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PubMed1972

Clinical and in vitro evaluation of cephapirin, a new cephalosporin antibiotic.

Cephapirin sodium, a cephalosporin for parenteral use, was evaluated in vitro and in 27 patients. Cephapirin had activity equivalent to cephalothin against 25 strains each of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus; 10 strains each of Diplococcus pneumoniae, Pseudomonas species, and Enterobacter species; and 8 strains of Proteus species other than P. mirabilis. All strains of S. aureus and D. pneumoniae and most strains of E. coli, K. pneumoniae, and Proteus species were inhibited by concentrations of cephapirin achieved in the serum. Of 27 patients (20 with pneumonia, 2 with S. aureus empyema, and 5 with miscellaneous infections), 25 responded to cephapirin therapy. The only major toxicity thought to be drug-related occurred in a patient who developed reversible bone marrow depression with leukopenia, neutropenia, and anemia. Although cephapirin was painful on intramuscular injection, phlebitis and pain were absent in patients treated intravenously. In a controlled comparison of intravenously administered cephalothin and cephapirin in four additional patients, the latter caused much less pain than the former and caused no phlebitis.

Acetamides↗

PubMed1972

Identification of cephalosporin-resistant Staphylococcus aureus with the disc diffusion method.

Methicillin-resistant strains of Staphylococcus aureus, in total 84, representing 16 laboratories in 8 different countries were all resistant to 32 mug of cephalothin per ml with the same typical heteroresistant pattern. With the disc diffusion method, they were easily detected when cephalexin discs were used. With cephalothin discs, on the other hand, 26 to 49% would have been falsely categorized as Group I or II after 24 hr. It is recommended that susceptibility testing of S. aureus to cephalosporins by using the paper disc method be performed with 30-mug cephalexin discs on Mueller-Hinton agar without blood. With an inoculum of 10(6) bacteria/ml, an incubation temperature of 30 C, and an incubation time of 24 hr, a zone of less than 10 mm indicates presumptive heteroresistance. This corresponds to the international recommendation with a minimal inhibitory concentration of 32 mug/ml as the upper limit of Group II.

Cephalosporins↗

PubMed1976

Comparison of the in vitro activity of several cephalosporin antibiotics against gram-negative and gram-positive bacteria resistant to cephaloridine.

The in vitro activity of each of two oral [cefatrizine (BL-S640), cephalexin] and three parenteral (cefamandole, cefazolin, cephapirin) cephalosporin antibiotics was compared with that of cephalothin against 168 clinical isolates of gram-negative and gram-positive bacteria selected as resistant to 20 mug of cephaloridine per ml on the basis of agar dilution susceptibility test data. Each of the five other cephalosporins inhibited a greater percentage of gram-negative bacillary isolates than did cephalothin or cephaloridine, with minimal inhibitory concentration values ranging 2- to 50-fold lower. Significant differences between minimal inhibitory concentrations of the compounds tested were also observed in tests against strains of Streptococcus faecalis and of methicillin-resistant Staphylococcus aureus. Potential advantages of including more than a single cephalosporin antibiotic in the panel of antibiotics used for routine susceptibility testing, suggested by these observations, are discussed.

Bacteria↗

PubMed1976

Comparison of the antibacterial activity of nine cephalosporins against Enterobacteriaceae and nonfermentative gram-negative bacilli.

The in vitro antibacterial activity of nine cephalosporins (cephalothin, cephaloridine, cephalexin, cefazolin, cefamandole, cefuroxime, cefatrizine, cefoxitin, and cefazaflur) was determined against 344 strains of Enterobacteriaceae and 99 nonfermentative gram-negative bacilli. Cefamandole, cefazaflur, and cefuroxime were the most active cephalosporins against the Enterobacteriaceae (with the exception of Serratia marcescens). However, cefoxitin was the only cephalosporin that inhibited all 30 S. marcescens strains in a concentration of 16 mug/ml and was by far the most active compound against selected cephalothin-resistant strains of Escherichia coli, Klebsiella, and Proteus mirabilis. Acinetobacter spp. were inhibited best by cefuroxime, but none of the cephalosporins had appreciable activity against the Pseudomonas spp.

Bacteria↗

PubMed1977

Evaluation of the Autobac 1 susceptibility testing system in a clinical diagnostic laboratory.

The Autobac 1 system was compared to the disk diffusion and agar dilution methods. Overall, there was good correlation; however, certain antibiotic/bacterial combinations gave unreliable results. In particular, unreliable results were obtained against staphylococci with penicillins, aerobic gram-negative rods with cephalothin, and enterococci with cephalothin and clindamycin.

Anti-Bacterial Agents↗

PubMed1977

Blood, brain, and cerebrospinal fluid concentrations of several antibiotics in rabbits with intact and inflamed meninges.

