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PubMed1981

Antibacterial activity of five cephalosporins.

The in vitro susceptibilities of 7 commonly isolated species of bacteria to cephalothin, cefoxitin, and 3 new cephalosporins--cephamandole, cefuroxime, and cefoperazone--were studied using an agar dilution method. Cephalothin and cephamandole were the most active agents against staphylococci. Against members of the Enterobacteriaceae all the newer agents were more active than cephalothin; however, important individual differences emerged. Only cefoperazone had significant activity against Pseudomonas aeruginosa.

Bacteria↗
PubMed2003

Enterococcus faecalis and Enterococcus faecium isolates from milk, beef, and chicken and their antibiotic resistance.

The occurrence and antibiotic resistance of enterococci, especially Enterococcus faecalis and Enterococcus faecium, in milk, beef, and chicken in Gaborone, Botswana, were studied. Enterococci were isolated from these sources with the use of bile esculin agar and identified with API 20 Strep kits. Antibiotic resistance was determined by the disk diffusion method. The antibiotics tested were vancomycin, teicoplanin, ampicillin, tetracycline, and cephalothin. Among the 1,467 enterococci isolated from the samples, E. faecalis (46.1%) and E. faecium (29.0%) were found to be the predominant species. Other enterococcal species made up 25% of the isolates. More than 96 and 97% of the E. faecalis and E. faecium isolates, respectively, were found to be resistant to ampicillin. Almost 34, 27.3, and 22.4% of the E. faecalis isolates from milk, beef, and chicken, respectively, were also resistant to cephalothin. The percentages of E. faecium isolates that were found to be resistant to cephalothin were 32.8, 16.9, and 17.3% for milk, beef, and chicken, respectively. Resistance to vancomycin was widespread. It was found that 18.8, 7.8. and 13.1% of the E. faecalis isolates from milk, beef, and chicken samples, respectively, were resistant to vancomycin. In contrast, 32.8, 24.7, and 30.7% of the E. faecium isolates from milk, beef, and chicken samples, respectively, were resistant to vancomycin. Isolates that were resistant to multiple drugs were found in relatively large numbers.

Ampicillin↗
PubMed1978

Cefazolin.

After 5 years of use, cefazolin can be considered similar to cephalothin as a therapeutic agent and in its potential for adverse reactions. When cefazolin and cephalothin are compared by appropriately designed clinical trials, neither cefazolin's slightly greater in-vitro susceptibility to staphylococcal beta-lactamase inactivation, nor its slightly greater microbiologic activity for some enterobacteraciae has been shown to result in any readily apparent therapeutic differences. The important differences between cefazolin and cephalothin--and this is also probably true with respect to cephapirin and cephradine--are not in therapeutic effectiveness, microbiologic activity, or toxicity but rather in pharmacokinetics and cost-effectiveness.

Agranulocytosis↗
PubMed1979

[Prophylactic use of antibiotics in biliary tract and stomach surgery (author's transl)].

115 patients undergoing elective surgery on biliary tract (80 patients), and stomach (35 patients) for duodenal ulcer were divided into three groups: some received prophylactic antibiotics, cephalothin sodium or sulfamethoxazole trimethoprim and some received none. The antibiotics were started preoperatively and continued postoperatively for three days. The wound infection rate was reduced from 7.1% in the control group to 2.3% in patients treated with cephalothin sodium and 3.2% in sulfamethoxazole trimethoprim treated group. In patients who had biliary tract surgery, the wound infection rate was reduced to 3.3% and 0% with cephalothin sodium and sulfamethoxasole-trimetoprim respectively from 10% in the control group. Only one patient who had gastric surgery who received sulfamethoxasole-trimetoprim prophylactically, developed wound infection postoperatively. The difference between the groups was not statistically significant (p > 0.05). However the wound infection rate was higher in patients who had positive bile culture (p < 0.05).

