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PubMed2005

Antimicrobial responses of Yersinia enterocolitica isolates in comparison to other commonly encountered bacteria that causes diarrhoea.

OBJECTIVE: To determine antimicrobial susceptibility and resistance of Yersinia enterocolitica, Shigella, E. coli and Salmonella isolated strains from diarrhoeal out-patients. DESIGN: A cross-sectional study. SETTING: Ethiopian Health and Nutrition Research Institute (EHNRI) in Addis Ababa Ethiopia. SUBJECTS: Fifty one strains of enteric pathogenic bacterial isolates from 205 diarrhoeal out-patient cases. RESULTS: All fifty one strains of enteric pathogenic bacterial isolates were sensitive to nalidixic acid, norfloxacin, and polymyxin B and 46 strains were resistant to cephalothin. Sensitivity to gentamycin, nalidixic acid, norfloxacin and polymyxin B is greater than 90% for the tested strains, while resistance to cephalothin, ampicillin and tetracycline was greater than 50%. All strains of Yersinia enterocolitica were sensitive to carbenicillin, chloramphenicol, gentamycin, kanamycin, nalidixic acid, norfloxacin, polymyxin B, streptomycin, sulphadiazene and trimethoprim-sulphamethoxazole. All strains of Yersinia enterocolitica were resistant to ampicillin. All of the 12 strains of Shigella were sensitive to nalidixic acid, norfloxacin, polymyxin B, gentamycin and kanamycin. Ampicillin, carbenicillin, cephalothin, streptomycin sulphadiazene, tetracycline and trimethoprim-sulphamethoxazole were sensitive against <50% of Shigella isolates. Among the isolates, 91.7% were resistant against tetracycline, 50% against cephlothin, and 75% against each of ampicillin and streptomycin. Totally, ten different patterns of resistance were noted for Shigella spp. All strains of diarrhoeagenic E. coli were sensitive to gentamycin, kanamycin, nalidixic acid, norfloxacin and polymyxin B, while 90.9% of them were sensitive to chloramphenicol. Of all these isolates, 81.8% strains were resistant to cephalothin and 63.6% to sulphadiazene. All Salmonella isolates were sensitive to norfloxacin, polymyxin B and nalidixic acid while 21 (95.5%) of strains were sensitive to gentamycin and kanamycin. Resistance level of 86.4% was found against cephalothin, 36.4% for ampicillin and 27.0% to sulphadiazene and to both streptomycin and trimethoprim-sulphamethoxazole in 22.7% of these strains. Eleven different combinations of resistant patterns were observed for all the Salmonella strains. CONCLUSION: Gentamycin, kanamycin, nalidixic acid, norfloxacin and polymyxin B can be effective in the treatment of diarrhoea due to the enteropathogens.

Anti-Bacterial Agents↗
PubMed1976

Observations in man on some pharmacologic features of cefamandole.

Comparative studies of cefamandole and cephalothin were carried out in 32 cancer patients. After rapid intravenous injection of 1 gm cefamandole or cephalothin, the peak mean serum concentrations in 11 patients achieved at 0.25 hr were 103.4 mcg/ml and 56.7 mcg/ml, respectively. Except at 6 hr, the serum concentration of cefamandole was higher (p less than 0.05) at all times. The terminal half-lives (t 1/2) were similar, being 1.2 hr for cefamandole and 1.0 hr for cephalothin. Cefamandole, 1 gm intramuscularly, induced a peak mean serum concentration of 26.6 mcg/ml at 1 hr, with a slow decay. Intermittent cefamandole (2 gm intravenously every 6 hr) induced very high mean serum concentrations (7 patients), but at 4 hr the concentrations were similar to those after 1 gm intravenously. Per cent of urinary excretion was similar for both drugs regardless of dose and mode of administration. Continuous-infusion cefamandole or cephalothin (2 gm loading followed by 2 gm every 6 hr) in 14 patients showed consistently higher serum concentrations for cefamandole (p less than 0.05) over a 5-day period. There was no evidence of drug accumulation in the multiple-dose studies. Both the single- and multiple-dose schedules were well tolerated.

Adolescent↗
PubMed1990

Antimicrobial prophylaxis for open heart operations.