Because cerebrospinal fluid (CSF) antibiotic levels fail to predict either clinical success or relapse in the treatment of bacterial meningitis, we examined simultaneous antibiotic concentrations in the blood, brain, and CSF of control rabbits and of animals with experimental pneumococcal meningitis. Cefamandole pharmacokinetics were analyzed in detail and compared with those of cephalothin, ampicillin, penicillin G, and tobramycin. After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure. Cephalothin levels in the central nervous system remained undetectable in both control and infected animals during this time. Tobramycin concentrations were measurable in the CSF, but not in brain tissue in association with an inflammatory stimulus.

Animals↗

PubMed1978

Iodometric assay method for beta-lactamase with various beta-lactam antibiotics as substrates.

The rapid fixed-time assay for penicillinase was modified for measuring beta-lactamase activity with twelve substrates, i.e., benzylpenicillin, ampicillin, cloxacillin, methicillin, carbenicillin, cefazolin, cephalothin, cephaloglycin, cephalexin, cephalosporin C, 7-aminocephalosporanic acid, and cefoxitin. The method depends upon the reduction of iodine by the hydrolyzed substrate. Determined experimentally, 1 mol of hydrolyzed penicillins consumed 3.4 to 4.0 mol of iodine (I(2)). Iodine consumption of hydrolyzed cephalosporins varied widely from 1.7 for cephalothin to 3.7 for cefazolin. The method is useful for routine assay of beta-lactamase activity with various substrates.

Amidohydrolases↗

PubMed1978

Bactericidal activity of cephalosporins in an in vitro model simulating serum levels.

The bactericidal activity of cefazolin, cephaloridine, and cephalothin in a simulated intramuscular study (500 mg) and a simulated intravenous drip infusion study (2 g/2 h) is reported. In both model systems, the bactericidal activity of cefazolin surpassed that of cephalothin, and there were certain differences between cefazolin and cephaloridine in the simulated intramuscular study when human serum was used as a medium. In a routine reference static system, the drug levels were constant at the simulated peak level of each cephalosporin by both routes. In this system the three cephalosporins were equal in activity. In a third experiment, the effect of drug concentrations and exposure time on bactericidal activity of the cephalosporins was studied. The bactericidal activity of cephaloridine was the strongest of the three drugs when exposure time was 2 h and drug concentration was less than four times the minimal inhibitory concentration. At concentrations above four times the minimum inhibitory concentration, all three cephalosporins were equal in activity when the exposure time was 2 h.

Bacteria↗

PubMed1978

Susceptibility of 40 lactobacilli to six antimicrobial agents with broad gram-positive anaerobic spectra.

The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 40 lactobacillus strains were determined against six antibiotics with broad anaerobic spectra. Penicillin, ampicillin, clindamycin, and cephalothin were the most active inhibitory agents, with 95 to 100% of the strains inhibited at clinically achievable serum levels. However, despite the inhibitory efficacy of these four agents, only 5 to 22% of the isolates were killed at achievable concentrations. MBC:MIC ratios were high, ranging from 30:1 for cephalothin to 266:1 for ampicillin. Cefoxitin and metronidazole were generally ineffective against lactobacilli, with 87.5 to 100% of strains having unachievable MICs and/or MBCs. These findings may partially explain the clinical observations noting the inability to eradicate endocarditic lactobacillemias despite readily achievable MICs.

Anaerobiosis↗

PubMed1979

In vitro activity of mezlocillin and its related compounds against aerobic and anaerobic bacteria.

A total of 900 clinical isolates of aerobic (462 isolates) and anaerobic (438 isolates) bacteria were tested against mezlocillin in comparison with other penicillins, and the aerobes were also tested against cephalothin, cefoxitin, and cefamandole. Among penicillins, mezlocillin was the most effective against Escherichia coli, Klebsiella pneumoniae, Salmonella species, Pseudomonas aeruginosa, and Bacteroides fragilis. Mezlocillin was more effective than cephalothin against Klebsiella pneumoniae.

Aerobiosis↗

PubMed1979

Ceforanide: in vitro and clinical evaluation.

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at </=12.5 mug/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 mug/ml and that at 12 h was 4.7 mug/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to Staphylococcus aureus, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.

Adult↗

PubMed1979

In vitro activity of LY127935.

