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Comparative beta-lactamase resistance and antistaphylococcal activities of parenterally and orally administered cephalosporins.

Two parenterally administered cephalosporins (cephalothin and cephapirin) and four orally administered cephalosporins (cephalexin, cephradine, cefatrizine, and cefaclor) were investigated by use of 29 beta-lactamase-producing strains of Staphylococcus aureus for determination of their relative rates of hydrolysis (RH) by beta-lactamase (RH of penicillin G =100) and their antistaphylococcal activities. Cephalothin (RH less than 0.01) and cephapirin (RH = 0.1) were relatively stable in the presence of staphylococcal beta-lactamase. Cephalexin and cephradine (RH of each = 0.3) were less stable than cephalothin and cephapirin but more stable than cefatrizine (RH = 1.4) and cefaclor (RH = 3.4). Agents that were more resistant to hydrolysis were affected less by the size of the inoculum when tested against large ;(10(7)) and small (10(3)) inocula of beta-lactamase-producing staphylococci than those that were hydrolyzed rapidly. Cephalothin and cephapirin were four to eight times more active than the orally administered cephalosporins against 10(3) staphylococci. Cephalosporins that are relatively stable in the presence of staphylococcal bata-lactamase may be preferable to less stable ones for treatment of serious infections due to beta-lactamase-producing staphylococci.

Administration, Oral↗

Simultaneous determination of different antibiotic residues in bovine and in porcine kidneys by solid-phase fluorescence immunoassay.

Parallux, a solid-phase fluorescence immunoassay (SPFIA) developed for antibiotic residue detection in milk, was used for analysis of bovine and porcine kidney tissue. Four tetracyclines, 2 broad-spectrum cephalosporins, 3 beta-lactam antibiotics, and cephapirin were detected in one run after minimal sample preparation. This commercially available test system is designed as cartridges, each with a combination of 1-4 tests. One cartridge can be used to detect 4 analytes in the same sample, or 1 or 2 analytes in different samples. The cartridge with the combination tetracyclines-ceftiofur-penicillin-cephapirin was selected because tetracyclines, beta-lactam antibiotics as well as cephalosporins, are registered for oral or parenteral use in bovines and pigs in Europe. The test is qualitative and is recommended only for screening. Tetracycline, oxytetracycline, chlortetracycline, and doxycycline were easily detected at 300 ppb with the tetracyclines channel; ceftiofur at 1000 ppb and cefquinome at 200 ppb with the ceftiofur channel; penicillin G, ampicillin, and amoxicillin at 50 ppb with the penicillin channel; and cephapirin at 100 ppb with the cephapirin channel. These levels are equal to or lower than the corresponding maximal residue limits in kidney tissue. Cephalexin was not detected. The SPFIA test can be used as an alternative to classical inhibition tests and for post-screening inhibitor- positive kidneys, because it detects 3 specific groups of antibiotics, which enables selection of specific confirmatory methods for identification and quantification.

Animals↗

Pharmacokinetics of five cephalosporins in healthy male volunteers.

This paper deals with data on the pharmacokinetics of cephazolin, cephalothin, cephapirin, cephaloridine and cephradine after i.m. injection of a single dose of 0.5 g in healthy male volunteers. Peak serum concentrations occurred 45 min after the administration and were 31.52 microgram/ml for cephazolin, 17.32 microgram/ml for cephaloridine, 13.98 microgram/ml for cephapirin, 9.51 microgram/ml for cephradine and 8.60 microgram/ml for cephalothin. The average half-lives were found to be 2.07, 1.80, 0.98, 1.24 and 0.97 h, respectively. The percentage of protein binding was found to be 82 for cephazolin, 59 for cephalothin, 51 for cephapirin, 31 for cephaloridine and only 10 for cephradine, half an hour after drug administration. The total urine recovery of the above cephalosporins, within 24 h, was 91.9% for cephradine, 81.9% for cephaloridine, 73.3% for cephazolin, 69.5% for cephapirin and 51.2% for cephalothin.

Adult↗

Savings achieved through cephalosporin surveillance.

