of viridans group streptococci and Streptococcus bovis, which are associated with wound infections, sepsis, cellulitis, endocarditis, abscesses and dental caries. The incidence of penicillin-resistant (non-susceptible) and MLS(B)-resistant strains among viridans group streptococci often varies by species. METHODS: The activity of daptomycin was compared with seven other antimicrobial classes using reference broth microdilution and disc diffusion methods tested against 915 bacteraemic isolates of streptococci (815 viridans group strains; 100 S. bovis). RESULTS: Among all species of viridans group streptococci and S. bovis, 99.9% of isolates were susceptible to daptomycin (MIC values, < or = 0.016-2 mg/L). In contrast, penicillin, erythromycin and tetracycline susceptibility varied widely between species. Erythromycin susceptibility was in the range 48.6-88.7%, penicillin susceptibility in the range 65.5-98.1% and tetracycline in the range 35.0-93.9%. The inter-method agreement between daptomycin and linezolid resistance (comparison agent) disc diffusion and broth microdilution test results was high, each showing near complete susceptibility (99.9%). CONCLUSIONS: Daptomycin is an active antimicrobial agent that has a usable potency against eight species of viridans group streptococci, as well as S. bovis, with all MIC values at < or =2 mg/L.     

Antimicrobial Susceptibility of Streptococcus mutans Isolated from Patients with Endocarditis

Forty-one strains of Streptococcus mutans (34 from blood specimens from patients with endocarditis and 7 from stock cultures) were tested for susceptibility to penicillin, ampicillin, methicillin, erythromycin, cephalothin, vancomycin, chloramphenicol, tetracycline, gentamicin, streptomycin, and kanamycin. Minimal inhibitory and bactericidal concentrations were determined by a broth microdilution procedure. Most of the strains were very susceptible to ampicillin, penicillin, and erythromycin, with most strains having minimal inhibitory concentrations of 0.08 mug/ml or less. Most of the strains were also susceptible to cephalothin, methicillin, chloramphenicol, tetracycline, and vancomycin. Gentamicin was the most effective aminoglycoside. The antimicrobial susceptibility patterns are similar to those of other viridans streptococci. S. mutans strains have proven to be difficult for some microbiologists to identify. But when organisms suggesting S. mutans are isolated from patients with endocarditis, they should be at least identified as nonenterococcal streptococci so that appropriate therapy can be initiated.     

In vitro activity of piperacillin, ticarcillin, and mezlocillin alone and in combination with aminoglycosides against Pseudomonas aeruginosa.

A total of 103 isolates of Pseudomonas aeruginosa were studied to compare the in vitro effectiveness of three beta-lactam antibiotics (piperacillin, ticarcillin, and mezlocillin) when used alone and in combination with four aminoglycosides (tobramycin, gentamicin, amikacin, and netilmicin). All drugs were tested as single agents against a standard inoculum (5 X 10(5) CFU/ml). The three antipseudomonal penicillins were also tested against the isolates at a higher inoculum concentration (10(7) CFU/ml). Synergy testing was performed by the two-dimensional checkerboard method and was defined by a fractional bactericidal index of less than or equal to 0.5 and bacterial killing accomplished at antibiotic concentrations no greater than those achievable in serum. All combinations were assessed for synergy. The degree of synergy was further analyzed by dividing the isolates into groups based on their susceptibility and resistance to the individual agents in the combination. The overall effectiveness of the various aminoglycoside-antipseudomonal penicillin combinations was assessed regarding their ability to kill the isolates either as single agents or through synergy. Piperacillin was the most active antipseudomonal penicillin, and tobramycin and amikacin were the most active aminoglycosides when used as single agents. When tested against isolates at a higher inoculum concentration, ticarcillin was significantly more active than the other beta-lactams. The highest degree of overall synergy was noted with gentamicin-ticarcillin (78.2% of strains) and amikacin-piperacillin (77% of strains). When assessed for overall effectiveness, all combinations containing amikacin were the most active. The combination of amikacin-piperacillin was the most effective, with activity against 96% of all isolates.     

