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PubMed1978

Cephalosporin antibiotics in therapy of experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis in rabbits.

Six cephalosporin antibiotics (cefamandole, cefazolin, cephacetrile, cephalothin, cephaloridine, and cephradine) and two penicillin (ampicillin and penicillin G) were evaluated in vitro and in a rabbit model of experimental meningitis due to Haemophilus influenzae or Streptococcus pneumoniae. The percentage penetration ([concentration in cerebrospinal fluid/concentration in serum] X 100%) of these antibiotics varied from 0.7% for cephalothin to 17% for cephaloridine. The penetration varied inversely with binding to serum proteins. The bactericidal rate of all of the cephalosporin antibiotics was similar in vitro and in vivo to that of penicillin G. However, as demonstrated with cephalothin, concentrations considerably above the minimal bactericidal concentration (as determined in broth) were necessary to initiate the bactericidal effect. Cefamandole was found to be as effective as ampicillin in the therapy of H. influenzae meningitis in rabbits.

Ampicillin↗
PubMed1978

The nephrotoxicity of cephalosporins: an overview.

The cephalosporin antibiotics cephaloridine and cephalothin are known to cause renal damage. Experience with newer congeners is not yet sufficient to predict their potential nephrotoxocity. The renal lesion produced by cephaloridine is primarily due to the intrinsic toxicity of this drug for the cells of the proximal renal tubule and depends upon its peculiar transport characteristics. In contrast, renal injury due to cephalothin resembles that seen with the penicillins. Thus, some instances of cephalothin nephropathy appear to be toxic in nature with a histologic picture of acute tubular necrosis, whereas others exhibit signs of hypersensitivity including rash, eosinophilia, and interstitial nephritis. Among the factors alleged to contribute to the nephrotoxicity of cephalosporins is their administration with aminoglycosides. Although the physician should be aware of the possibility of a potential adverse interaction between these groups of antibiotics, the evidence is not sufficiently conclusive to warrant avoidance of the combination when it appears to be therapeutically useful.

Aminoglycosides↗
PubMed1978

Pharmacokinetics of cephalosporins in patients with normal or reduced renal function.

The pharmacokinetic distribution of 10 cephalosporin compounds, cephalothin, cephaloridine, cephaloglycine, cephalexin, cefazolin, cephapirin, cephradine, cephacentrile, cefoxitin, and cefamandole, in patients with various degrees of renal function was reviewed. The mean serum half-life (t1/2) of each cephalosporin compound was calculated from reported data in patients grouped according to their degree of renal function, as determined by the rate of creatinine clearance. Mean t1/2 values in patients with normal renal function were compared with t1/2 values for the same cephalosporin in patients with moderate renal failure and severe renal azotemia. The effect of hemodialysis and peritoneal dialysis on the mean serum t1/2 of each cephalosporin was also determined. The mean serum t1/2 of each cephalosporin progressively increased as the rate of creatinine clearance decreased. Hemodialysis decreases the t1/2 of cephaloridine, cephalexin, cefazolin, and cephacetrile but only minimally influences the t1/2 of cephalothin and cefamandole. Peritoneal dialysis reduces the t1/2 of cephalothin and cephaloridine but only minimally influences the t1/2 of cefazolin and cefamandole.

Cephalexin↗
PubMed1978

Therapy with hyperbaric oxygen for experimental osteomyelitis due to Staphylococcus aureus in rabbits.

Hyperbaric oxygen (HBO) is used as adjunctive therapy of chronic osteomyelitis, but its efficacy remains controversial. A recently developed rabbit model for osteomyelitis due to Staphylococcus aureus was used to compare the results of treatment with HBO, cephalothin, a combination of both, or no treatment. Cultures of bone were positive in 10 (91%) of 11 control animals (untreated), five (36%) of 14 animals treated with HBO, eight (47%) of 17 treated with cephalothin, and six (40%) of 15 treated with HBO plus cephalothin. All three treatment groups differed significantly from untreated controls in the number of positive cultures obtained (P less than 0.01), but there were no significant differences among treatment groups. In vitro growth and killing curves (1.0 microgram of cephalothin/ml) constructed after exposure to HBO revealed no change from parallel control studies in ambient air. These data demonstrate that therapy with HBO is at least as effective as antibiotic therapy. The therapeutic effectiveness of HBO does not appear to be related to antibacterial activity.

