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Resistance of Staphylococcus aureus to semisynthetic penicillins and cephalothin.

Six strains of Staphylococcus aureus resistant to semisynthetic penicillins were recovered from clinical sources during a two-month period. Resistance was detected by standard disk sensitivity tests at 37 C. Two resistant strains were responsible for infections (one of which was fatal), and five strains were susceptible only to phage type 92. All of the strains produced penicillinase, which did not destroy oxacillin, and each was resistant to oxacillin at low inocula. Relative resistance to cephalosporin was demonstrable by the tube dilution assay but not by standard disk tests. The strains susceptible to phage type 92 were susceptible to vancomycin and to the synergistic action of oxacillin or cephalothin plus gentamicin.

Bacteriophage Typing↗

Safety and tolerance comparison of imipenem-cilastatin to cephalothin and cefazolin.

Imipenem-cilastatin was compared, in two multicentre clinical trials, with cefazolin or cephalothin, in their efficacy, safety, and tolerance. Safety and tolerance for imipenem-cilastatin was similar to that of these two cephalosporins. There were more transient liver function test changes in the imipenem-cilastatin group, but the frequency was similar to that for beta-lactams in general. There were similar numbers of cases of transient neutropenia in each group. Clinical side effects were few for the treatment groups and all drugs were well tolerated.

Cefazolin↗

Prospective comparative evaluation of gentamicin or gentamicin plus cephalothin in the production of nephrotoxicity in man.

Recent studies in animal models have demonstrated that in contrast with humans, cephalothin (CTIN) does not increase gentamicin (GENT) nephrotoxicity, but rather protects against it, particularly when CTIN is given simultaneously with GENT. To investigate this phenomenon in humans a study was designed in which 67 patients suffering from mild infections were investigated. Thirty-three of them served as the control group receiving GENT alone at a dose of 1.5 mg/kg/8 hourly, while the remaining 34 received CTIN at a dose of 2 g or 3 g 8 hourly by i.v. bolus, either simultaneously with GENT or separated by a 4-h interval. Findings showed that: (a) cylindruria developed in 66.6% and 82.3% and 82.3% in the GENT and GENT + CTIN groups respectively, (b) urinary beta-glycuronidase activity increased in 57.5% and 75% (c) serum creatinine exceeded by 0.3 mg the initial values in 21.2% and 27.6% and (d) the blood urea was above 50 mg% in 18.1% and 17.6% of the patients. These results indicate that: (a) regardless of the route and order of administration simultaneous treatment did not protect against nephrotoxicity in humans; (b) the combination of GENTA plus CTIN has no synergistic effect on the production of elevated serum creatinine and rising blood urea; (c) urinary beta-glycuronidase is not a significant predictor of eventual nephrotoxicity; (d) the following risk factors influenced the appearance of nephrotoxicity in both groups: (1) elevated GENT trough levels greater than or equal to 2 mg/l; (2) a course of treatment longer than 10 days.

Adult↗

Ceftazidime with or without vancomycin vs. cephalothin, carbenicillin and gentamicin as the initial therapy of the febrile neutropenic pediatric cancer patient.

In a 28-month randomized trial we compared ceftazidime (CAZ), an extended spectrum cephalosporin, with cephalothin, carbenicillin and gentamicin (KCG) as empiric therapy for febrile neutropenic pediatric cancer patients. Because of the occurrence of ceftazidime-resistant Gram-positive primary infections, vancomycin was added to CAZ after the first year of study. Of 206 evaluable episodes 76 (37%) were documented infections including 20 bacteremias; 130 (63%) episodes were caused by fever of unknown origin. The number of complete responses to initial therapy in patients with documented infections did not differ among regimens: 26 of 43 (61%) for KCG, 9 of 16 (56%) for ceftazidime and 8 of 16 (50%) for CAZ + vancomycin (not significant). In patients with fever of unknown origin, response without modification of the initial regimen was 52 of 62 (84%) in the KCG arm, 32 of 40 (80%) on CAZ and 23 of 29 (80%) in patients treated with CAZ + vancomycin (not significant). Modifications of the regimen were similar among all three groups and were due primarily to the use of empiric antifungal or antiviral therapy and to empiric treatment of interstitial pneumonia. Hypokalemia occurred in 25 of 105 patients treated with KCG and in 4 of 101 treated with CAZ or CAZ + vancomycin (P less than 0.001). No differences between the efficacy of KCG, CAZ and CAZ + vancomycin as initial empiric therapy were demonstrated.

Agranulocytosis↗

Acute interstitial nephritis during treatment with penicillin and cephalothin.

A case of non-oliguric acute interstitial nephritis during treatment with ampicillin, benzylpenicillin and cephalothin is reported. There were symptoms of drug hypersensitivity, including fever, exanthema, eosinophilia and elevated serum IgE. Renal biopsy showed marked interstitial edema and infiltration with numerous eosinophils, some mononuclear cells and giant cells, and scattered tubular damage, but normal glomeruli and vessels. There was no pathological deposition of immunoglobulins or complement in the renal tissue. Renal function recovered after withdrawal of antibiotics and treatment with steroids. The findings suggest a drug-induced, hypersensitivity-mediated pathogenesis of the renal lesions, with participation of both humoral and cell-mediated immunological reactions.

