Comparison of cefazolin, a new cephalosporin antibiotic, with cephalothin.
Resistance to cephalothin was associated in general with a lack of susceptibility to cefazolin, a new 7-amino cephalosporanic acid derivative.
Cephalosporins↗
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Influence of subinhibitory concentrations of penicillin, cephalothin, and clindamycin on Staphylococcus aureus growth in human phagocytic cells.
After an initial 2-h incubation with phagocytic cells, the growth of surviving intracellular Staphylococcus aureus was examined in the presence of subinhibitory concentrations of penicillin, cephalothin, and clindamycin. One-tenth of the minimal inhibitory concentrations of these antibiotics markedly reduced bacterial growth in normal polymorphonuclear leukocytes. In contrast, when human alveolar macrophages were studied, no inhibition of growth was seen. Subinhibitory concentrations of these antibiotics and polymorphonuclear leukocytes acted synergistically to reduce intracellular survival of S. aureus. This synergy did not appear to be dependent upon the microbicidal potential of the leukocyte respiratory burst, since no differences were found when polymorphonuclear leukocytes obtained from patients with chronic granulomatous disease were compared with those from normal donors.
Cephalothin↗
Enhanced in vitro bactericidal activity of amikacin or gentamicin combined with three new extended-spectrum cephalosporins against cephalothin-resistant members of the family Enterobacteriaceae.
The in vitro bactericidal interactions of three new extended-spectrum cephalosporins (ceftriaxone, ceftizoxime, or ceftazidime) in combination with gentamicin or amikacin were compared against 40 recent nosocomial bloodstream Enterobacteriaceae isolates by the timed-kill curve technique. All of the study strains were cephalothin resistant, and 56% were resistant to cefamandole. Combinations of aminoglycosides plus ceftriaxone or ceftizoxime exhibited an enhanced bactericidal effect with the highest frequency (approximately 85 to 90%), whereas gentamicin-ceftazidime combinations demonstrated the lowest frequency (for 60% of assays, P less than 0.0005 against the nonceftazidime regimens). The enhanced bactericidal effects occurred within readily achievable drug levels in serum for all of the single antibiotic constituents. No bactericidal antagonism was observed. There was no discernible relationship between the relative in vitro susceptibilities of the 40 study isolates to ceftazidime and the potential for gentamicin-ceftazidime combinations to demonstrate enhanced bactericidal activity. In 14 of the 40 study strains (35%) all six drug combinations tested demonstrated an enhanced bactericidal effect. In nearly 50% of bactericidal interactions which resulted in enhanced bactericidal effect at 24 h, such enhanced killing was clearly demonstrable by 4 h of incubation. These results delineate a frequent and rapid enhancement of in vitro bactericidal activity between three new extended-spectra cephalosporins and aminoglycosides against nosocomial members of the family Enterobacteriaeceae.
Amikacin↗
Double-blind controlled comparison of phlebitis produced by cephapirin and cephalothin.
In a double-blind study with each patient as his own control cephapirin and cephalothin were administered to 20 patients in opposite arms for a period of 48 hr each. Neither the incidence of phlebitis nor the degree of phlebitis was significantly different with the two drugs, and there was no difference in the time of onset of pain or phlebitis.
Adult↗
Randomized comparison between two ceftazidime-containing regimens and cephalothin-gentamicin-carbenicillin in febrile granulocytopenic cancer patients.
Because the results of our published trial [R. Ramphal, B. S. Kramer, K. H. Rand, R. S. Weiner, and J. W. Shands, Jr., J. Antimicrob. Chemother. 12(Suppl. A):81-88, 1983] of ceftazidime versus cephalothin, gentamicin, and carbenicillin (KGC) revealed a preponderance of gram-positive superinfections, including those caused by clostridia, in patients treated with ceftazidime, we added vancomycin to the ceftazidime regimen at study entry 49 and continued with a 2:1 randomized comparison of ceftazidime-vancomycin (CV) versus KGC. Criteria for study entry were fever (temperature, greater than or equal to 38.5 degrees C on one occasion or greater than or equal to 38 degrees C on two occasions 6 h apart) and granulocytopenia (less than 500/mm3 or a falling count anticipated to be less than 500/mm3). Ninety-five entries (79 patients) were evaluable. The numbers of initial clinical responses for ceftazidime-, KGC-, and CV-treated patients were 9 of 21 (43%), 21 of 37 (57%), and 21 of 37 (57%), respectively; differences were not significant. The death rate was lower with CV (2 of 37 patients) than with KGC (10 of 37 patients) (P less than 0.05 by two-tailed analysis) or with ceftazidime alone (7 of 21 patients) (P less than 0.025). Death from presumed infections occurred in 9 of 37 KGC-treated patients versus 1 of 37 CV-treated patients (P less than 0.025). Superinfections occurred in five ceftazidime-treated patients (24%) versus 7 KGC-treated patients (19%) but not in CV-treated patients (CV versus KGC, P less than 0.05; CV versus ceftazidime, P less than 0.01). CV appears to be superior to KGC or ceftazidime alone in the management of febrile granulocytopenic cancer patients.