The process by which a 427-bed, acute-care teaching hospital reduced the cost of cephalosporin therapy is described. During a nine-month surveillance period, cefazolin prescribing patterns were monitored. Of the 674 patients who received cefazolin, 640 (92%) received dosages greater than those recommended in the literature. Attempts were made to alter inappropriate prescribing through pharmacist-physician consultation and through contact with the medical service representative of the company which supplied cefazolin. Because these efforts failed, the pharmacy and therapeutics committee decided to delete cefazolin from the formulary. Cephalothin and cephapirin were found to be clinically similar; therefore, the committee recommended that the less expensive cephapirin be dispensed whenever a parenteral cephalosporin was ordered. Prior to the switch to cephapirin, cefazolin accounted for 49% of all parenteral cephalosporin use and 62% of the cephalosporin cost. Cephalothin and cefazolin were 30% and 88%, respectively, more expensive than cephapirin. In the first year after the switch, the hospital saved $33,196 (28.8% of the previous year's total expenditures for cephalosporins).

Cephalosporins↗

Interleukin 2 treatment of Staphylococcus aureus mastitis.

A study was conducted in dairy cows to evaluate the efficacy of recombinant bovine interleukin 2 (rBoIL-2) as an adjunct to antibiotic therapy in Staphylococcus aureus mastitis. In normal, non-mastitic cows, intramammary infusion of rBoIL-2 caused a tenfold increase in somatic cell counts (SCC) in milk. Co-administration of 2 mg of rBoIL-2 and sodium cephapirin in cows with established S. aureus mastitis decreased SCC and shedding of S. aureus compared with values from cows that were given only sodium cephapirin or 10 mg rBoIL-2 with sodium cephapirin. Cows in the 2 mg rBoIL-2 group cleared the infection earlier and at 2 weeks after treatment had not relapsed with staphylococcal mastitis. These data suggest that rBoIL-2 may be useful as an immunotherapeutic agent in controlling mastitis.

Animals↗

The effect of treatment of clinical endometritis on reproductive performance in dairy cows.

The objective of this field trial was to compare the effect of intrauterine (i.u.) antibiotic or intramuscular (i.m.) prostaglandin F2 alpha (PGF2 alpha) on time to pregnancy in dairy cows diagnosed with clinical endometritis between 20 and 33 days in milk (DIM). The case definition of endometritis was the presence of purulent uterine discharge or cervical diameter > 7.5 cm, or the presence of muco-purulent discharge after 26 DIM. There were 316 cows with endometritis from 27 farms assigned randomly within herd to receive 500 mg of cephapirin benzathine intrauterine (i.u.), 500 micrograms of cloprostenol i.m., or no treatment. The rate of resolution of clinical signs 14 d after treatment was 77% and was not affected by treatment. Reproductive performance was monitored for a minimum of 7 mo after treatment. Survival analysis (multivariable proportional hazards regression) was used to measure the effect of treatment on time to pregnancy. There was no benefit of treatment of endometritis before 4 wk postpartum. Administration of PGF2 alpha between 20 and 26 DIM to cows with endometritis that did not have a palpable corpus luteum was associated with a significant reduction in pregnancy rate. Between 27 and 33 DIM, cows with endometritis treated with cephapirin i.u. had a significantly shorter time to pregnancy than untreated cows (hazard ratio = 1.63). In this time period, there was no difference in pregnancy rate between PGF2 alpha and untreated cows, but the difference in pregnancy rate between cows treated with cephapirin i.u. and with PGF2 alpha was not statistically significant. Treatment of postpartum endometritis should be reserved for cases diagnosed after 26 DIM, based on criteria that are associated with subsequent pregnancy rate.

Animals↗

Postthaw survival and fertility of frozen bull spermatozoa treated with antibiotics and detergent.

Five factorial experiments were conducted, each with 10 bulls, three extenders, and six antibiotic treatments to determine safe levels of new antibiotics to add to bull spermatozoa. Dicloxacillin, cephapirin, ceforanide, gentamicin, and minocin were added at five concentrations to whole milk, egg yolk-Tris, and egg yolk-Tris detergent (sodium triethanolamine lauryl sulfate) extenders with penicillin and streptomycin as a control. Semen was extended to 20 X 10(6) sperm/ml, packaged in .5-ml straws, frozen and stored in liquid nitrogen, and thawed at 35 degrees C for 30 s. Two people assessed postthaw percentage of motile spermatozoa from two straws per treatment. Bulls and extenders always affected sperm motility significantly. Percentage of intact acrosomes of spermatozoa was assessed in selected treatments but did not differ in any experiment. Sodium triethanolamine lauryl sulfate tended to improve cryopreservation of spermatozoa. Percentage of motile spermatozoa in milk declined when concentrations of dicloxacillin exceeded 200 micrograms/ml or when gentamicin, as Gentocin, exceeded 500 micrograms/ml. Minocin was toxic at all levels tested in egg yolk and was nontoxic to sperm in milk extender at concentrations less than or equal to 100 micrograms/ml. Cephapirin and ceforanide were innocuous at all concentrations tested (200 to 2000 micrograms/ml). Fertility with cephapirin (500 micrograms/ml) added to an extender containing control antibiotics resulted in a 56-d nonreturn rate of 75.5 versus 72.1% for the control.