Acute Disease↗

Generalized rash induced by sulfhydryl drug in guinea pigs--a comparative study on it with cephalothin-induced rash in guinea pigs.

Adverse reactions produced by sulfhydryl compounds with active thiol groups have generally formed a distinctive pattern in man when they are viewed as a class. It has been reported that cutaneous SH-induced drug eruptions have a wide variety of clinical presentations; histologically, they show a pattern of eosinophilic necrosis and/or satellite necrosis similar to that seen in cutaneous graft vs host reactions. In the present experiments, guinea pigs were sensitized with cephalothin (CET) and thiol compounds such as tiopronin (TP), D-penicillamine, gold sodium thiomalate or thiomalate, using a method similar to that described previously. In lymphocyte stimulation tests, lymph node cells from the sensitized animals responded positively to spleen cells pulsed with each thiol compound. Intracutaneous tests revealed some positive reactions to each thiol compound; there was a tendency to produce a tuberculin type reaction with indurated erythema rather than the Jones-Mote type seen in CET-induced reactions. The dose-requirements for positive intracutaneous tests and generalized rash (GR) due to thiol compounds were lower than for CET, which required relatively large doses. Histologically, infiltration of basophilic cells was prominent in the skin lesions induced by intracutaneous tests with CET and in those of CET-induced GR. On the other hand, intracutaneous tests with TP following the induction of TP-induced GR revealed eosinophilic degeneration of epidermal cells, which was similar to the eosinophilic necrosis seen in cutaneous GVHR. Intracutaneous tests after the induction of CET-GR did not show any eosinophilic changes in the epidermal cells. These findings are reminiscent of the characteristics of eruptions induced by thiol compounds in man, which differ from the eruptions induced by CET.

Animals↗

Bacteria commonly isolated from keratitis specimens retain antibiotic susceptibility to fluoroquinolones and gentamicin plus cephalothin.

PURPOSE: Patients presenting with presumed infective keratitis were studied to determine predisposing factors, the current susceptibilities of the bacterial isolates to a range of relevant antibiotics, the success rate of topical antibiotic treatment of keratitis and predictors of failure of topical therapy. METHODS: Corneal scrapings taken from patients who presented between January 2002 and December 2003 to the Sydney Eye Hospital Emergency Department with keratitis were cultured. The minimum inhibitory concentration of selected antibiotics was determined for each bacterial isolate using an agar dilution technique. RESULTS: One hundred and twelve consecutive patients presented with corneal ulcers. Forty-seven of the 112 (42%) patients had a growth from the corneal scraping. Potential predisposing factors were identified in 64% of patients, most frequently contact lens wear (36% of patients). Coagulase-negative staphylococci were the most common species isolated. Other common organisms isolated include Pseudomonas aeruginosa, Corynebacterium spp., Staphylococcus aureus and Streptococcus spp. CONCLUSIONS: Most microorganisms isolated from patients with bacterial keratitis showed susceptibility to ciprofloxacin and aminoglycosides. Cephalothin plus aminoglycoside constituted an effective initial broad-spectrum antibiotic combination. The success rate of topical antibiotic treatment of corneal abscess is 89%. Predictors of failure include older age group, medium or large ulcer, culture-negative keratitis, hypopyon and poor visual acuity.

Adolescent↗

Gentamicin- and cephalothin-associated rises in blood urea nitrogen.

Standardized rates of drug-attributed rises in blood urea nitrogen were 8.6%, 2.9%, and 9.3%, respectively, in patients receiving gentamicin alone, cephalothin alone, and both drugs together. These results provide evidence against a substantial synergism between the two drugs in the production of impaired renal function.

Adult↗

Short-term storage of six penicillins and cephalothin in microdilution trays for antimicrobial susceptibility tests.

To perform microdilution antimicrobial susceptibility tests efficiently, broth dilutions of the antimicrobial drugs should be prepared in large batches and stored frozen until needed. Studies were carried out to document the stability of ampicillin, benzylpenicillin, carbenicillin, methicillin, oxacillin, nafcillin, and cephalothin in microdilution trays during storage at -20 and -60 C. No significant deterioration was noted after 21 days of storage, as detected by bioassay and by replicate minimal inhibitory concentration determinations with control organisms. No significant differences were noted moreover between trays stored for three weeks at -20 C and those stored at -60 C. The microdilution technique was found to be a highly reproducible method for quantitative determination of antimicrobial susceptibility.

Biological Assay↗

Variation in the susceptibility of strains of Staphylococcus aureus to oxacillin, cephalothin, and gentamicin.