LY127935 is a unique new beta-lactam antibiotic. Its activity against 536 clinical isolates was studied by using microdilution methods of susceptibility testing and compared with the activities of cefamandole, cefoxitin, and cephalothin. The lowest concentrations required to inhibit at least 90% of strains tested (MIC(90)s) of LY127935 for Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae ranged from 2 to 8 mug/ml. The MIC(90)s for other staphylococci and streptococci were higher. The MIC(90)s for Enterobacteriaceae and Pseudomonas species ranged from 0.12 to 8 mug/ml and 8 to >32 mug/ml, respectively. The MIC(90)s for anaerobes ranged from 2 to >32 mug/ml. As determined by MIC(90)s, LY127935 was consistently the least active antibiotic against facultatively anaerobic gram-positive cocci and the most active against aerobic and facultatively anaerobic gram-negative bacilli. Its position with respect to activity against anaerobes varied from being the most active against Bacteroides fragilis and Clostridium perfringens to the least active against anaerobic cocci. In a population of multidrug-resistant isolates, concentrations of 8 mug or less of LY127935 per ml inhibited 82% of Enterobacteriaceae; concentrations of 32 mug or less per ml inhibited 100% of Enterobacteriaceae and 40% of P. aeruginosa. Increasing the inoculum size by 100-fold did not increase the minimal inhibitory concentrations of LY127935 or cefoxitin but did increase minimal inhibitory concentrations of cefamandole and cephalothin for some Enterobacteriaceae. All four drugs were bactericidal; minimal bactericidal concentrations were the same or one concentration higher than minimal inhibitory concentrations for 91 to 96% of strains tested. The broad spectrum and marked in vitro activity of LY127935 make it a promising new antibiotic.

Aerobiosis↗

PubMed1980

Comparative activities of the oxa-beta-lactam LY127935, cefotaxime, cefoperazone, cefamandole, and ticarcillin against multiply resistant gram-negative bacilli.

A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephalothin, chloramphenicol, and ampicillin. Their susceptibility to three new broad-spectrum beta-lactams, LY127935 (a 1-oxa-beta-lactam), cefotaxime (HR 756), and cefoperazone (T 1551), was compared with the susceptibility of random strains of nine species of aerobic gram-negative bacilli collected in the same hospital in 1979. Susceptibility to cefamandole and ticarcillin was also determined. Strains of staphylococci and streptococci from that hospital and two nearby city-county hospitals were also compared for the three new cephalosporins and other effective antibiotics. The agar dilution method was used to measure the minimum inhibitory concentration for each antibiotic. The multiply resistant strains (minimum inhibitory concentration for gentamicin >/= 8 mug/ml) usually were as susceptible to the three new broad-spectrum beta-lactams as were non-multiply resistant strains. Both Klebsiella pneumoniae and Serratia marcescens, including multiply resistant and non-multiply resistant strains, were most susceptible to the 1-oxa-beta-lactam LY127935 and cefotaxime. P. aeruginosa (both multiply resistant and non-multiply resistant strains) were most susceptible to cefoperazone. All three new beta-lactams were active against non-multiply resistant strains of Escherichia coli, Enterobacter spp., Proteus spp., and Citrobacter spp. Providencia stuartii were most susceptible to cefotaxime and the 1-oxa-beta-lactam LY127935. The three new beta-lactams were all less active against staphylococci (especially methicillin-resistant Staphylococcus aureus) than cephalothin. Streptococcus pyogenes and S. pneumoniae were very susceptible to cefotaxime and cefoperazone, though less susceptible to LY127935. None of the three new beta-lactams was active against S. faecalis. All were very active against both penicillinase-positive and -negative strains of Neisseria gonorrhoeae.

Bacteria↗

PubMed1980

Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing.

Tested against 9,412 recent clinical isolates, cefotaxime exhibited 8 to 64 times greater activity against the Enterobacteriaceae than did cephalothin and two to four times greater activity against Pseudomonas aeruginosa, but only one-half to one-eighth the activity of cephalothin against staphylococci. Using 420 different clinical isolates, but with comparable minimal inhibitory concentration (MIC) distributions, disk diffusion-MIC regression analyses were performed, using 5- and 30-micrograms cefotaxime disks. Cefotaxime MIC susceptible and resistant breakpoints of less than or equal to 8 and greater than 32 micrograms/ml are tentatively proposed. Based on the MIC breakpoints, the data showed the best discrimination among the three susceptibility categories (susceptible, indeterminate, and resistant) when the 30-micrograms cefotaxime disk was used. The zone diameter breakpoints as determined by the error rate-bounded method and regression analysis were greater than or equal to 23 mm for susceptible, 15 to 22 mm for indeterminate, and less than or equal to 14 mm for resistant.

Bacteria↗

PubMed1980

Comparative in vitro appraisal of piperacillin, including its activity against Salmonella typhi.