Animals↗
PubMed1994

Double-blind randomized prospective study of the efficacy of antibiotic prophylaxis for open reduction and internal fixation of closed ankle fractures.

Antibioprophylaxis has been proven to be efficient for some orthopaedic procedures. However, its efficacy for clean limited procedures with metallic implants is not clear. One hundred twenty-two closed ankle fracture patients undergoing open reduction and internal fixation were randomized, double-blindly, to receive either cephalothin (1 g i.v. every 6 h x four doses) or a placebo starting before tourniquet application. Mean trauma-surgery delay was 30.2 h, and average tourniquet duration was 65.4 min. Four patients (three of 62 on placebo and one of 60 on cephalothin) developed a superficial wound infection. One of the patients in the placebo group was hospitalized and treated with i.v. antibiotics. However, there was no osteomyelitis or premature hardware removal. The difference between the two groups was not statistically significant (chi 2 test of appreciation p = 0.33, two-tailed probabilities). Therefore, cephalothin prophylaxis does not seem justified in this patient population. A larger series is needed to avoid a type II error.

Adult↗
PubMed1998

Antimicrobial susceptibility of oral isolates of Enterobacter cloacae and Klebsiella pneumoniae from a southern Chinese population.

The antibiotic susceptibilities of 59 Enterobacter cloacae and 39 Klebsiella pneumoniae human oral isolates collected from a southern Chinese population in Hong Kong were investigated for their susceptibility to eight antibiotics: ampicillin, cephalothin, cefuroxime, ceftazidime, ciprofloxacin, gentamicin, tetracycline and trimethoprim/sulfamethoxazole using the E-Test method for direct quantification of minimum inhibitory concentrations. Most strains were sensitive to all antibiotics except ampicillin and cephalothin. Ampicillin resistance was exhibited by 82% of K. pneumoniae and 69% of E. cloacae isolates. Eighty-eight percent of E. cloacae isolates were resistant to cephalothin. Several strains fell within the intermediate category of sensitivity for ampicillin (E. cloacae and K. pneumoniae), cefuroxime (E. cloacae) and tetracycline (K. pneumoniae). Comparison with other Hong Kong data suggests that resistance rates to cefuroxime, ceftazidime, ciprofloxacin, gentamicin, tetracycline and trimethoprim/sulfamethoxazole exhibited by the oral isolates are generally lower than in enterobacters and Klebsiella spp. isolated from urine, skin and soft tissues in Hong Kong populations.

Adult↗
PubMed1978

Drug-induced lysosomal changes and nephrotoxicity in rats.

Lysosomal involvement in renal tubular lesions was studied mainly by electronmicroscopy after single and repeated administrations of cephacetrile, cephalothin, cephaloridine, gentamicin or leupeptin and combine administrations of cephalothin and gentamicin or gentamicin and leupeptin in female Wistar rats. Large cytosomes of high density were increased due probably to either reabsorption and secretion of drugs or their metabolites. These cytosomes displaying acid phosphatase activity were demonstrated histochemically and were identified as heterolysosomes. In rats treated with cephaloridine, gentamicin or leupeptin, disruption of lysosomal membrane was noted and regional cytoplasmic destruction was seen in the vicinity of the disrupted heterolysosomes. Necrotic epithelial cells and renal insufficiency were observed in these animals. On the other hand, neither destruction of lysosomes nor cell lesion was found in rats treated with cephacetrile or cephalothin. It was speculated that lysosomal destruction might be the cause of the cell lesions found in cephaloridine, gentamicin or leupeptin treated rats.

Animals↗
PubMed1977

Exudate levels and bactericidal activity of cefazolin in a new local infection system using rat granuloma pouches.