Animals↗

Prevalence of minor udder pathogens after intramammary dry treatment.

A total of 156 dairy cows was randomly assigned to one of four groups at drying off over an 18-mo period: untreated control or intramammary treatment of each mammary quarter with either 400 mg novobiocin, 300 mg cephapirin, or 1 g dihydrostreptomycin with 1 million units penicillin. Quarter foremilk samples were aseptically collected from each cow within 1 mo of drying off and within 1 mo after parturition for bacteriological analysis. Prior to drying off, 28.7% of quarters were positive of which 46.7% were Corynebacterium bovis and 45.5% were coagulase-negative staphylococci. Reductions in infection prevalence from drying off to postpartum samplings for control, novobiocin, cephapirin, and streptomycin-penicillin groups were 13.6, 60.5, 74.4, and 35.3% of quarters. Recovery rates for C. bovis infections were 47.6, 100, 100, and 94.1%; for coagulase-negative staphylococci infections they were 72.7, 86.4, 80.0, and 100%. The cephapirin group showed the lowest new infection rate (1.3%) with coagulase-negative staphylococci compared with control (6.9%). There were no significant differences in lactation milk production among groups following dry period therapy. Results suggest that dry treatment reduces the prevalence of infections by the minor mastitis pathogens.

Animals↗

Systemic dry cow therapy--a preliminary report.

Efficacy of three different treatment regimens in the elimination and prevention of Staphylococcus aureus intramammary infection was studied in 106 dry cow periods. At drying off, norfloxacin nicotinate was given subcutaneously to 44 cows at 10 mg/kg, oxytetracycline-HCl was administered intramuscularly to 18 cows at 20 mg/kg, 500 mg cephapirin benzathine were infused into each udder quarter of 21 cows, and a group of 23 cows served as an untreated control. Number of existing Staphylococcus aureus intramammary infections was reduced only in the norfloxacin nicotinate treatment group. New infection rate appeared lower in the two systemic treatment groups. The percentage of infected quarters remained the same throughout the dry period in the norfloxacin treatment group but number of infected quarters increased by 33 to 85% (significant in the cephapirin group) in the other groups. Minimal inhibitory concentration of the drugs for 57 S. aureus isolates was determined. Isolates were sensitive to norfloxacin and cephapirin and moderately sensitive to oxytetracycline. Results suggest that systemic dry cow therapy using norfloxacin nicotinate, which possesses large distribution volume, long half-life, and is highly active against the pathogen involved, was more effective than the other treatments.

Animals↗

Determination of milk and mammary tissue concentrations of ceftiofur after intramammary and intramuscular therapy.

Twenty-five Staphylococcus aureus strains isolated from bovine mastitis were tested for their susceptibility to ceftiofur. Zone diameter for 30 micrograms disks averaged 39 mm, and minimum inhibitory concentrations ranged from .5 to 1 microgram/ml. Tissue and milk concentrations were determined from biopsy and quarter milk samples collected from eight cows treated with either intramammary infusion of 100 or 200 mg of ceftiofur, one or two intramuscular injections of 500 mg of ceftiofur, or combination therapy of intramammary infusion coupled with intramuscular injection. Three additional cows received two intramammary infusions of 200 mg of cephapirin at 24-h intervals. Intramuscular injections of ceftiofur resulted in tissue and milk concentrations below detectable limits. Staphylococcus aureus was not eliminated from infected mammary glands by infusion of 100 mg of ceftiofur or by injection of 500 mg of ceftiofur by 48 h after treatment. Combination therapy of 100 mg of ceftiofur infused and 500 mg injected reduced S. aureus numbers in milk and tissue markedly, as did infusion of 200 mg of ceftiofur. Cows receiving intramammary infusion of 200 mg of ceftiofur (two doses at 24-h intervals) had highest concentrations in milk (450 micrograms/ml at 4 and 6 h) and in tissue (.08 microgram/mg at 30 h). These concentrations are similar to those obtained with two 200-mg doses of cephapirin at 24-h intervals. Histologic analysis of mammary parenchymal tissues showed that combination therapy resulted in higher percentages of alveolar luminal area and lower percentages of interalveolar stroma compared with infusion or injection alone. Histology of quarters receiving combination therapy was not different from that of quarters receiving cephapirin infusion alone.

