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PubMed1981

Capsules, infection, and intraluminal antibiotics.

Staphylococcus epidermidis, a normal cutaneous inhabitant previously shown to be present in 67 percent of nipple secretions, has been cultured from 55 percent of surgical mammary pockets prior to implant insertion and from the interior of 71 percent of fibrous capsules explored at open capsulotomy. Cephalothin and gentamicin placed within the lumen of inflatable breast implants in vitro have been shown to diffuse outward through the silicone shell. The use of intraluminal cephalothin and gentamicin in vivo has significantly reduced our incidence of capsular contracture following both primary mammary augmentation and secondary open capsulotomy. The authors believe that the cause of fibrous capsular contracture may be a low-grade periprosthetic infection, and that the unique permeability characteristics of the silicone shell may permit sustained antimicrobial activity at the surface of the prosthesis.

Cephalothin↗
PubMed1977

Open-heart surgery.

A randomized prospective study of the relative effectiveness of broad-spectrum versus specific antistaphylococcal antibiotic prophylaxis in open-heart surgery was done between May 1972 and June 1973. All patients undergoing open-heart surgery were assigned randomly (by hospital number) to receive either methicillin (M) or cephalothin (C) beginning the night before operation. There were 132 patients in the C group and 129 in the M group. There were no statistically significant differences in age or duration of hospitalization, cardiopulmonary bypass, urinary tract drainage, or postoperative fever. There was a significant difference in the ratio of male to total patients (0.67 C, 0.52 M, P less than .02) and duration of operation in hours (4.27 C, 3.87 M, P less than .02). A statistically significant higher rate of urinary tract infection (3 C, 22 M, P less than .05), pneumonia (0 C, 9 M, P less than .01), and episodes of sepsis and prosthetic endo carditis (0 C, 11 M, P less than .001) was found in the methicillin group. The incidence of wound infections and positive cultures from blood obtained immediately after termination of cardiopulmonary bypass was not significantly different. Cephalothin replaced methicillin as the routine antibiotic prophylaxis for open-heart surgery at our institution.

Adult↗
PubMed1978

Methicillin-resistant Staphylococcus epidermidis.

Staphylococcus epidermidis is frequently associated with infection of prosthetic heart valves, prosthetic orthopedic devices, and neurosurgical shunts. Penicillinase-resistant semisynthetic penicillins, such as methicillin, have been the therapeutic and prophylactic agents of choice for S epidermidis infection. However, more S epidermidis isolates are now resistant to methicillin and other penicillins. In our laboratory 41% of S epidermidis isolates were resistant to methici-lin. All of the methicillin-susceptible isolates and 82% of the methicillin-resistant isoates were susceptible to cephalothin. Cephalothin should replace methicillin as the prophylactic and therapeutic agent of choice in institutions with a high percentage of methicillin-resistant S epidermidis.

Cephalothin↗
PubMed1987

Antibiotic penetration into rabbit nucleus pulposus.

A rabbit model was used to determine the penetration of four commonly used antibiotics (clindamycin, tobramycin, cephalothin, and oxacillin) into the nucleus pulposus after receiving an 8-hour course of intramuscular antibiotic injections. Clindamycin and tobramycin achieved therapeutic levels in the nucleus pulposus and both were present in greater than 50% of serum levels. Cephalothin was not detected in the nucleus pulposus and penetrated at less than 4% of serum levels at 1 hour after injection. The data were inconclusive regarding oxacillin penetration.

Animals↗
PubMed1983

Studies on the mechanism of intrinsic resistance to beta-lactam antibiotics in group D streptococci.

Six penicillin-binding proteins (PBPs) were detected in clinical isolates of each one of three group D streptococci: Streptococcus bovis, S. faecalis and S. faecium. When examined in whole organisms, the PBPs of S. faecium, the most penicillin-resistant species of group D streptococci, generally had lower affinities for the antibiotic than those of S. faecalis (intermediate penicillin resistance), which in turn were of lower affinity than those of S. bovis (penicillin-sensitive). On the other hand, no quantitative correlation could be established between the binding of penicillin to any one PBP or group of PBPs, and the penicillin MIC value for the corresponding micro-organism. Examination of the amounts of antibiotic bound and the rates of binding to PBPs of equal numbers of protoplasts and whole bacteria of S. faecalis and S. faecium, indicated that there was no permeability barrier to benzylpenicillin in the cell walls of these species. The lower antibacterial effectiveness of cephalothin compared with ampicillin in group D streptococci was paralleled by the higher concentrations of cephalothin needed in competition assays to inhibit the lower molecular size PBPs of these bacteria.

Ampicillin↗
PubMed1975

Positive direct antiglobulin (Coombs') test caused by cephalexin administration in humans.

Of 71 patients showing a negative direct antiglobulin (Coombs') test (DAT) before administration of cephalexin (CEX) three developed a positive DAT after therapy with this drug (4 percent). No case of immunohemolytic anemia was observed. The sera of the patients with a positive DAT reacted with cephalothin-coated red cells producing high titers, with penicillin cells normal titers and with CEX cells low titers. Since the red cell eluates of these patients did not give significant reactions with red cells sensitized with CEX, cephalothin and penicillin, a nonimmunological mechanism for the development of the positive DAT in these patients has to be assumed.