Between 1986 and 1988, 450 adults undergoing coronary artery bypass, cardiac valve replacement, or both were enrolled into a prospective, randomized, comparative trial of cephalothin versus cefamandole as perioperative prophylaxis. They were assessed during their hospitalization and at 6 weeks and 6 months after discharge for postoperative infectious complications. Eleven patients had major postoperative infections including 5 with sternal wound infections (three bacteremic), 6 with bacteremia, 1 with prosthetic valve endocarditis, and 3 with severe venous donor graft site infections. Eight major infections occurred in patients receiving cephalothin prophylaxis and three in patients receiving cefamandole, with all five sternal wound infections occurring in the cephalothin group. Postoperative pathogens responsible for the major infections included gram-negative aerobes in 5 patients, Staphylococcus aureus in 4, and Staphylococcus epidermidis in 2. Preoperative colonizing staphylococcal isolates were not predictive of postoperative staphylococcal pathogens. Although there was no statistically significant difference in rate of major postoperative infectious complications using either cephalothin or cefamandole prophylaxis, there was a trend in favor of cefamandole. Gram-negative aerobes are becoming increasingly important pathogens in this setting.

Aged↗
PubMed2000

Selective enrichment broth for the isolation of Aeromonas sp. from chicken meat.

Six selective agents (ampicillin, novobiocin, cephalothin, bile salts, brilliant green and ethanol) were tested during the development of a selective enrichment broth for the isolation of Aeromonas sp. from food. Cephalothin at 10 mg/l was found to be the best selective agent owing to its greater selectivity and efficiency in recovering stressed and lower cell concentrations of Aeromonas sp. Higher concentrations (15-25 mg/l) of cephalothin were inhibitory to some strains of A. sobria. Cephalothin (10 mg/l) was incorporated in buffered dextrin broth (BCDB-10) and alkaline peptone water (CAPW-10) and employed for the isolation of Aeromonas sp. from chicken meat naturally and artificially inoculated (with 10(9) cells/ml of A. hydrophila). The highest isolation rate (22%) with naturally contaminated chicken was achieved with CAPW-10 in comparison to 16% with BCDB-10 and 8% with APW. Similarly, from artificially inoculated samples, 100% isolation was accomplished with CAPW-10, against 80% with BCDB-10 and 50% with APW.

Aeromonas↗
PubMed2000

Temperature dependence of bimolecular reactions associated with molecular mobility in lyophilized formulations.

PURPOSE: We studied the temperature dependence of acetyl transfer between aspirin and sulfadiazine, a bimolecular reaction, in lyophilized formulations at temperatures near the glass transition temperature (Tg) and NMR relaxation-based critical mobility temperature (Tmc), to further understand the effect of molecular mobility on chemical degradation rates in solid pharmaceutical formulations. The temperature dependence of the hydrolysis rates of aspirin and cephalothin in lyophilized formulations was also studied as a model of bimolecular reactions in which water is a reactant. METHODS: Degradation of lyophilized aspirin-sulfadiazine formulations containing dextran and various amounts of water at temperatures ranging from 1 degrees C to 80 degrees C was analyzed by HPLC. The degradation of cephalothin in lyophilized formulations containing dextran and methylcellulose was also analyzed at temperatures ranging from 10 degrees C to 70 degrees C. RESULTS: Acetyl transfer in lyophilized aspirin--sulfadiazine formulations containing dextran exhibited a temperature dependence with a distinct break around Tmc, which may be ascribed to a change in the translational mobility of aspirin and sulfadiazine molecules. The hydrolysis of aspirin and cephalothin in lyophilized formulations, which is also a bimolecular reaction, did not show a distinct break, suggesting that water diffusion is not rate-limiting. CONCLUSIONS: The diffusion barrier of water molecules in lyophilized formulations appears to be smaller than the activational barrier of the hydrolysis of aspirin and cephalothin based on the results of this study that the temperature dependence of the hydrolysis rate is almost linear regardless of Tmc and Tg. On the other hand, the diffusion barrier of aspirin and sulfadiazine molecules appears to be comparable to the activational barrier of the acetyl transfer reaction between these compounds, resulting in nonlinear temperature dependence.

Anti-Infective Agents↗
PubMed1993

Evaluation of delayed type hypersensitivity to beta-lactam antibiotics in mice.