An experimental local infection system has been developed in which exudates are induced with croton oil in granuloma pouches of rats. This system provided a suitable model for the evaluation of the therapeutic effect of two antibiotics, cefazolin and cephalothin. Exudate levels of cefazolin were found to be higher than those of cephalothin, and these levels correlated with the higher serum level of cefazolin. The therapeutic effect of cefazolin, after intramuscular injection of 20 mg of each antibiotic per kg, was superior to that of cephalothin in eradicating both Staphylococcus aureus and Escherichia coli.

Animals↗
PubMed1977

Results of a clinical trial of cefoxitin, a new cephamycin antibiotic.

Cefoxitin was administered intravenously to 143 patients, 67% of whom were seriously ill. The rate of cure or improvement was 93%. The study was conducted in two phases; the first was an open, controlled clinical comparison of cefoxitin and cephalothin. In this phase, 28 patients received cefoxitin and 29 received cephalothin. In the second phase, cefoxitin alone was used for the treatment of an additional 115 patients. Twenty bacteremic patients treated with cefoxitin were cured or improved in 95% of cases. The infecting organism was eradicated in all bacteremic patients. All of 14 anaerobic or predominantly anaerobic infections were cured or improved. The infecting anaerobic organism was eliminated in 86% of the cases. Twenty-five patients infected by cephalothin-resistant, cefoxitin-susceptible gram-negative rods were cured. Three patients each with infective endocarditis and osteomyelitis were cured. The incidence of adverse experiences was: 1.4% drug eruption; 2% each asymptomatic serum transaminase elevation and leukopenia; and 2.5% asymptomatic eosinophilia. The incidence of severe thrombophlebitis was 5%. No permanent or serious adverse reactions were encountered. Although the numbers of patients in some categories were too small to permit statistical evaluation, I feel that cefoxitin may be a useful new antibiotic for treatment of infections caused by cehalothin-resistant bacteria and by anaerobic organisms.

Adult↗
PubMed1979

Susceptibility and synergy studies of methicillin-resistant Staphylococcus epidermidis.

Methicillin-resistant Staphylococcus epidermidis is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution minimum inhibitory concentrations were determined for 100 strains of methicillin-resistant S. epidermidis which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at </=3.12 mug/ml, whereas clindamycin inhibited only 46 strains at </=12.5 mug/ml. Methicillin-resistant S. epidermidis strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of >/=3.12 mug/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at </=25 mug/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (>/=10(2) kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 mug/ml) plus cefamandole (6.25 mug/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 mug/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 mug/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 mug of rifampin per ml developed in three of five methicillin-resistant S. epidermidis strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant S. epidermidis infections are indicated.

Anti-Bacterial Agents↗
PubMed1981

Cefoperazone treatment of experimental endocarditis.

Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.

Animals↗
PubMed1987

Effects of cefonicid and other cephalosporin antibiotics on male sexual development in rats.

The purpose of this study was to determine whether cefonicid, a cephalosporin antibiotic with a modified N-methylthiotetrazole (MTT) side chain, caused testicular toxicity when subcutaneously administered to Sprague-Dawley male rats from days 6 to 36 postpartum at doses of 50 to 1,000 mg/kg per day. Moxalactam (a cephamycin antibiotic which will be referred to as a cephalosporin for convenience throughout), which contains the MTT side chain, was used as a positive control and was administered at 100 to 1,000 mg/kg per day, and cephalothin, which lacks an MTT side chain, was used as the negative control at 1,000 mg/kg per day. Moxalactam caused a significant reduction in testicular and seminal vesicle weights in 37-day-old animals, and histological examination revealed bilateral multifocal atrophy of the seminiferous tubules at all dose levels. Animals reared to reproductive maturity had significant deficits in fertility, and histological examination revealed multifocal or diffuse atrophy of the seminiferous tubules at all doses with a severity greater than that observed in the 37-day-old animals. The histological findings were confirmed by marked reductions in testicular sperm production rates and cauda epididymal sperm numbers. Cephalothin and cefonicid had no treatment-related adverse effects on the sexual maturation of prepubertal, juvenile, or adult males. The absence (in cephalothin) or modification (in cefonicid) of the MTT side chain was not associated with adverse reproductive effects. The relevance of these findings to humans in prenatal and prepubertal stages of life cannot be determined at this time.