Anti-Bacterial Agents↗
PubMed1991

The antibacterial activity of a siderophore. 2. The influence of deferoxamine alone and combined with ascorbic acid on the activity of antibiotics against Staphylococcus aureus.

The in vitro activity of deferoxamine (DFO) combined with cephalothin, gentamicin, cefotaxime, vancomycin, and fusidic acid, in the presence or absence of the reductant ascorbic acid (AA) was investigated against Staphylococcus aureus by a macrobroth dilution technique and killing curve kinetics. DFO and in particular DFO + AA lowered the MICs of cephalothin, gentamicin, cefotaxime, and fusidic acid for most of the strains and in some instances also the MICs of vancomycin. To characterize the interaction between DFO or DFO + AA and antimicrobials we applied the growth constants of logarithmic growth phase. Generally DFO acted synergistically with cephalothin, gentamicin, vancomycin, and fusidic acid, particularly in the presence of AA, and in some cases synergy was demonstrated with cefotaxime, too.

Anti-Bacterial Agents↗
PubMed1978

Clostridial myonecrosis ('gas gangrene') during cephalosporin prophylaxis.

Four cases of clostridial myonecrosis that developed in open fractures were treated with surgical debridement and with intravenous cephalosporins as antibiotic prophylaxis. All patients recovered following amputation of the involved extremity, and treatment with high-dose penicillin in three cases, and erythromycin plus high-dose cephalothin in the fourth. This complication was not seen in patients with similar injuries that were managed surgically but used other antibiotics, usually penicillin, as prophylaxis. In vitro susceptibility tests of clostridia to cephalothin were performed; the results demonstrated that nearly 50% of clostridia tested were resistant to cephalothin.

Adult↗
PubMed1985

Effect of cephalosporins on organic ion transport in renal membrane vesicles from rat and rabbit kidney cortex.

The effects of cephaloridine and cephalothin on prototypical organic anion (p-aminohippurate, PAH) and cation (N-methylnicotinamide, NMN) transport were observed in brush border and basolateral membrane vesicles prepared from rat and rabbit renal cortex. The cephalosporins interacted with both the cationic and anionic transport systems. Cephalothin inhibited PAH transport in basolateral and brush border membrane in both rats and rabbits. Cephaloridine on the other hand inhibited PAH and NMN transport across rabbit basolateral membranes while it showed a lack of interaction with transport systems in rat basolateral membranes. Conversely, cephaloridine inhibited brush border transport of PAH and NMN in the rat but not in the rabbit. These results provide indirect evidence that cephalothin may be secreted across the renal tubule cell in rats and rabbits while cephaloridine may not accumulate in the rat kidney and becomes trapped in rabbit renal tubule cells. The differences in transport effects observed may explain intra- and interspecies differences in susceptibility to cephalosporin nephrotoxicity.

Alkaline Phosphatase↗
PubMedDate not supplied

Synergy of vancomycin with penicillins and cephalosporins against pseudomonas, klebsiella, and serratia.

A model of antibiotic synergy based on a molecular mechanism of action which blocked sequential steps in a single metabolic pathway was tested. Twenty-five strains each of Pseudomonas, Klebsiella, and Serratia were tested in vitro against three different two drug combinations of vancomycin, carbenicillin, or cephalothin. Synergy was observed when vancomycin was combined with either carbenicillin or cephalothin against isolates of Pseudomonas or Serratia, whereas the combination of carbenicillin and cephalothin did not result in significant synergy against these isolates. The presence of synergy was not related to the sensitivity or resistance of the isolates to the drugs in the combination. Synergy was also observed with all three antibiotic combinations against Klebsiella isolates which may be related to enzyme inactivation by one of the drugs in the combination. These observations support the hypothetical model of antibiotic synergy based on sequential blocking of one biochemical pathway.

Carbenicillin↗
PubMed1979

Clinical and laboratory studies with cefaclor: efficacy in skin and soft tissue infections.