This study was designed to determine whether delayed type hypersensitivity could be evoked by protein-unconjugated beta-lactam antibiotics emulsified with Freund's complete adjuvant (FCA) in mice. The method providing the strongest sensitization was assessed by measuring footpad swelling induced by several biweekly intervals of subcutaneous injections of 0.8 mg/mouse cephalothin with FCA, followed by intradermal challenge with 1.0 mg/site cephalothin into the footpad in four different strains of female mice. A total of three and four injections, once every two weeks, in BDF1 and DBA/2 mice, respectively, produced the greatest potential for swelling. This swelling could be reinduced by the local passive transfer of cephalothin-primed splenocytes into the footpad of naive recipient mice. Moreover, the reaction was diminished by the addition of anti-Thy-1.2 monoclonal antibody with low-toxicity rabbit complement to cephalothin-primed splenocytes. Swelling in the footpad was therefore induced via the delayed type hypersensitivity reaction, indicating T-lymphocyte dependence. When the potential for beta-lactam antibiotics to elicit delayed type hypersensitivity was investigated in BDF1 mice, eight of the nine agents employed showed a 10-90% positive incidence. This result had a significant correlation (r = 0.76) with the data for skin reaction in guinea pigs, the method generally used for estimating allergenicity. These results suggest that this procedure may be a useful tool for evaluating delayed type hypersensitivity induction during the early development of novel antibiotics, since not only can sensitization be induced with protein-unconjugated antibiotic, but also because assessment can be made using a small amount of sample.

Animals↗
PubMed1975

Antibiotics in human hematoma and wound fluid.

Using the total hip replacement patient, we measured the level of antibiotic in the wound at the time of surgery, the wound drainage for 36 to 48 hours after surgery and over a 10 day period in incubated surgical debris obtained at the time of total hip replacement. The antibiotics sodium oxacillin, lincomycin hydrochloride and sodium cephalothin were administered in standard doses at 6 hour intervals. In one group of patients the antibiotic was begun at the time of surgery, in a second group the antibiotic was begun 24 hours after the completion of surgery. Sodium oxacillin, lincomycin hydrochloride and sodium cephalothin produce antibiotic levels in the venous serum consistently above the level obtained in the simultaneous would drainage specimens. Sodium oxacillin and lincomycin hydrochloride used as described in this study are capable of bathing the area of the surgical wound with concentrations of antibiotics above the minimal inhibitory concentrations. This is evidenced by the antibiotic levels above minimal inhibitory concentrations found in the wound drainage. Sodium cephalothin levels in the wound drainage were below measurable levels in 3 of 4 patients. Sodium oxacillin and lincomycin hydrochloride antibiotic levels in the surgical wound debris and simultaneous venous clotted specimens diminished progressively in a similiar manner indicating no additional effects of the surgical wound debris on the antibiotic's biologic effectiveness. Sodium cephalothin dropped below measurable levels in three days. Measurable levels of antibiotics appeared in the wound aspirate well above the minimal inhibitory concentration in patients receiving their initial dose of sodium oxacillin 24 hours after surgery.

Anti-Bacterial Agents↗
PubMed1976

Antibiotic synergy and antagonism against clinical isolates of Klebsiella species.

Minimal inhibitory concentrations of kanamycin, gentamicin, amikacin, cephalothin, and chloramphenicol were determined in Trypticase soy broth for 70 clinical isolates of Klebsiella species. Gentamicin and amikacin were the most active on a weight basis. Chloramphenicol was more active than kanamycin, and cephalothin was the least active of all. Studies using a microtiter modification of the checkerboard technique were performed to evaluate the comparative activity of the three aminoglycosides in combination with either chloramphenicol or cephalothin. The cephalothin-aminoglycoside combinations demonstrated synergy in >80% of the isolates tested. No antagonism was noted. The chloramphenicol-aminoglycoside combinations showed antagonism in 35 to 45% of the isolates tested. The data suggest that the chloramphenicol-aminoglycoside combinations be used with caution when treating serious infections where Klebsiella is a potential pathogen.

Aminoglycosides↗
PubMed1987

Cephalosporin susceptibility of methicillin-resistant, coagulase-negative staphylococci.

Coagulase-negative staphylococci were tested for susceptibility to methicillin, cephradine, ceftriaxone, cephalothin, and cefamandole by standard broth microdilution. Most of the 26 methicillin-resistant isolates were susceptible to cephalothin and cefamandole, but very few were susceptible to ceftriaxone, and none was susceptible to cephradine. The proportion of bacterial cells that grew in the presence of 128 micrograms of methicillin per ml was calculated for each methicillin-resistant isolate. Those with every cell or 1 in 10 cells resistant to 128 micrograms of methicillin per ml included the isolates that were most resistant to the cephalosporins and highly resistant to methicillin. Those with 1 cell resistant in 10(5) or 10(6) cells were the isolates most susceptible to the cephalosporins, and their methicillin MICs were lower. When cells resistant to 128 micrograms of methicillin per ml were used as inocula for broth microdilution tests, resistance to cephradine remained the same, but resistance to ceftriaxone, cephalothin, and cefamandole increased significantly. Cefamandole was the only cephalosporin which retained antibacterial activity against some methicillin-resistant isolates (12 of 26). Cephradine, ceftriaxone, cephalothin, and cefamandole resistance appeared to be expressed by the same cells that expressed methicillin resistance. In this way, cross resistance was demonstrated between methicillin and the cephalosporins.

