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PubMed1988

Comparative toxicities of cephalosporin antibiotics in a rabbit kidney cell line (LLC-RK1).

The rabbit kidney cell line LLC-RK1 was tested for its ability to discriminate the toxicities of six cephalosporin antibiotics according to their in vivo nephrotoxic potentials in rabbits. With the exception of cephalothin, which was markedly toxic to kidney cells in vitro, a good correlation between in vitro toxicity and in vivo nephrotoxicity was obtained, yielding the following toxicity rank order: ceftazidime less than cefazolin approximately cefoperazone less than cephaloglycin approximately cephaloridine. The addition of a kidney microsomal S9 fraction to the cell cultures desacetylated cephalothin as occurs in vivo and detoxified this antibiotic, providing it with the proper toxicity relative to the other cephalosporins. When compared with parent structures, desacetylated derivatives of other cephalosporins such as cephapirin were similarly found to be less toxic to LLC-RK1 cells. The acetylated cephalosporin cephaloglycin was not detoxified by the kidney S9 fraction and was desacetylated three to four times slower than cephalothin by renal esterases. Thus, the rate and extent of desacetylation of cephalosporins may play a role in their in vivo nephrotoxic potential. Our results further suggest that LLC-RK1 cells will provide a useful model for evaluating the potential nephrotoxicity of new cephalosporin antibiotics before in vivo studies.

Animals↗
PubMed1990

Comparison of in vitro antimicrobial susceptibilities of Mycobacterium avium-M. intracellulare strains from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and animal sources.

Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M. intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals. Against the isolates from humans without AIDS, the quinolone compounds difloxacin and A-56620 were found to be the most effective, each inhibiting 50% of strains at a concentration of 2 micrograms/ml. The remaining antimicrobial agents had MICs for 50% of strains tested of at least 32 micrograms/ml. Statistically significant differences were observed in the antibiogram patterns among the M. avium-M. intracellulare strains from each of the three sources.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Characterization of four beta-lactamases produced by Staphylococcus aureus.

Staphylococcus aureus produces four types of beta-lactamase (A, B, C, and D). To investigate the effect of specific beta-lactamase type upon staphylococcal resistance, each beta-lactamase was purified to homogeneity, and the Michaelis constants (Km values) and turnover numbers (kcat values) for various penicillin and cephalosporin substrates were determined. Whereas Km values of the four beta-lactamases were comparable for penicillin G, cephalothin, and cefamandole, the type A and D enzymes exhibited greater affinity than the type B and C beta-lactamases for nitrocefin, cefazolin, and cephapirin. Conversely, the type B and C beta-lactamases exhibited greater kcat values than the type A and D enzymes against most of the cephalosporin agents, excluding nitrocefin. In contrast to earlier reports suggesting that the type B beta-lactamase is relatively inefficient in hydrolyzing penicillin G, we found only minor differences in the specific activities and kcat values of the type A, B, and C beta-lactamases. The type D beta-lactamase was distinctly less active against penicillin G, however, exhibiting only 15 to 25% of the kcat values of the other beta-lactamases. More than a 2,000-fold difference between the relative efficiencies of hydrolysis (kcat/Km) of cefazolin and cefuroxime by the type A beta-lactamase exists. This greatly exceeds the 60-fold difference in the stability of penicillin G and cefazolin with the same enzyme. Whereas the isoelectric points of the type A, B, and C beta-lactamases were similar, the value for the type D beta-lactamase was distinguishably lower (10.1 for types A, B, and C and 9.7 for type D). We conclude that marked differences in the stability of commonly used beta-lactams to hydrolysis by the staphylococcal beta-lactamases are present. This heterogeneity and the clinical implication thereof need to be considered in the antibiotic management of staphylococcal infection.

Cephalosporins↗
PubMed1974

Comparative serum levels and protective activity of parenterally administered cephalosporins in experimental animals.

Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs.

Animals↗
PubMed1976

Relative morphological effects induced by cefoxitin and other beta-lactam antibiotics in vitro.