Three cases of staphylococcal bacteremia caused by organisms that were inhibited by low concentrations of oxacillin, but were resistant to the killing effects of oxacillin, stimulated us to screen 60 clinical isolates of Staphylococcus aureus for their susceptibility to oxacillin, cephalothin, and gentamicin. All 60 strains were inhibited by low concentrations of the antibiotics. The antibiotics were bactericidal against 27 of the 60 strains and only bacteriostatic against the other 33 after 24 h of incubation. However, after 48 h of incubation, the antibiotics were also bactericidal against the latter group.

Adolescent↗

[Combination of bacteriostatic and bactericidal drugs: lack of significant in vitro antagonism between penicillin, cephalothin, and rolitetracycline].

Although it is generally believed that bactericidal and bacteriostatic drugs should not be combined in vivo, in vitro experiments using the checkerboard dilution technique revealed no antagonism between penicillin/cephalothin and rolitetracycline but rather additive or synergistic activity of either drug combination in 40 to 50% of 20 Escherichia coli, and 14 Staphylococcus aureus strains. Slight antagonism occurred only between 3 and 8 h after combining penicillin/cephalothin and rolitetracycline in either bacteriostatic or bactericidal concentrations, but not after 24 h of incubation, nor was antagonism found with combinations of these drugs in bacteriostatic concentrations. Neither bacteriostatic nor bactericidal activity of penicillin/cephalothin and rolitetracycline was inhibited by pretreatment of one E. coli strain with bacteriostatic rolitetracycline or bacteriostatic penicillin/cephalothin concentrations. Penicillin and cephalothin could exert a bactericidal effect after 2-h exposure of the E. coli strain to bacteriostatic rolitetracycline concentrations. Combined action of subinhibitory penicillin and rolitetracycline concentrations resulted in more pronounced inhibition of growth than either drug alone. The higher activity of penicillin/cephalothin in combination with rolitetracycline on some E. coli and S. aureus strains might be due to a better access of rolitetracycline into bacterial cells whose cell walls have been weakened by cell wall-active, bactericidal drugs. Thus, growth of penicillin-induced spheroplasts of E. coli and stable staphylococcal L-forms was inhibited by much lower concentrations of rolitetracycline than were the corresponding parent cells with intact cell walls.

Cephalothin↗

Levels of carbenicillin, ticarcillin, cephalothin, cefazolin, cefamandole, gentamicin, tobramycin, and amikacin in human serum and interstitial fluid.

The ability of eight antibiotics (carbenicillin, ticarcillin, cefamandole, cephalothin, cefazolin, gentamicin, tobramycin, and amikacin) to enter human interstitial fluid was evaluated by the skin window technique. All of the antibiotics tested, except cefazolin, which has the highest percentage of protein binding, diffused into the interstitial fluid quite well. This study confirms our previous observation on the effect of high-percentage protein binding on diffusion of a drug into the minimally inflamed extravascular space.

Adult↗

Susceptibility of cephalothin-resistant gram-negative bacilli to piperacillin, cefuroxime, and other selected antibiotics.

The in vitro antibacterial activity of piperacillin and cefuroxime against 180 isolates of cephalothin-resistant Enterobacteriaceae and of piperacillin against 46 isolates of Pseudomonas aeruginosa was determined. Amikacin, gentamicin, carbenicillin, cefoxitin, and cefamandole were included for comparison. The activities of piperacillin and carbenicillin against Enterobacteriaceae were comparable. Piperacillin was appreciably more active against Pseudomonas than carbenicillin and was equivalent in activity to amikacin on a weight basis. The following beta-lactam agents were the most active against the indicated organisms (in parentheses): cefoxitin (indole-positive Proteus spp.), cefuroxime and cefoxitin, (Klebsiella spp.), piperacillin (Enterobacter spp.), cefuroxime and cefoxitin (E. coli), piperacillin and cefoxitin (Serratia spp.), and cefoxitin (Providencia spp.). Amikacin inhibited 98% of Enterobacteriaceae at clinically achievable serum levels.

Amikacin↗

Comparison of cephalothin and cefamandole prophylaxis during insertion of prosthetic heart valves.

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.

Adolescent↗

Susceptibility of Staphylococcus aureus to cefaclor and cephalothin: laboratory and clinical studies.

In vitro susceptibility tests of 201 strains of Staphylococcus aureus by agar dilution revealed 90% to be susceptible to 8 mug or less of cefaclor per ml. Strains from hospitalized children and adults were more often resistant than those from patients with bullous impetigo. Cephalothin was more active than cefaclor against all strains tested. Results with disk tests, including those strains examined from the clinical investigation, revealed some discrepancies in identifying strains more resistant to cefaclor. In clinical studies, cefaclor proved quite effective for the treatment of bullous impetigo. Of 73 patients, 90% were cured and 7% improved after completing 5 or more days of treatment. Prompt improvement was noted among most patients seen 3 to 5 days after treatment was begun. One patient experienced mild diarrhea. There were no other adverse or toxic manifestations attributable to therapy.

Adolescent↗