Clinically relevant, recent isolates of common Gram-positive pathogens were examined for their in vitro susceptibility to cefaclor. Group A streptococci and pneumococci were uniformly sensitive (MICs 0.06--0.12 micrograms/ml) to both cefaclor and cephalothin. Cefaclor was 5--10-fold less active than cephalothin against group B streptococci. S. aureus strains were uniformly more susceptible to cephalothin than to cefaclor, but among isolates from children, almost all were sensitive to the latter drug. In clinical studies of patients with skin and soft tissue infections, cefaclor proved effective. Over 90% of patients with staphylococcal bullous impetigo, streptococcal and mixed streptococcal-staphylococcal forms of pyoderma were cleared after 7--10 day courses of treatment. In addition, twice-daily therapy, examined more recently, proved as effective in these forms of infection as did the conventional dose schedule. No significant adverse reactions were noted. Cefaclor appears to be an effective orally absorbed cephalosporin for common skin and soft tissue infections.

Adolescent↗
PubMedDate not supplied

In vitro antibacterial activity of a new 1-oxa cephalosporin compound.

The in vitro activity of a unique new 1-oxa cephalosporin beta-lactam antibiotic (LY 127935) was tested against clinical isolates of gram-positive and gram-negative bacteria and compared with the activities of cefoxitin, cefamandole, cephalothin, clindamycin, amikacin, tobramycin, gentamicin, ticarcillin, and carbenicillin. The new compound was observed to have a broad spectrum of antibacterial activity which far exceeded the activity of older cephalosporins against aerobic gram-negative enteric bacilli. This new compound was the most active drug tested against Klebsiella, Serratia, Enterobacter, indole-negative and positive Proteus species, and E. coli. Against clinical isolates of Pseudomonas species the new compound was more active than cefoxitin, cefamandole, cephalothin, and clindamycin, comparable to ticarcillin and carbenicillin, and less active than gentamicin, tobramycin, and amikacin. Yet, most of the Pseudomonas isolates were inhibited by 16 micrograms/ml of the new compound. Against both beta-lactamase and non beta-lactamase producing Staphylococcus aureus isolates, the new 1-oxa compound was less active than the older cephalosporins of which cephalothin and cefamandole were the most effective. The 1-oxa compound had no appreciable activity against isolates of Streptococcus faecalis. Activity of all four cephalosporins studied was decreased in the presence of an increased inoculum of Enterobacteriaceae in trypticase soy and Mueller-Hinton broth. The activity of the new compound against Pseudomonas species was also decreased by an increased inoculum in Mueller-Hinton but not in trypticase soy broth. These results indicate that this new 1-oxa compound may have great promise as a broad spectrum antibiotic and may warrant controlled clinical trials in man.

Amikacin↗
PubMed1982

Therapy of methicillin-resistant Staphylococcus epidermidis experimental endocarditis.

Antibiotic therapy of methicillin-resistant Staphylococcus epidermidis endocarditis was investigated with the rabbit endocarditis model. Time-kill studies in vitro demonstrated that gentamicin and rifampin had the most rapid early bactericidal rates. With rifampin alone, rifampin-resistant subpopulations emerged. Combinations of antibiotics with gentamicin or rifampin in vitro did not significantly alter the killing rate but prevented emergence of subpopulations resistant to the latter. In the rabbit endocarditis model, gentamicin and vancomycin were the most effective single antibiotic regimens in terms of ability to reduce the bacterial densities on cardiac valve vegetations. Five treatment regimens were equally effective, including vancomycin, gentamicin, vancomycin plus rifampin or gentamicin, and rifampin plus gentamicin. The three-drug combination of vancomycin, rifampin, and gentamicin did not significantly improve the results. Cephalothin therapy was significantly less effective than any of the regimens noted above. It was no more effective than no treatment at 2 days and was only slightly more effective at 4 days. This result with cephalothin treatment was not predicted by routine types of in vitro antibiotic susceptibility testing. Treatment of rabbits with methicillin or cephalothin was associated with an increase in the subpopulation of bacteria resistant to the respective drugs. A number of regimens show potential for therapy of these infections, including vancomycin plus rifampin or gentamicin, rifampin plus gentamicin, and vancomycin alone.