Cefoxitin, a new semisynthetic cephamycin antibiotic, induced filament formation at subinhibitory concentrations with a beta-lactamaseless strain of Enterobacter cloacae (HSC 18410 M66). The extent of filament induction by cefoxitin was similar to that seen with cephalothin, cefazolin, and benzylpenicillin. Filament induction by cefoxitin was markedly less than that seen with cephalexin, carbenicillin, ticarcillin, cephradine, and cephapirin. Antibiotics which failed to induce filaments at any level tested included cephaloridine, cephacetrile, cephalosporin C, the cephamycins, 6-aminopenicillanic acid, 7-aminocephalosporanic acid, A16884, A16886, and FL-1060. Those antimicrobial agents tested which lacked an aromatic substituent in the 7-position (for cephems) or in the 6-position (for penams) did not induce filaments. These observations suggest a possible relationship between filament induction of the test organism and the molecular nature of constituents in the 7- or 6-position of beta-lactams.

Anti-Bacterial Agents↗
PubMed1976

In vitro and clinical studies of cefatrizine, a new semisynthetic cephalosporin.

Cefatrizine, a new oral semisynthetic cephalosporin, was evaluated in vitro and in the treatment of 18 patients with acute urinary tract infection, pneumonia, and soft tissue infection. In vitro, it was more active than cephalexin for gram-positive and gram-negative bacteria. It was also more active than cephalothin, cefazolin, and cephapirin against most of the gram-negative bacteria but less active against the gram-positive bacteria. Of the patients treated with cefatrizine, only one failed to respond. This patient had pneumococcal conjunctivitis and hypogammaglobulinemia and neutropenia. The mean peak serum level after multiple 6-hourly doses of 500 mg was 6.2 mug/ml. The serum levels of cefatrizine necessary for inhibition of most susceptible organisms were well within the achievable range. The drug was well tolerated, and no renal, hepatic, or hematological toxicity was detected.

Administration, Oral↗
PubMed1976

Relative inactivation by Staphylococcus aureus of eight cephalosporin antibiotics.

These studies extend the recent observation that cefazolin is inactivated to a greater extent than cephaloridine by some strains of penicillinase-producing Staphylococcus aureus, whereas cephalothin undergoes little if any inactivation. In Mueller-Hinton broth (inoculum, 3 x 10(6)) 100 recently isolated strains had minimal inhibitory concentrations (MICs) </= 2 mug/ml for cephalothin and cephaloridine, whereas in Trypticase soy broth (TSB) 50% had MICs > 2 mug/ml and 10% (designated "resistant" strains) were >8 mug/ml for cephaloridine but remained </=2 mug/ml for cephalothin. A large inoculum (3 x 10(7)) of strains with high MICs in TSB almost completely inactivated 50 mug of cefazolin per ml in 6 h, with progressively less inactivation, in the following order, of cephaloridine, cephalexin, cephradine, cephapirin, and cefamandole; cefoxitin and cephalothin underwent little if any inactivation. The greater inactivation in TSB than in Mueller-Hinton broth appeared to be due to a greater production of beta-lactamases by each colony-forming unit, since the inoculum size in the two broths was not significantly different. In contrast, "susceptible" strains (MICs </= 2 mug/ml in both broths) inactivated cephaloridine more than cefazolin, and equal amounts of powdered bacterial extracts confirmed the fact that qualitatively different beta-lactamases were produced by the susceptible and resistant strains. Disk diffusion tests were unreliable in separating the two groups of staphylococci. The clinical significance of inactivation by strains with high MICs is not known but, unless susceptibility can be clearly established, cephalothin appears preferable for severe staphylococcal infections, since it undergoes little if any inactivation by any strains of staphylococci.

Cephalosporins↗
PubMed2003

In vitro activity of 10 antimicrobial agents against bacteria isolated from cows with clinical mastitis.

The susceptibility of 495 strains of bacteria, recently isolated in France from cows with clinical mastitis, to 10 antimicrobial agents--penicillin G, cloxacillin, oxacillin, cephalexin, cefazolin, cephapirin, cefquinome, neomycin, ampicillin and colistin--was determined by measuring their minimum inhibitory concentrations (MICS). Overall, the levels of resistance were very low except for staphylococci and penicillin G. The 167 streptococcal strains were susceptible to all of the beta-lactams tested, but six (3-6 per cent) were highly resistant to neomycin. Of the 171 staphylococcal isolates, 36.2 per cent were resistant to penicillin G, one strain of Staphylococcus sciuri was classified as methicillin-resistant, but they were all susceptible to neomycin. None of the 122 strains of Escherichia coli was resistant to colistin, but 12 had high MIC values for one or more of the cephalosporins.

Animals↗
PubMed1979

Antibiotic sensitivity and synergism of 'penicillin-tolerant' Staphylococcus aureus.