Age Factors↗
PubMed1968

Differentiation of Klebsiella-Enterobacter (Aerobacter)-Serratia by biochemical tests and antibiotic susceptibility.

Studies were undertaken for the differentiation of members of the Klebsiella-Enterobacter (Aerobacter)-Serratia division by biochemical tests and antibiotic susceptibility. A total of 67 cultures were tested. Strain identification was readily accomplished with the use of motility tests and arabinose fermentation. In addition, a practical schema, based on sensitivity pattern, proved valuable in the classification of the different strains. Most (if not all) Klebsiella strains were susceptible to cephalothin, and all were sensitive to colistin. Enterobacter strains were resistant to cephalothin but susceptible to colistin. In contrast to those other members of the group, all Serratia strains were resistant to both cephalothin and colistin. The combination of a limited number of biochemical reactions and single-disc sensitivity tests appears to be a logical approach for the tentative identification of Klebsiella-Enterobacter (Aerobacter)-Serratia strains.

Bacteriological Techniques↗
PubMed1980

Discrepancies between results obtained by agar and broth techniques in testing of drug combinations.

One hundred strains of Staphylococcus epidermidis were tested by the double-disk agar diffusion method for their susceptibility to cephalothin, to sulfamethoxazole-trimethoprim, and to combinations of these drugs. Forty-five strains showed a bridging inhibition zone between the two disks, suggesting a synergistic effect of the combination of cephalothin plus sulfamethoxozole-trimethoprim against these strains. Ten of these strains were retested against the individual drugs and their combination by the twofold broth dilution method. No strain showed higher susceptibility to any combination as compared with cephalothin alone.

Cephalothin↗
PubMed1982

Reliability of the MS-2 system in detecting methicillin-resistant Staphylococcus aureus.

The MS-2 system (Abbott Diagnostics, Division of Abbott Laboratories, Dallas, Tex.) is an automated system capable of rapid antimicrobial susceptibility testing. However, the short incubation periods used by the device may adversely affect its ability to detect slowly growing resistant organisms. Shortly after the introduction of the MS-2 system into the University of Mississippi Medical Center clinical microbiology laboratory, we noted discrepancies between the MS-2 and the disk diffusion susceptibility reports when methicillin-resistant Staphylococcus aureus isolates were tested. Subsequently, we determined the susceptibilities of 75 such isolates by the MS-2 and Kirby-Bauer disk diffusion methods and measured the minimum inhibitory concentrations of methicillin, oxacillin, and cephalothin for 33 of the 75 isolates by standardized agar dilution techniques. There was only 47% overall agreement between the MS-2 and disk diffusion methods when methicillin was tested and 15% agreement when cephalothin was the test drug. There was 93% or more overall agreement between the two methods when other antimicrobial agents were tested. The minimum inhibitory concentration of methicillin was greater than or equal to 16 micrograms/ml for all 33 isolates evaluated by the agar dilution method. A comparison of the MS-2 and agar dilution results revealed an overall agreement of 49% when the susceptibilities to methicillin were determined. The MS-2 system reported that multiple methicillin-resistant S. aureus isolates obtained from a single patient were either resistant, intermediate, or sensitive to methicillin. Inconsistent results were also obtained when a single isolate was tested simultaneously in 10 cuvette cartridges. We conclude that the MS-2 system does not reliably detect methicillin and cephalothin resistance among S. aureus.

Cephalothin↗
PubMed1983

Evaluation of the cefonicid disk test criteria, including disk quality control guidelines.