Animals↗

[Antibiotic levels in blood serum and mandibular bone in rats with and without phenylbutazone administration].

Antibiotics' level was estimated in mandible and serum of wistar albino rats with and without co-administration of phenylbutazone, 5 groups of animals were used. The animals of group A were injected with 1 g/kg ampicillin and these of group B 1g/kg ampicillin and 100 mg/kg phenylbutazone im. To the animals of group C cephapirin was given 1 g/kg and these of group D 1g/kg cephapirin with 100 mg/kg phenylbutazone. The animals of group E were injected only with phenylbutazone. All the drugs, were given at a single dose. The level of antibiotics was estimated in serum and in mandible with the method of minimal inhibitory concentration (MIC). An increase of the levels of antibiotics (ampicillin, cephapirin) was observed in those groups (B, D) to the animals of which phenylbutazone was given (together with antibiotics), compared with the groups (A, C) which had received antibiotics alone.

Ampicillin↗

Particulate matter in four reconstituted cephalosporin injections.

The amount and size of particulate contamination in three commercially available cephalosporin injections and a new product, anophilized cephalothin sodium injection, were studied. Particles in reconstituted cephalothin sodium (commercially available and anophilized), cephapirin sodium, and cephradine injections were counted using two methods: (1) modified USP membrane-filtration technique and (2) Elzone computerized particle analyzer. The amount of particulate contamination in the ranges of 10-24 and greater than or equal to 25 microns was determined by both methods. In the 10-24-microns range, the cephalothin, cephapirin, and cephradine products had significantly greater particle counts than the anophilized cephalothin product. The greater than or equal to 25-microns particle counts showed that the cephapirin and cephradine products had particle counts greater than the anophilized cephalothin product, while total particle counts showed the same results as the 10-24-microns particle counts. A comparison of counting methods showed that the only significant difference between the number of particulates obtained using the modified USP and Elzone computer methods was with the cephalothin product. Anophilized cephalothin sodium injection has significantly fewer particles in the size ranges studied. No conclusion could be reached as to the more accurate method for counting particles.

Cephalosporins↗

Screening and mass spectral confirmation of beta-lactam antibiotic residues in milk using LC-MS/MS.

Milk is typically screened for beta-lactam antibiotics by nonspecific methods. Although these methods are rapid and sensitive, they are not quantitative and can yield false positive findings. A sensitive and specific method for the quantitation and mass spectral confirmation of five beta-lactam and two cephalosporin antibiotics commonly or potentially used in the dairy industry is described using high-performance liquid chromatography with tandem mass spectrometry. The antibiotics studied were ampicillin, amoxicillin, penicillin G, penicillin V, cloxacillin, cephapirin, and ceftiofur. The antibiotics were extracted from milk with acetonitrile, followed by reversed-phase column cleanup. The extract was analyzed by liquid chromatography coupled with a mass spectrometer, using a water/methanol gradient containing 1% acetic acid on a C-18 reversed-phase column. Determination was by positive ion electrospray ionization and ion trap tandem mass spectrometry. Quantitation was based on the most abundant product ions from fragmentation of the protonated ion for amoxicillin, cephapirin, ampicillin, and ceftiofur and on the fragmentation of the sodium adduct for penicillin G, penicillin V, and cloxacillin. The method was validated at the U.S. FDA tolerance or safe level and at 5 or 2.5 ng/mL for these compounds in bovine milk. Theoretical method detection limits in milk based on a 10:1 signal to noise ratio were 0.2 ng/mL (ampicillin), 0.4 ng/mL (ceftiofur), 0.8 ng/mL (cephapirin), 1 ng/mL (amoxicillin and penicillin G), and 2 ng/mL (cloxacillin and penicillin V) using a nominal sample size of 5 mL.

Animals↗

Effect of intrauterine antibiotic treatment on reproductive performance of dairy cows following periparturient disease.