In Vitro Activity of Netilmicin, Gentamicin, and Amikacin

The in vitro activity of netilmicin (Sch 20569), a new semisynthetic derivative of gentamicin, was compared with that of gentamicin and amikacin. One hundred and ninety-two clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested using both agar and broth dilution techniques. Netilmicin was comparable to gentamicin, with the following exceptions: (i) for Serratia marcescens and P. aeruginosa, gentamicin was more active than netilmicin; (ii) all strains of Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, and Citrobacter freundii, which were resistant to gentamicin, were susceptible to netilmicin; (iii) some strains of S. marcescens, indole-positive Proteus, and Providencia, which were resistant to gentamicin, were susceptible to netilmicin. Netilmicin was more active than amikacin for all Enterobacteriaceae and S. aureus and equal to amikacin in activity against gentamicin-susceptible strains of P. aeruginosa. All strains of P. aeruginosa, resistant to gentamicin, were also resistant to netilmicin but were susceptible to amikacin. Minimal inhibitory concentrations (MICs) obtained with broth and agar showed no significant differences except for P. mirabilis, where broth MICs were twofold greater than agar MICs, and for P. aeruginosa, where agar MICs were twofold higher than broth MICs. The minimal bactericidal concentration (MBC) was either identical to or within one twofold dilution of the MIC for the strains tested. A 100-fold increase in inoculum size produced less increase in MIC and MBC with netilmicin than with gentamicin or amikacin.     

Activity and mechanism of action of DuP 105 and DuP 721, new oxazolidinone compounds

The in-vitro activities of DuP 721 and DuP 105, new oxazolidinone antibacterials, were compared with those of cefazolin, cephalexin, ciprofloxacin, clindamycin, oxacillin, penicillin, and vancomycin against Gram-positive cocci. DuP 721 was approximately four-fold more active than DuP 105 with an MIC of 2.0 mg/l for 90% of the Staphylococcus aureus, beta-haemolytic streptococcus and Streptococcus faecalis strains tested, and an MIC of 4.0 mg/l for 90% of the Str. faecium, penicillin-resistant Str. pneumoniae and viridans streptococcus strains tested. DuP 105 was most active against strains of Staph. epidermidis with an MIC of 4.0 mg/l for 90% of the strains tested. There was no cross resistance between these and the other antibacterial agents that were tested. Both oxazolidinones had bacteriostatic activity in broth against susceptible organisms. Both DuP 721 and DuP 105 inhibited ribosomal protein synthesis in a cell-free system. These synthetic, orally absorbable compounds represent a new series of antibacterial agents unrelated by chemical structure to any other currently available antimicrobial agents.     

Synergism, killing kinetics, and antimicrobial susceptibility of group A and B streptococci.

The susceptibility of 110 group A and 179 group B streptococci to 25 antimicrobics was tested by broth microdilution and agar disk diffusion tests. Representative strains were used in killing kinetics, penicillin-gentamicin synergy, and minimal bactericidal concentration tests. Group A streptococci were more susceptible than group B streptococci to 17 of the 25 antimicrobics tested. Group A and B streptococci were killed at the same rate if the amount of penicillin used was equivalent to their respective penicillin minimal inhibitory concentrations. Synergism was demonstrated for both group A and B streptococci when penicillin was used at concentrations equal to each respective minimal inhibitory concentration and subinhibitory concentration of gentamicin. This synergy could be demonstrated best using minimal bactericidal concentrations obtained by culturing 3- and 6-h cultures from the microdilution checkerboard tests rather than from 24-h subcultures. A greater synergistic effect was achieved by adding penicillin first and then adding gentamicin rather than in the reverse order, or simultaneously.     

Activity in vitro of CGP 31608, a new penem antibacterial agent

The in-vitro activity of CGP 31608 (hereinafter termed CGP), a new penem, was tested by an agar dilution technique in comparison with imipenem, Sch 34343, cefotaxime, ceftazidime, aztreonam, ampicillin, gentamicin and ciprofloxacin. 480 clinical isolated were tested, some of which were selected because of their multiple resistance. CGP showed consistent activity against a wide range of species, having MIC90 values of 2-8 mg/l for almost all Enterobacteriaceae, Pseudomonas spp., Haemophilus spp., Corynebacterium spp. and Bacteroides spp. It was the most active agent tested against staphylococci having an MIC90 of 0.25 mg/l, showing no reduction in activity against methicillin-resistant strains. Lesser activity was observed against some streptococci, Proteus spp. and clostridia. Tests carried out in broth demonstrated that CGP activity was constant over a pH range of 6-8 and was unaffected by the presence of 50% serum or 50% urine. The rate of killing of CGP, gentamicin, cefotaxime and ciprofloxacin was investigated in broth against log and stationary-phase cultures of Staphylococcus aureus and Escherichia coli. The most rapid rate of kill was seen with ciprofloxacin, while CGP exhibited a more rapid bactericidal effect than cefotaxime against Staph. aureus. The stability of CGP was studied at two concentrations in serum, broth and phosphate buffer at 4 degrees C, room temperature and 37 degrees C. In serum the half-life was 112 h at 4 degrees C, 35 h at room temperature and 11.4 h at 37 degrees C. Protein binding tested at concentrations of 5-100 mg/l was 2-6.3%.