Cefamandole↗
PubMed1988

Monitoring beta-lactamase activity in vivo by 13C nuclear magnetic resonance spectroscopy.

A 13C-labeled cephalothin, 7 beta-(2-thienylacetamido)-3-[acetoxy-13C1]methyl-3-cephem-4- carboxylate (compound 1), has been prepared and used to monitor beta-lactamase activities by 13C nuclear magnetic resonance spectroscopy. Time-elapsed spectral analysis of the reaction of the labeled cephalothin with the TEM-2 beta-lactamase purified from Escherichia coli revealed the progressive loss of the cephalothin acetyl resonance at 176.8 ppm and accumulation of an acetate signal at 184.3 ppm. Spectral results identical to those observed in the in vitro experiment were obtained when compound 1 was incubated with cell suspensions of E. coli JSR-O (pBR322), which contains the plasmid-encoded TEM-2 beta-lactamase, and Enterobacter cloacae strains that contain a class I chromosomal beta-lactamase. Pseudo-first-order rate constants for the lactamase-catalyzed formation of acetate from cephalothin in vivo were obtained by integration of the 13C-acetyl resonances of compound 1 during timed incubations with cell preparations. These results constitute the first demonstration of the ability to monitor beta-lactamase activity in viable cells by nuclear magnetic resonance spectroscopy.

Cephalothin↗
PubMed1975

In vitro activity and pharmacokinetics in patients of cefamandole, a new cephalsoporin antibiotic.

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Cefamandole was more active than cephalothin or cefazolin against Proteus mirabilis. Both cefamandole and cefazolin were as active as cephalothin against S. aureus, were slightly more active against K. pneumoniae, and were considerably more active against E. coli. All strains of indole-positive Proteus sp. were inhibited by 6.3 mug of cefamandole per ml but only 20% were inhibited by 25 mug of cefazolin or cephalothin per ml. Eighty-eight percent of Enterobacter sp. was inhibited by 25 mug of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 mug/ml in serum and levels ranged from 440 to 16,800 mug/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of >/=31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was >/=43%. The half-life of cefamandole in serum was 49 to 126 min.

Bacteria↗
PubMed1986

Relationship of shape to initiation of new sites of envelope growth in Streptococcus faecium cells treated with beta-lactam antibiotics.

Exponential-phase cells of Streptococcus faecium were treated with concentrations of ampicillin and cephalothin which, over 60 min, had little effect on increase in culture mass but resulted in about a 65% inhibition of increase in cell numbers. The resulting drug-treated cells underwent about a doubling in cell mass and volume above that of the untreated cells. The newly divided cells produced in the presence of drugs were shown to be due to the division of central or primary sites of envelope growth present at the time of treatment. Sites that were newly initiated (secondary sites) at the time of treatment or sites initiated after treatment did not divide but enlarged in length and girth to give abnormally large cells. Although the increase in average total volume was the same after each interval of treatment with ampicillin and cephalothin, the primary growth sites of the cephalothin-treated cells grew somewhat more slowly, and their secondary sites grew somewhat more quickly, than did those of the ampicillin-treated cells. Cephalothin-treated cells initiated secondary sites at a rate similar to that of the untreated cells, whereas the ampicillin-treated cells exhibited reduced rates of secondary site initiation. Two models are presented that account for these results.

Ampicillin↗
PubMed1964

Influence of antibiotic stability on the results of in vitro testing procedures.

Wick, Warren E. (The Lilly Research Laboratories, Indianapolis, Ind.). Influence of antibiotic stability on the results of in vitro testing procedures. J. Bacteriol. 87:1162-1170. 1964.-Certain antibiotics undergo at least partial degradation under the conditions of in vitro testing procedures. With cephalothin used as an example, experimental evidence is presented to indicate the necessity for re-evaluation of results obtained from in vitro sensitivity testing methods for some antibiotics. The in vitro activity of cephalothin, tetracycline, and chloramphenicol against a variety of gram-negative bacteria is described. Plate counts demonstrate changes in the viable cell population over a 48-hr period in tubes of minimal inhibitory concentration (MIC) tests, with an abrupt rise in MIC value for cephalothin between the 12th and 24th hr. Data obtained by chromatographic methods, showing the degradation of cephalothin for the same time interval, indicated that instability of the antibiotic between the 12th and 24th hr might adversely affect the results obtained from standard 20- to 24-hr in vitro antibiotic sensitivity testing methods. Because repeated administration of an antibiotic to a patient at 4- to 8-hr intervals reinforces the original concentration, a more accurate estimate of antibacterial activity of that antibiotic might preferably be related to this time interval.