15 Staphylococcus aureus strains were isolated from 15 patients with staphylococcal bacteremia. Eight of these strains were shown to be tolerant for cloxacillin. Cloxacillin-tolerant strains were also tolerant for most of the cephalosporins tested except for cephapirin. Strains were not tolerant for clindamycin and gentamicin. Penicillin-tolerant staphylococci showed a high degree of synergism between gentamicin and cloxacillin or cephalothin and gentamicin.

Anti-Bacterial Agents↗
PubMed1984

Epileptogenic activity induced by intravenous injection of certain cephalosporins in rats.

Epileptogenic activity induced by intravenous injection of certain cephalosporin derivatives was studied. Ceftezole provided the most potent epileptogenic activity among the drugs tested. Changes in seizure patterns on electroencephalogram (EEG) tracings and behavioral signs after administration of cefotiam and cefazolin were similar to those seen after ceftezole, though the intensity and duration were less than those of ceftezole. Cephacetrile and cephaloridine elicited the spiking activity in the frontal cortex and the other regions without apparent behavioral changes. Latamoxef and cefmenoxime displayed a weak epileptogenic activity at a dose of 1000 mg/kg. On the other hand, cephapirin, cefmetazole and cefoxitin did not evoke any changes in EEG nor in behavior. Penicillin G at a dose of 200 mg/kg affected spike or spike-and-wave complex in a few cases, but at a dose of 500 mg/kg the animals died of dyspnea almost immediately after injection without showing apparent epileptogenic signs. These results suggest that some of cephalosporins such as ceftezole, cefotiam, cephacetrile and cefazolin provide epileptogenic activity at higher doses.

Animals↗
PubMed1991

Mastitis in beef cows and its effects on calf weight gain.

Quarter milk samples from 51 purebred (Angus, Polled Hereford, and Simmental) and 69 crossbred (Angus x Simmental x Charolais three-way cross) beef cows were collected aseptically at three times during lactation to determine the prevalence of intramammary infection, milk somatic cell counts (SCC), and effects of infection on calf weight gain. Quarter infection prevalence was 13.1, 14.9, and 27.5% in early, mid, and late lactation; corresponding cow infection prevalence was 25.8, 29.2, and 54.4%. Staphylococcus aureus was isolated from 2.9, 2.7, and 3.2% of quarters in early, mid, and late lactation, respectively. Corynebacterium bovis, generally regarded as a minor pathogen, was isolated from 4.0, 7.6, and 18.2% of quarters at the three respective times. Geometric SCC means (10(3) cells/ml) were 1,522, 344, and 509 for S. aureus-infected quarters; 344, 899, and 221 for Staphylococcus hyicus-infected quarters; 65, 36, and 86 for C. bovis-infected quarters; and 20, 17, and 18 for uninfected quarters in early, mid, and late lactation, respectively. Adjusted 205-d weight gain for calves with S. aureus-infected dams was 9.6 kg less (P less than .05) than for calves with uninfected dams. Adjusted 205-d weight gain for calves with dams infected with any mastitis pathogen did not differ significantly from that of calves with uninfected dams. At weaning half of the infected cows and half of the uninfected cows were given an intramammary infusion product containing 300 mg of cephapirin benzathine in each quarter; the remaining cows were untreated controls. Quarter samples were collected aseptically from all cows 14 to 28 d after subsequent calving. Quarter prevalence of infection after calving was lower (P less than .05) in treated (8.2%) than in control (22.4%) cows. Significantly more infections present at weaning were eliminated in treated than in control cows, but the new infection rate during the dry period and early lactation did not differ between the two groups.

Age Factors↗
PubMed1992

beta-Lactam antibiotic modulation of murine neutrophil cytokinesis.

Fourteen cephalosporins, 11 penicillins and 1 monobactam were evaluated for their in vitro modulation of murine neutrophil cytokinesis. As a result, the beta-lactam antibiotics were placed into 6 groups based on their effect on random (R) and FMLP-directed (D) migration [Group 1 (no effect): cephalosporin C; Group 2 (R-->D decreases): cloxacillin, cefotaxime, ceftazadime, cefuroxime, cephalothin, cephapirin, cephadine, nafcillin, piperacillin, ticarcillin, ampicillin, oxacillin, aztreonam; Group 3 (R increases D-->): cephaloridine; Group 4 (R increases D increases): cefsulodin; Group 5 (R increases D decreases): cefoperazone, cefoxitin, ceftriaxone, 6-amino-penicillanic acid; Group 6 (R decreases D decreases): cefadroxil, cefazolin, penicillin G, methicillin]. Trypan blue exclusion studies showed that inhibition of R and D by Group 6 beta-lactam antibiotics is not due to overt cytotoxicity. beta-lactam antibiotics inhibiting D also increased neutrophil adherence to plastic at a concentration of 1000 microM. Finally, the [Ca++] inhibitor chlorpromazine significantly abrogates beta-lactam- and FMLP-directed migration at a test concentration of 1 microM.