Adult↗
Presence of an additional penicillin-binding protein in methicillin-resistant Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus simulans with a low affinity for methicillin, cephalothin, and cefamandole.
The presence of an additional penicillin-binding protein (PBP) was demonstrated in methicillin-resistant strains of Staphylococcus epidermidis, S. haemolyticus, S. hominis, and S. simulans. In these four species, the apparent molecular mass of this protein was analogous to that of PBP 2' of methicillin-resistant S. aureus SR 1550-9. It exhibited a low affinity for methicillin, cephalothin, and cefamandole; and its synthesis was methicillin inducible. Peptide mapping of this PBP from the four species yielded identical results that were analogous to those obtained with S. aureus SR 1550-9. These results suggest that this protein is similar to, if not the same as, PBP 2' of S. aureus and that it is involved in methicillin resistance in the four species studied.
Bacterial Proteins↗
Novel extended-spectrum TEM-type beta-lactamase from an Escherichia coli isolate resistant to ceftazidime and susceptible to cephalothin.
A novel extended-spectrum TEM-type beta-lactamase was detected in an Escherichia coli isolate which was resistant to ceftazidime and susceptible to cephalothin. The corresponding bla gene was sequenced. The deduced amino acid sequence showed the following three amino acid replacements with respect to the TEM-2 sequence: Glu-->Lys-104, Arg-->Ser-164, and Glu-->Lys-240. Since it confers a ceftazidimase-type resistance phenotype, we propose for this novel enzyme the designation CAZ-9, corresponding to TEM-46 in the sequential numbering scheme of TEM beta-lactamases.
Ceftazidime↗
Double-blind comparison of phlebitis produced by cephalothin infusions with buffered and unbuffered diluents.
In a double-blind study with each patient as his own control, a buffered and an unbuffered cephalothin solution was administered to 13 patients in opposite arms for a period of 48 h each. Neither the incidence of phlebitis nor the degree of phlebitis was different with the two diluents, and there was no difference in the time of onset of phlebitis.
Buffers↗
Comparison of cefoxitin and cephalothin therapy of a mixed Bacteroides fragilis and Fusobacterius necrophorum infection in mice.
Cefoxitin, a beta-lactamase-resistant cephalosporin, was found to be more effective than cephalothin against an experimental mixed infection containing Bacteroides fragilis and Fusobacterium necrophorum.
Animals↗
Effect of cephalothin on renal cortical concentrations of gentamicin in rats.
Renal cortical concentrations of gentamicin were significantly lower in rats given this aminoglycoside and cephalothin simultaneously than in animals given gentamicin alone. This effect may be responsible, in part, for the reduction in nephrotoxicity reported previously in animals given the combination of drugs.
Animals↗
Antibacterial activity of cefuroxime, a new cephalosporin antibiotic, compared with that of cephaloridine, cephalothin, and cefamandole.
The in vitro activity of cefuroxime, a new cephalosporin derivative, was compared with that of cephaloridine, cephalothin, and cefamandole against strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. Cefuroxime showed very similar activity to cefamandole against Staphylococcus aureus, Haemophilus influenzae, and most members of the Enterobacteriaceae. It was more active than cefamandole against gonococci, pneumococci, and most streptococci. Increasing the inoculum size appeared to have less effect on the minimum inhibitory concentrations of cefuroxime for gram-negative bacilli than has been found with the other cephalosporin derivatives, and minimum bactericidal concentrations of cefuroxime were only marginally greater than minimum inhibitory concentrations.
Bacteria↗
Comparison of phlebitis produced by cephapirin and cephalothin.
In a single-blinded study involving 120 patients neither the incidence nor severity of phlebitis observed with cephapirin and cephalothin was significantly different.
Adult↗
Paper chromatographic techniques for the determination of cephalothin and desacetylcephalothin in body fluids.
Paper chromatographic procedures may be used to detect cephalothin and its metabolite desacetylcephalothin in urine, plasma, synovial fluid, and cerebrospinal fluid. Protein-bound antibiotics are released from plasma, cerebrospinal fluid, and synovial fluid by dilution with an equal volume of dimethylformamide. Data are presented on the sample preparation, paper chromatographic system, and other specific techniques.