Animals↗
PubMed1981

[Influence of antibiotics on the phagocytosis of Klebsiella pneumoniae by alveolar macrophages (author's transl)].

The effect of gentamicin and cephalothin on the phagocytosis of Klebsiella pneumoniae by alveolar macrophages of guinea pigs was tested. At their minimal bactericidal concentration (MBC) the antibiotics did not influence the uptake of bacteria by macrophages in the presence of various antibody titers. As expected, the number of surviving bacteria after intracellular ingestion decreased at MBC of the antibiotics. The uptake of bacteria was inhibited by very high concentrations of gentamicin and cephalothin only. The intracellular killing of the bacteria was already higher in the presence of relatively low antibiotic concentrations (one third of the minimal inhibitory concentration, MIC) as compared to the killing without antibiotics. Above this levels, even if they were considerably higher than the MIC, the antibiotics had no additional effect on the number of bacteria surviving after ingestion. These findings indicate that concentrations above one third of the MIC of gentamicin or cephalothin are not necessarily of advantage for the effect of macrophages on the bacteria, provided that sufficient levels of antibodies are also present.

Animals↗
PubMed1978

Antibiotics in acute cholecystitis.

In 460 cholecystectomies performed for acute cholecystitis 215 (47%) positive gallbladder bile cultures were obtained. In 73% of emergency operations bacteria were recovered, in 48% of early operations (p less than 0.001) and in 29% of late operations (p less than 0.001). In vitro concentrations of 8-16 mcg/ml of ampicillin or cephalothin inhibited in most cases the growth of E. coli, Klebsiella and Enterococci, which comprised 75% of all strains isolated. One hour after intravenous infusion of 1 g ampicillin the mean serum level was 21 mcg/ml, the mean common duct level 16 mcg/ml and the mean gallbladder bile level 4.4 mcg/ml. In acute cholecystitis 2 g cephalothin gave mean concentrations of 14, 8, and 1.2 mcg/ml. Most of these patients had cystic duct obstruction both on intravenous cholegraphy and during operation. Control patients with patent cystic ducts who received ampicillin had mean gallbladder and common duct bile levels of 47 and 56 mcg/ml, and those receiving cephalothin 23 and 28 mcg/ml. It appears that adequate gallbladder bile concentrations of antibiotics are not attainable in acute cholecystitis because of the obstruction to the bile flow. The favourable results of prophylactic antibiotic treatment in reducing septic complications seem to depend more on adequate serum and tissue concentrations than on the concentration of antibiotics in the bile.

Acute Disease↗
PubMed1994

The antibacterial activity of a siderophore. 3. The activity of deferoxamine in vitro and its influence on the effect of antibiotics against Escherichia coli, Proteus mirabilis and coagulase-negative staphylococci.

The in vitro activity of deferoxamine (DFO) both per se and in combination with the reductant ascorbic acid (AA) was determined against 10 E. coli strains, 5 P. mirabilis strains, and 10 coagulase-negative staphylococci. In terms of interaction, the influence of DFO on the activities of cephalothin and gentamicin was furthermore investigated against the same panel of strains employing a macrobroth dilution technique and killing-curve kinetics. The MICs of cephalothin and gentamicin were lowered for one half of the strains. Moreover, DFO prolonged the generation times of logarithmic growth phase considerably, especially when the reductant AA was present. The interactions between DFO or DFO+AA and subinhibitory concentrations of antibiotics were established by the application of growth constants, and resulted in synergy for 15 out of 25 strains with cephalothin and 9 out of 25 strains with gentamicin.

Anti-Bacterial Agents↗
PubMed1993

[Peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Evaluation of cephalothin/cephalexin monotherapy as initial treatment].