Animals↗
PubMed2006

Effects of prepartum intramammary antibiotic therapy on udder health, milk production, and reproductive performance in dairy heifers.

Preparturient heifers (n = 561) from 9 herds in 6 US states and 1 Canadian province were enrolled in a study to test the hypothesis that prepartum intramammary therapy would cure existing intramammary infections (IMI) and lead to increased milk production, reduced linear somatic cell count (LSCC), and improved reproductive performance. Mammary secretions were collected 10 to 21 d before expected calving from each quarter. Heifers were then assigned by identification number to receive intramammary therapy consisting of infusion of one tube per mammary quarter of a lactating cow commercial antibiotic preparation containing cephapirin or to a nontreated control group. Overall, 34.1% of mammary quarters were infected with a mastitis pathogen before parturition and 63.4% of heifers had at least one mammary quarter infected. The coagulase-negative staphylococci (CNS) caused the majority (74.8%) of prepartum IMI. Coagulase-positive staphylococci, environmental streptococci, and coliforms accounted for 24.5% of prepartum infections. Treatment had a significant effect on the cure rate of infected mammary quarters. Mammary quarters that were infected prepartum and treated with antibiotics had a 59.5% efficacy of cure rate and the percentage reduction in heifers with IMI was 51.9. Control quarters had a spontaneous cure rate of 31.7%. Treatment did not significantly affect milk production or LSCC in the first 200 d of lactation; however, there was a significant treatment by herd interaction for milk production. Quarters cured of either CNS or major pathogens had a lower LSCC in the first 200 d of lactation. No significant effect on services per conception or days open between treatment and control groups was observed. This trial demonstrated that prepartum intramammary antibiotic therapy did reduce the number of heifer IMI postpartum. Milk production, LSCC, and reproductive performance during the first 200 d of the first lactation were not significantly affected by treatment. Given these results, use of prepartum intramammary antibiotic therapy in heifers as a universal strategy to increase milk production in first-lactation dairy cows may not be warranted.

Animals↗
PubMed2007

Treatment practices and quantification of antimicrobial drug usage in conventional and organic dairy farms in Wisconsin.

The objective of this study was to develop a method to quantify antimicrobial drug usage and treatment practices on conventional and organic dairy farms that had been recruited to represent a broad spectrum of potential exposure to antimicrobial drugs. Data on disease prevalence and treatment practices of organic (n = 20) and conventional (n = 20) farms were obtained during a farm visit using a survey instrument. A standardized estimate of antimicrobial drug usage was developed using a defined daily dose (DDD) of selected compounds. Density of antimicrobial drug usage was expressed as the number of DDD per adult cow per year. Differences in prevalence and management of selected diseases between conventional and organic farms were identified. The overall estimated prevalence of selected diseases was greater for conventional farms compared with organic farms. Organic farmers reported use of a variety of nonantimicrobial compounds for treatment and prevention of disease. Conventional farmers reported that penicillin was the compound most commonly used for dry cow therapy and cephapirin was most commonly used for treatment of clinical mastitis. On conventional farms, the estimated overall exposure to antimicrobial drugs was 5.43 DDD per cow per year composed of 3.58 and 1.85 DDD of intramammary and parenteral antimicrobial drugs, respectively. Of total intramammary antimicrobial drug usage, treatment of clinical mastitis contributed 2.02 DDD compared with 1.56 DDD attributed to the use of dry cow therapy. Of total parenteral treatments, the distribution of exposure was 0.52 (dry cow therapy), 1.43 (clinical mastitis treatment), 0.39 (treatment of foot disease), 0.14 (treatment of respiratory disease), and 0.32 (treatment of metritis) DDD. For treatments of foot infections (0.33 DDD), respiratory infections (0.07 DDD), and metritis (0.19 DDD), the mean density of ceftiofur usage was significantly greater compared with other compounds.