Cefonicid (SKF 75073) is a second-generation cephalosporin which has a spectrum of antimicrobial activity similar to that of cefamandole, but cefoxitin (a cephamycin) and cephalothin have uniquely different spectra of activity. The second-generation cephalosporins tested displayed comparable susceptibility to beta-lactamases and inhibited type I beta-lactamases. Although cefonicid has a longer serum half-life (3 to 4 h) compared with the currently used drugs, the same minimal inhibitory concentration breakpoints separating susceptible and resistant categories were applied to tests with cefonicid, cefamandole, and cephalothin. Regression analysis of the disk diffusion test results confirmed the use of identical zone size breakpoints for 30-micrograms cefonicid, cefamandole, and cephalothin disks: all three produced similar parabolic regression lines. Further analysis of disk test data confirmed the fact that cefonicid and cefamandole disks might be used interchangeably. But for routine tests, cefonicid disks might be preferred in order to minimize the number of very major (false-susceptible) interpretive errors. Suggested cefonicid 30-micrograms disk interpretive criteria are: susceptible, greater than or equal to 18 mm (less than or equal to 8.0 micrograms/ml), and resistant, less than or equal to 14 mm (greater than 16 micrograms/ml). Quality control zone diameter limits were calculated from data obtained in a multilaboratory collaborative study.

Bacteria↗
PubMed1983

Organic anion infusions exacerbate experimental acute renal failure.

UNLABELLED: This investigation proposed to determine whether high organic anion (OA) loads per nephron increase renal susceptibility to acute ischemic and nephrotoxic injury. Anesthetized Sprague-Dawley rats were infused with a control infusate, Na2SO4, or an OA (hippurate, p-aminohippurate, cephalothin; 0.125-1.0 mg/min). After a 40-min control period, acute renal injury was induced by either bilateral renal pedicle cross-clamping (X25 min) or by HgCl2 administration (12 mg/kg i.v.). Glomerular filtration rate (clearance of [125I]iothalamate) was determined every 20 min before and after renal injury. Non-OA-infused rats lost 51 +/- 4% (ischemia) and 40 +/- 4% (HgCl2) of control GFR. OA infusion exacerbated this loss of renal function (ischemia, 89 +/- 2%; HgCl2, 84 +/- 4%). Renal histology demonstrated that OA-treated acute renal failure (ARF) rats had more vacuolar degeneration of proximal tubular cells (HgCl2, ischemia) and greater tubular dilatation (ischemia) than did non-OA-treated ARF rats. These functional and histologic responses to OA infusion were not OA dose dependent. Discontinuation of OA infusion did not cause a subsequent rise in GFR. Na2SO4 infusion had no detrimental effects on ischemic ARF. Control rats subjected to prolonged OA infusion (1 mg/min X 5 h) maintained stable GFR and had normal renal histology. ARF rats infused with low-dose cephalothin had terminal serum cephalothin concentrations within a range commonly seen in humans. CONCLUSION: organic anion infusions can exacerbate early functional and histologic parameters of experimental ARF.

Acute Kidney Injury↗
PubMed1998

Evaluation of allergenic potential of low-molecular compounds by mouse popliteal lymph node assay.

In the present study, the correlation between mouse PLNA results and those obtained from GP-PCA and from GP-ASA reactions for sodium 2,4,6-trinitrobenzenesulfonate dihydrate (TNBS), penicillin G and cephalothin was investigated. Next, various drugs were tested using the mouse PLNA to study whether PLN reactivity could be related to the potential of the compounds to induce allergic and autoimmune disorders in humans. The parameter of the PLNA was determined by the PLN cellularity index in BALB/c and A/J mice treated with a single subcutaneous injection of compounds. Hartley guinea pigs were immunized subcutaneously with the compounds without adjuvant, and then the GP-PCA and GP-ASA reactions were assessed. The examinations using mice and guinea pigs showed that mouse PLN responses to TNBS, penicillin G and cephalothin correlated with the allergenicity responses obtained in the GP-PCA reaction to three compounds. In the mouse PLNA, ten drugs considered to be well-known inducers of allergic side-effects in humans (i.e., penicillin G, cephalothin, ampicillin, carbenicillin, cefazolin, cefotaxime, streptomycin, 4-aminoantipyrine, chlorhexidine and sulfamethoxazole) caused increases in PLN cellularity indices as well. These results indicate that the PLNA may be useful as a short-term and simple test system for detecting low-molecular drugs exhibiting allergenicity potential.

Allergens↗