AIMS: To quantify the effect of treating lactating dairy cows that had histories of periparturient disorders or disease with a single intrauterine infusion of 0.5 g cephapirin, 3-6 weeks prior to the start of the seasonal breeding period. METHODS: Cows (n=690) from spring-calving dairy herds (n=22) were enrolled in a prospective case-control study if they had a history of dystocia, a dead calf at calving or within 24 h of calving, retained foetal membranes (RFM), metabolic disease, twins or a vulval discharge 13 days postpartum. Cows were blocked by age, periparturient condition and calving date, and randomly assigned to be either treated with 0.5 g of cephapirin by intrauterine infusion, or left as untreated controls. Treatment occurred 24-42 days before the planned start of mating (PSM) within each herd. In addition, the reproductive tracts of 91 cows from 4 herds were examined using a vaginal speculum and rectal palpation and cervical-os discharge was scored on a scale from 0 (nil) to 3 (purulent). RESULTS: Overall, more treated cows were retained in the trial herds until pregnancy testing than control cows (p0.05). Average 28-day submission rate was higher (93.1% vs 87.1%; p0.05) and PSM-to-first-service interval was shorter (9+/-1 vs 11+/-1 days; p0.05) in treated than control cows. The percentage of cows not pregnant at the end of the mating period was not affected by treatment overall. However, amongst cows diagnosed with RFM, a dead calf, or vulval discharge, pregnancy rates 28 and 56 days after PSM were higher for treated than control cows (p0.05). Cows with a purulent cervical-os discharge had lower 28-day submission rates (p0.01), lower 28-day pregnancy rates (p0.05) and higher non-pregnant rates at the end of mating than cows with nil or mucoid cervical-os discharges. CONCLUSIONS: Intrauterine treatment with 0.5 g cephapirin improved reproductive performance of dairy cattle, especially those that had a history of RFM, a calf dead at calving or within 24 h of calving, or a vulval discharge.

Journal Article↗

Effect of selected antibiotics on Staphylococcus aureus present in milk from infected mammary glands.

Milk from a mammary gland infected with Staphylococcus aureus Newbould 305 was collected and dispensed into sterile tubes. Selected antibiotics were added at 2, 4, or 32 times the MIC, and the percentage survival of S. aureus at various times through 24 h after addition of each antibiotic was determined. Percentage survival of the same S. aureus strain grown in vitro and added to 1) Mueller-Hinton broth and 2) ultrahigh temperature pasteurized milk with the same concentration of antibiotics was also determined. Percentage survival observed after 24 h in milk from the infected quarter at 2, 4, and 32 times MIC, respectively, were: penicillin: 12, 9.4, and 13%; cephapirin 43, 50, and 30%; erythromycin: 120, 95, and 82%; pirlimycin: > 1000, 148, and 38%; tilmicosin: > 1000, > 1000, and 9%; ciprofloxacin: 458, 6, and 3%; norfloxacin: 40, 10, and < 1%; rifampicin: < 1, < 1, and < 1%; and novobiocin: 20, 41, and 5%. By comparison, percentage survival observed after 24 h for in vitro grown S. aureus tested in Mueller-Hinton broth at 2, 4, and 32 times MIC, respectively, were < 1% for penicillin, cephapirin, pirlimycin, ciprofloxacin, norfloxacin, and rifampicin, and < 10% for erythromycin, novobiocin, and tilmicosin. UHT milk had minimal effect on percentage survival compared to Mueller-Hinton broth for S. aureus 305 when tested against penicillin or cephapirin. Increased survival was noted in UHT milk for erythromycin, pirlimycin, and tilmicosin at all antibiotic concentrations and for ciprofloxacin, norfloxacin, rifampicin, and novobiocin at 2 times the MIC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Susceptibility of Rhodobacter sphaeroides to beta-lactam antibiotics: isolation and characterization of a periplasmic beta-lactamase (cephalosporinase).