Piperacillin was evaluated in vitro against 711 clinical isolates of aerobic and anerobic gram-positive and gram-negative bacteria, including 76 isolates of Salmonella typhi. Piperacillin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were compared with those of a range of beta-lactam, aminoglycoside, and other antimicrobial agents, and inoculum size effects were considered. The relationship between dilution and disk diffusion tests was studied by regression analysis. In addition, piperacillin was assessed in combination with aminoglycoside and other beta-lactam drugs. This investigation has confirmed the activity of piperacillin against a broad range of bacteria, including Pseudomonas, Enterobacteriaceae, Neisseria, beta-lactamase-negative Haemophilus influenzae, and Staphylococcus aureus as well as enterococci, Bacteroides fragilis, and other anaerobes. All strains of Pseudomonas aeruginosa were inhibited by </=32 mug/ml or less, demonstrating again the potential usefulness of piperacillin in the treatment of pseudomonal infections. S. typhi proved susceptible to piperacillin, all isolates being inhibited by 1 mug/ml. Inoculum size experiments showed that inocula of 10(8) CFU resulted in MICs and MBCs appreciably higher than those resulting from inocula of 10(6) CFU, and inocula of 10(2) CFU resulted in MICs and MBCs appreciably lower than those resulting from inocula of 10(4) CFU. Piperacillin was active against all gentamicin-resistant pseudomonads tested, but not against gentamicin-resistant klebsiellas and enterobacters. Combinations of piperacillin with tobramycin and amikacin were consistently synergistic against Pseudomonas and Serratia isolates. Less consistent results were shown when piperacillin was combined with aminoglycosides or cephalothin against Klebsiella and indole-positive Proteus isolates, although synergy was observed in most cases. Occasional antagonistic reactions were encountered with piperacillin-cephalothin or piperacillin-tobramycin combinations against the latter isolates.

Anti-Bacterial Agents↗

PubMed1980

Differences among Providencia species in their in vitro susceptibilities to five antibiotics.

Significant differences among the three Providencia species (P. alcalifaciens, P. stuartii, and P. rettgeri) in antimicrobial susceptibilities to five antibiotics were shown. P. stuartii was the most resistant of the three species, and P. alcalifaciens was the most susceptible. P. rettgeri was similar to P. stuartii in susceptibilities to cefoxitin, cephalothin, and cefamandole but differed in showing greater susceptibilities to tobramycin and gentamicin. Cefoxitin (16 micrograms/ml) and cefamandole (16 micrograms/ml) inhibited a greater proportion of P. stuartii isolates than did cephalothin, tobramycin, or gentamicin. The susceptibilities of urea-positive isolates of P. stuartii resembled more closely the susceptibilities of urea-negative isolates of this species than those of P. rettgeri isolates, a finding consistent with the recent recommendation for transferring such urea-positive strains to P. stuartii. Among P. stuartii isolates, marked resistance to cefoxitin accompanied by susceptibility to cefamandole was predominantly restricted to isolates of one serotype (O55). The use of isolates that had been serotyped and classified according to recent proposals for taxonomic changes in the Proteeae provided for clearer demonstration of species differences in susceptibility.

Anti-Bacterial Agents↗

PubMed1980

Antimicrobial susceptibility of Campylobacter jejuni and Campylobacter fetus subsp. fetus to eight cephalosporins with special reference to species differentiation.

Agar dilution antimicrobial susceptibility testing showed that Campylobacter jejuni was significantly more resistant than Campylobacter fetus subsp. fetus (intestinalis) to cephalosporin C, cephaloridine, cephalothin, cefazolin, and cefamandole. No species differences in susceptibility were noted with cephalexin, cefotaxime, and cefoxitin. Rapid species differentiation on the basis of an antibiogram could be achieved with the disk diffusion method. C jejuni failed to produce a zone of inhibition around a 30-microgram cephalothin disk but produced a significant zone around a 30-microgram nalidixic acid disk. C. fetus subsp. fetus (intestinalis) produced exactly the reverse pattern.

Campylobacter↗

PubMed1981

Susceptibility of anaerobic bacteria to nine antimicrobial agents and demonstration of decreased susceptibility of Clostridium perfringens to penicillin.

The activity of moxalactam, cefoxitin, cephalothin, cefamandole, chloramphenicol, clindamycin, metronidazole, and ticarcillin was determined against 344 isolates of anaerobic bacteria. The activity of penicillin G was determined as well for 234 isolates not of the Bacteroides fragilis group. Moxalactam was more active than cephalothin and cefamandole and slightly less active than cefoxitin. Metronidazole was the most active antimicrobial agent against the B. fragilis group, whereas chloramphenicol was most active overall. Clostridium species were the most resistant group of organisms tested. Relatively high concentrations of penicillin were required to inhibit the C. perfringens strains: 80% at 0.5 U/ml and 100% at 16 U/ml. Our study demonstrates the need for periodic anaerobe susceptibility testing in order to better guide empiric antibiotic therapy.

Anaerobiosis↗