Bacillus subtilis↗
Isolation of Serratia marcescens on deoxyribonuclease-toluidine blue-cephalothin agar.
Serratia marcescens was isolated on a new medium-commercial deoxyribonuclease agar with the addition of cephalothin (1,000 mug/ml) and Toluidine Blue (1,000 mug/ml). It was detected in water samples even though it comprised only 0.1 to 0.0001% of the total bacterial population.
Agar↗
Features of gentamicin nephrotoxicity and effect of concurrent cephalothin in the rat.
Sprague-Dawley rats given gentamicin from 10 to 70 mg/kg/day for 9 days showed a linear decrease in glomerular filtration rate with increasing dose, paralleled by histologic changes of acute tubular necrosis and cast formation only at the higher doses. Nephrotoxicity was correlated with the peak, rather than trough, serum gentamicin levels in this study, suggesting that it is the mean level of gentamicin over time that determines renal injury. The polyuria caused by gentamicin resulted mainly from a tubular concentrating defect rather than enhanced sodium or osmolal excretion and may be explained by the finding of a predominance of casts in the medullary thin limbs of the loops of Henle. No effect of gentamicin on the activity of cortical or medullary sodium-potassium adenosine triphosphatase was found to account for the modest sodium wasting. Concurrent administration of sodium cephalothin decreased the renal toxicity of gentamicin at high doses, an effect not explained by the added sodium or nonreabsorbable anion.
Acute Kidney Injury↗
Detection and characterization of polymers in cephalothin by passive cutaneous anaphylaxis in mice.
Immunization of BALB/c mice by repeated injections of cephalothin (CET) - Ascaris suum extract conjugate resulted in formation of IgE antibodies, which were able to sensitize syngeneic animals for passive cutaneous anaphylaxis (PCA). By means of high-pressure liquid chromatography, a fraction with extremely high PCA-eliciting activity, but without appreciable antimicrobial activity, was isolated from the CET preparation. Physicochemical analyses of the fraction identified the major component of polymer impurities as being a proteinaceous complex with a molecular weight of 6,580. Very little cross-reactivity of CET and potassium benzyl penicillin (PcG) was noted when these antibiotics were used as the challenge antigens for PCA induced by corresponding murine antisera. The results of the inhibition studies indicated, however, that at least two antigens were involved in the PCA induced by anti-CET antibodies, one strictly specific for CET and another shared by PcG. Evidence was also presented that the nucleus structure and acyl side-chain structure of CET play the major role in the PCA elicited by the challenge with CET and its polymer, respectively.
Animals↗
Comparison of in vitro activities of eight new beta-lactam compounds against cephalothin-resistant Enterobacteriaceae from hospital patients.
The in vitro antibacterial activity of eight newer beta-lactam antibiotics (mecillinam, piperacillin, mezlocillin, cefoxitin, cefotaxime, moxalactam, ceftriaxone and ceftazidime) was determined against 87 cephalothin-resistant strains of Enterobacteriaceae isolated during 6 months in a general hospital. Ceftriaxone, cefotaxime, moxalactam and ceftazidime proved to be highly active; only a minority of strains required higher concentrations than 0.125 microgram/ml for inhibition of growth. Cefoxitin, mecillinam, mezlocillin and piperacillin were less active. Mecillinam displayed greater efficacy against Escherichia coli, Klebsiella and Enterobacter spp., while the same was the case for piperacillin against Proteus mirabilis and Serratia marcescens, and for cefoxitin against indole-positive Proteus spp. The production of beta-lactamase was correlated with a reduced activity of mecillinam, mezlocillin and piperacillin but not of cefoxitin or the other beta-lactamase-stable cephalosporins. However, some strains, mainly those of Proteus, Enterobacter and Serratia, though resistant to mecillinam, mezlocillin and piperacillin did not produce beta-lactamases. This observation might indicate that ceftriaxone, moxalactam, cefotaxime and ceftazidime, besides their indifference to beta-lactamases, are characterized also by a high degree of intrinsic activity.
Anti-Bacterial Agents↗
Comparative biliary concentrations of cephazolin and cephalothin in patients with biliary tract disease.
The concentration of cephazolin in the serum, gall bladder bile, common duct bile, and gall bladder wall were consideredably higher than cephalothin especially with IV administration and indicate that cephazolin should be a useful antibiotic in the surgical treatment of acute cholecystitis.
Adult↗