Thirteen strains of the gram-negative, facultative phototrophic bacterium Rhodobacter sphaeroides were examined fro susceptibility to beta-lactam antibiotics. All strains were sensitive to the semisynthetic penicillins ampicillin, carbenicillin, oxacillin, cloxacillin, and methicillin, but 10 of the 13 strains were resistant to penicillin G, as well as a number of cephalosporins, such as cephalothin, cephapirin, and cephalosporin C. A beta-lactamase (EC 3.5.2.6) with strong cephalosporinase activity was detected in all of the resistant strains of R. sphaeroides. With strain Y-1 as a model, it was shown that the beta-lactamase was inducible by penicillin G, cephalosporin C, cephalothin, and to some minor extent, cephapirin. The beta-lactamase was located in the periplasmic space, from which it could be extracted by osmotic shock disruption. By using this fraction, the beta-lactamase was purified 34-fold to homogeneity by steps involving batch adsorption to and elution from DEAE-Sephadex A50, chromatography on Q-Sepharose, and preparative polyacrylamide gel electrophoresis. The molecular masses of the native and denatured enzymes were determined to be 38.5 kilodaltons by gel filtration and 40.5 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively, indicating a monomeric structure. The isoelectric point was estimated to be at pH 4.3. In Tris hydrochloride buffer, optimum enzyme activity was measured at pH 8.5. The beta-lactamase showed high activity in the presence of the substrates cephalothin, cephapirin, cephalosporin C, and penicillin G, for which the apparent Km values were 144, 100, 65, and 110 microM, respectively. Cephalexin, cepharidine, and cephaloridine were poor substrates. The beta-lactamase was strongly inhibited by cloxacillin and oxacillin but only slightly inhibited by phenylmethylsulfonyl fluoride or thiol reagents such as iodoacetate and p-chloromercuribenzoate.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of microorganisms isolated from the mammary glands of dairy heifers.

Minimum inhibitory concentrations were determined with 1494 microorganisms isolated from the mammary glands of dairy heifers. The antimicrobial agents tested were penicillin, cloxacillin, cephapirin, ceftiofur, novobiocin, enrofloxacin, erythromycin, and pirlimycin. All minimum inhibitory concentrations were expressed as micrograms per milliliter. The isolates tested included 135 Staphylococcus aureus, 1222 Staphylococcus sp., 42 Streptococcus sp., 15 Enterococcus sp., 60 enteric species, and 20 miscellaneous organisms. The minimum inhibitory concentrations for 90% of isolates for the various antimicrobial agents with Staph. aureus were as follows: penicillin, .13; cloxacillin, .5; cephapirin, .5; ceftiofur, 1; novobiocin, .5; enrofloxacin, .5; erythromycin, .5, and pirlimycin, .5. In comparison, the minimum inhibitory concentrations for 90% of isolates for the Staphylococcus sp. were 1, 1, .5, 1, .5, .5, 1, and .5 for penicillin, cloxacillin, cephapirin, ceftiofur, novobiocin, enrofloxacin, erythromycin, and pirlimycin, respectively. The minimum inhibitory concentrations for 90% of isolates for the Streptococcus sp. were 2, 32, 2, 2, 8, 1, 64, and 32 for the respective antimicrobial agents; the minimum inhibitory concentrations for 90% of isolates were 4, 64, 32, 64, 4, 1, 4, and 4 for the enterococci. Against the Gram-negative enteric bacilli, only ceftiofur and enrofloxacin were active; minimum inhibitory concentrations for 90% of isolates were 1 microgram/ml for ceftiofur and .25 microgram/ml for enrofloxacin. Results indicated that the majority of staphylococcal strains were susceptible to the antimicrobial agents tested but that antimicrobial susceptibility varied for Streptococcus sp. Compounds currently available in intramammary infusion products demonstrated poor activity against the enteric organisms.

Animals↗

Comparative in vitro activity of cephalosporins.

The in vitro activity of cephalexin, cephaloridine, cephalothin, cephapirin, cefoxitin, cephamycin C, cepharadine and cefazolin was determined against 443 isolates of bacteria. At a concentration of 12.5 mug/ml, all of the cephalosporins inhibited more than 60% of the isolates of Klebsiella pneumoniae. At the same concentration, cephalexin, cephaloridine, cephalothin, cephapirin, cephamycin C and cefazolin inhibited more than 90% of isolates of proteus mirabilis. All of the cephalosporins except cephalothin and cephapirin inhibited over 60% of isolates of Escherichia coli at a concentration of 12.5 mug/ml. Cefoxitin was the most active cephalosporin against gram-negative bacilli. There was substantial differences in the activity of cephalosporins against gram-positive cocci. Cephaloridine was the most active cephalosporin against these organisms. There was considerable fluctuation in the proportion of isolates of gram-negative bacilli susceptible to these cephalosporins from year to year, but there was no evidence to suggest that the number of resistant isolates was increasing.

Cephalosporins↗