To evaluate the initial antibiotic regime of cephalothin monotherapy in the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD), the frequency of peritonitis was registered retrospectively together with the frequency of recurrent episodes and change of antibiotic. A median frequency of 0.96 episodes per year of dialysis was found. In 24% of the episodes no microorganism was cultured. 82% of the microorganisms were gram-positive cocci, 17% gram-negative rods. The frequency of recurrent episodes was 7%. The initial antibiotic treatment with cephalothin had to be changed in 33% of the cases due to microbial resistance. In another 33% the antibiotic treatment was changed to something with a narrower spectrum. More than one third of the resistant microorganisms were methicillin-resistant coagulase-negative staphylococci. With quick and reliable microbiological diagnostic technique that makes it possible to change the antibiotic treatment early, we find cephalothin to be a suitable initial monotherapy.

Adolescent↗
PubMed1979

Penicillin and cephalosporin immunogenicity in man.

Whether cross-allergenicity exists between the penicillin and cephalosporin antibiotics is controversial. A solid-phase radioimmunoassay was adapted to detect drug-specific IgG, IgM and IgE antibodies. Penicillin and cephalothin-specific serum immunoglobulins were determined in patients' serum before and after a therapeutic course of sodium cephalothin. Changes in IgG, IgM and IgE antipenicillin and anticephalothin antibodies, respectively, occurred and were closely correlated to one another (r = 0.80--0.99, p less than 0.0005), indicating that antibody responses to penicillin and cephalothin were linked. This in vitro assay system should prove useful for further study of clinical drug allergies.

Animals↗
PubMed1978

The activity of cephalosporins on beta-lactamase-producing Neisseria gonorrhoeae.

The antibacterial activity of cephaloridine, cephalothin, cephalexin, cephradine, cefazolin, cefamandole, cefuroxime and cefoxitin was determined for six beta-lactamase-producing gonococci isolated in Great Britain and the USA. Cefuroxime was most active against small and large inocula, then cefoxitin, while cephaloridine was least active. Cefamandole was more active than cefazolin and cephalothin, but only on small inocula, and these three antibiotics, with the slightly inferior cephalexin and cephradine, all had moderate activity against large inocula. The inoculum effect (or lack of it) with cephaloridine, cefamandole, cefoxitin, and possibly cefazolin and cephalothin, may be explicable in terms of the level of their susceptibility to enzymic degradation, but this appears not to be true of the inoculum effect with cefuroxime, cephalexin and cephradine. The enzymes from the various strains had closely similar isoelectric points, apparently the same as that for TEM I from E. coli.

Amidohydrolases↗
PubMed1986

Cephalosporin therapy for salmonellosis. Questions of efficacy and cross resistance with ampicillin.

The new cephalosporins should be explored for Salmonella septicemia efficacy, because of multiple-drug resistance, the high incidence of patient allergies to ampicillin and sulfamethoxazole-trimethoprim, and the limited number of antibiotics with proven efficacy. This study reports on six widely used cephalosporins: cephalothin, cefamandole, cefoperazone, cefoxitin, cefotaxime, and ceftriaxone with respect to in vitro killing of Salmonella. This in vitro activity was related to the stability of the agents to beta-lactamases. Cefoperazone was the least stable, followed by cefamandole and cephalothin. Cefoxitin, cefotaxime, and ceftriaxone were the most stable. The beta-lactamase-unstable agents permitted regrowth of beta-lactamase-producing salmonella within 36 hours. Standard susceptibility tests showed good inhibitory levels by these unstable agents at 18 hours, but the minimum inhibitory concentrations increased dramatically with longer incubation periods. Based on these results, past cephalothin failures for ampicillin-resistant Salmonella can be explained. Additionally, there should be a dichotomy of effectiveness in the new cephalosporins depending on their beta-lactamase stability. The stable cephalosporins deserve further clinical trials in the treatment of beta-lactamase-producing Salmonella infections.

Ampicillin↗