Cephalothin↗
PubMed1976

[The cephalosporins and their clinical value].

Up to now cephalothin was the only parenteral and cephalexin the only oral cephalosporin for clinical use in the GDR. The paper deals with several newer cephalosporins. Of these cephazolin shows some advantages, especially in antibacterial activity and serum levels. There is no metabolization and a better local tolerability compared with cephalothin. Cephapirin has no and cephacetril only inessential advantages. The antibacterial activity of the also well tolerated cephradin is less than that of cephalothin. Certain favourable pharmacokinetic properties such as high lymph and tissue levels, related to serum levels, slight protein binding, high distribution volume and a better stability against beta-lactamases lead to a superiority over cephalothin and diminish the disadvantages compared with cephazolin. The oral form of cephradin very equals to cephalexin.

Abortion, Septic↗
PubMed1981

Susceptibility of clinical strains of bacteria to cefoxitin.

The susceptibility of 3044 bacterial strains isolated from patients at Auckland Hospital were tested by the disc diffusion of cefoxitin, cephalothin and ampicillin. 86.5 percent of these strains were sensitive to cefoxitin, 71.3 percent sensitive to cephalothin and 41.6 percent ot ampicillin. A significant difference between cefoxitin and cephalothin was observed with E. coli, Klebsiella, Enterobacter and Proteus species. S. epidermidis alone showed significantly less strains susceptible to cefoxitin than cephalothin.

Ampicillin↗
PubMed1982

Accuracy and efficiency of three methods of preparing piggyback admixtures.

The efficiency and accuracy of three methods of preparing i.v. admixtures in small-volume plastic bags were compared. One hundred individual 1-g doses of cephalothin sodium in 50-ml minibags were prepared by each of three methods; the PharmAide Fluid Dispensing System (PAFDS), the Valleylab IV Formulator, and the Viavac vacuum unit, using 20-g, 20-g, and 1-g vials of cephalothin sodium, respectively. For each method, preparation time and cost were recorded. To determine accuracy, a random 10% sample of minibags prepared by each method was assayed for cephalothin concentration by microbiologic assay. The IV Formulator required the least time to prepare 100 doses, followed by the PAFDS and the vacuum unit. Cost data for the three methods were nearly identical, with a difference of only $0.07 per dose between the least and most expensive. The minibags prepared using the vacuum pump and unit-of-use vials were more accurate than those prepared with 20-g vials and the other two methods. However, the initial concentration of the cephalothin sodium vials before transferring to the minibags was not tested. Each method studied was found to have advantages and disadvantages. No one system could be judged best for all situations.

Cephalothin↗
PubMed1980

Prophylactic antibiotics in hip fractures. A double-blind, prospective study.

Three hundred and seven patients, each of whom had a fracture of the proximal part of the femur, were studied in a randomized, double-blind fashion to determine whether perioperative administration of cephalothin would prevent postoperative infection. Major postoperative wound infections were significantly reduced in the cephalothin-treated group (4.7 per cent versus 0.7 per cent; p less than 0.05). There also was a reduction in the incidence of postoperative urinary-tract infections and a reduction in mean peak body temperatures. The duration of hospitalization was not affected and no hospital stay was prolonged by complications of antibiotic administration. However, in the cephalothin-treated group, a strong trend toward colonization by cephalothin-resistant organisms was noted.

Adolescent↗
PubMed1976

A rationale for intraperitoneally administered antibiotic therapy.

A satisfactory clinical response occurred in 96.7 per cent of 210 patients with proved bacterial peritonitis following appropriate surgical intervention and an antimicrobial regimen of 1 per cent cephalothin administered intraperitoneally, with supplementary antibiotics as indicated. Instillation of cephalothin achieves the therapeutic benefits of high intraperitoneal levels with an antibiotic of broad activity and minimum toxicity and permits flexibility in the choice of additional antimicrobial therapy. Adjuvant therapy with cephalothin did not result in peritoneal adhesions or significant abdominal pain. Clinical experience suggests that it may promote healing of anastomotic leaks. The results of this study indicate that intraperitoneally administered cephalothin is a significant factor in lowering the death rate in peritonitis.

Cephalothin↗