Animals↗
PubMed1983

Cost benefit analysis of lactation therapy with somatic cell counts as indications for treatment.

Lactating dairy cows (487) from five commercial herds were in a study of benefits from lactation therapy of sub-clinical mastitis. Bacterial isolations and composite milk samples for somatic cell counts were taken from each cow each month for 15 mo. Cows (254) in the experimental group were infused with cephapirin in all quarters for two consecutive milkings if somatic cell counts rose above 400,000 cells/ml; 103 cows were so treated. Stepwise regression showed that lactation number, somatic cell counts, days in milk, and percent quarters infected explained variation in milk production, but treatment group, herd, and season did not. Also, there were no significant differences between production of infected experimental and control cows with high somatic cell counts on test dates after treatment. With the experimental program, there was a net loss of +19.65/cow. Intramammary lactation therapy based on somatic cell counts less than 400,000 cells/ml is not recommended.

Animals↗
PubMed1984

Residues in colostrum following antibiotic dry cow therapy.

Cows from five dairy herds were used to determine persistence of antibiotic residues in colostrum and milk following dry cow therapy. Cows were treated in all quarters at drying off with antibiotics approved for use for nonlactating cows. Antibiotics procaine penicillin G plus dihydrostreptomycin, novobiocin, cloxacillin, or cephapirin were compared with no treatment. Composite colostrum samples were collected from each cow at first milking after parturition. Samples were screened for residues by Delvotest P. Colostrum samples positive by Delvotest also were tested by Bacillus stearothermophilus disc assay. Four of 186 colostrum samples from cows treated with antibiotics at drying off were positive for residues by Delvotest. Only one was confirmed positive by disc assay following heat treatment. All colostrum samples from 48 cows not treated were negative. Samples of first marketable milk also were collected. Over 96% of milk samples from cows treated at drying off and 100% of milk samples from cows not treated were negative for residues by Delvotest. If manufacturer's recommendations are followed, antibiotic residues in colostrum and milk following dry cow therapy with products in our study should not be a significant problem.

Animals↗
PubMed1988

Persistence of residues in milk following antibiotic treatment of dairy cattle.

A study was conducted to determine the persistence of antibiotic residues in milk beyond the recommended withdrawal period. Composite milk samples (n = 122) were collected from 58 lactating dairy cows in the university herd receiving antibiotic treatments for any reason but only when administered as a single drug. Samples were obtained 72 h posttreatment and sampling continued every 24 h until result for antibiotic residue was negative by the Bacillus stearothermophilus disc assay. The antibiotic (n = 7) administered accounted for significant variation in drug persistence; however, route of administration, case number (for cows treated for more than one episode), number of days treated, animal's body weight, lactation number, and daily milk production did not affect drug persistence. Chi-square analysis indicated that 21% of milk samples were positive for residues beyond the recommended withholding period. Milk samples from cows treated with cephapirin and penicillin were the only samples that exceeded recommended withdrawal times. Often doses administered exceeded label directions.

Animals↗
PubMed1995

Modified microbiological method for the screening of antibiotics in milk.

The Bacillus stearothermophilus disc assay is routinely used by the dairy industry to screen milk for antibiotic residues. Although the assay detects the presence of beta-lactam antibiotics, it does not distinguish cephalosporins from other beta-lactam antibiotics. In this study, the B. stearothermophilus disc assay was modified to allow it to distinguish parent ceftiofur from other antibiotics by incorporation of the enzymes penicillinase and cephalosporinase into the assay. The modified B. stearothermophilus disc assay involves determining the zone of inhibition of a sample on an agar plate after the plate was incubated at 65 degrees C for 2.5 to 3 h as well as determining the zone of inhibition after the sample was treated with penicillinase or cephalosporinase. Samples in which this zone diameter was > 19 mm and < or = 25 mm were interpreted using the data from the primary assay. Samples with zone diameters > 25 mm must be diluted 2- to 10-fold and reassayed to obtain a zone diameter > 19 and < or = 25 mm, for proper interpretation. Samples with zone diameters > or = 16 mm and < or = 19 mm must also be reassayed using dilute enzyme solutions for proper interpretation. When these modifications of the B. stearothermophilus disc assay are used, ceftiofur can be distinguished from ampicillin, amoxicillin, penicillin, cephapirin, cloxacillin, novobiocin, and pirlimycin for samples with zone diameters > or = 16 mm. This assay cannot, however, separate ceftiofur from cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