Adolescent↗
PubMed1980

Effects of some antibacterial agents on the phagocytosis of 32P-labelled Escherichia coli by human polymorphonuclear cells.

Gentamicin, trimethroprim, cephalothin, colistin, erythromycin, oxytetracycline and chloramphenicol were studied in a phagocytic system. A radiolabelled strain of E. coli was used as test bacterium and human polymorphonuclear cells were used as phagocytes. Except for trimethoprim and cephalothin, there was a tendency towards depression of the process of phagocytosis in the presence of high concentrations of the various antibiotics. Colistin in a high concentration (83 micrograms/ml) exerted the most significant effect.

Anti-Bacterial Agents↗
PubMed1985

Comparative in vitro activity of four beta-lactam antibiotics in surgical wound fluid against staphylococci.

Minimal inhibitory and bactericidal concentrations (MIC and MBC) of methicillin, dicloxacillin, cephalothin and cefuroxime were determined against 26 strains of staphylococci, using a broth dilution method with surgical wound fluid (WF) and Mueller-Hinton broth (MH) as test media. The staphylococci were all clinical isolates; 17 strains were coagulase-positive and 9 were coagulase-negative. The MIC-values of dicloxacillin and cephalothin estimated in MH were lower than those estimated in WF. For methicillin and cefuroxime the MIC-values in the two media were similar. With regard to MIC-values, the two penicillins were identical in WF, as were the two cephalosporins, but the cephalosporins were found to be more active than the penicillins, with an average of one dilution step. As regards the MBC to MIC ratios, no differences were found neither between the two media nor between the four antibiotics.

Anti-Bacterial Agents↗
PubMed1980

Inhibitors of alpha-chymotrypsin derived from cephalosporins: structure-activity relationships.

Cephalothin and certain other cephalosporins are irreversible inhibitors of alpha-chymotrypsin in near neutral media. The active inhibiting species is slowly generated in small yield from cephalothin in aqueous solution. Structure-activity studies for 37 other cephalosporins and related compounds establish that inhibitors of the enzyme require in the parent cephalosporin molecule a 7-acyl substituent containing a flat area in the form of an aromatic or heterocyclic ring together with a 3-acetoxymethyl or other substituent which is labile to water. The inhibitory species is considered to be the oxazolinone derived from the corresponding cephalosporoic acid.

Cephalosporins↗
PubMed1976

Comparison of thrombophlebitis associated with three cephalosporin antibiotics.

A double-blind study with volunteers was performed to determine the incidence and severity of thrombophlebitis associated with cephalothin, cephapirin, cefamandole, and a water control. Although there were no statistical differences in the incidence of thrombophlebitis, cephalothin resulted in significantly more severe thrombophlebitis compared with the other agents.

Cephalosporins↗
PubMed1977

Inhibition of amino acid transport in Escherichia coli by some beta-lactam antibiotics.

Among 10 antibiotics tested, cephaloridine and cephalothin showed the greatest inhibition of proline active transport. Ethylenediaminetetraacetate pretreatment of the cells did not enhance inhibition by any of these 10 antibiotics. The inhibition of active transport of 10 additional amino acids by cephaloridine and cephalothin was studied. Both antibiotics inhibited transport of three amino acids which, like proline, have transport systems resistant to osmotic shock; neither antibiotic inhibited transport of the remaining amino acids, including three with shock-resistant and four with shock-sensitive systems.

Amino Acids↗
PubMed1977

In vitro activity of cefaclor, a new orally administered cephalosporin antibiotic.

The in vitro antibacterial activity of cefaclor, cephalothin, and cephalexin against 261 clinical isolates of Staphylococcus aureus and Enterobacteriaceae was compared. Cefaclor and cephalexin were about equally active against S. aureus. Cefaclor was the most active cephalosporin against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. The effect on the antimicrobial activity using a relatively high and low inoculum was pronounced for cefaclor when compared with that of cephalothin.

Bacteria↗
PubMed1978

Incidence and characteristics of antibiotic-tolerant strains of Staphylococcus aureus.

Thirty clinical isolates of Staphylococcus aureus were tested for tolerance to oxacillin, cephalothin, and gentamicin by using killing curves and broth dilution susceptibility tests. Tolerance was defined as the presence of>/=100 colony-forming units per ml remaining after 24 h of incubation of the killing curve suspensions. Nineteen of 30 isolates were tolerant to oxacillin and cephalothin, but none was tolerant to gentamicin. Among the tolerant isolates, there was a wide spectrum of tolerance, with from 0.2 to 43% of the colony-forming units in the starting inoculum remaining after 18 to 24 h of incubation. Tolerance was unrelated to phage type or to any of several other characteristics studied.

Anti-Bacterial Agents↗
PubMed1978

Comparison of serum bactericidal activity among three antimicrobial combinations.

Three antimicrobial combinations, ticarcillin plus cephalothin (T+C), ticarcillin plus gentamicin (T+G), and cephalothin plus gentamicin (C+G), were administered to 105 febrile granulocytopenic cancer patients at the Baltimore Cancer Research Center as part of a multi-institutional prospective randomized antibiotic trial. The sera from 32 of these patients (T+C-10 patients, T+G-10 patients, and C+G-12 patients) obtained 1 h post-antibiotic administration were examined for bactericidal activity against 11 strains each of the most common pathogens infecting the granulocytopenic host: Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Each of the three antibiotic regimens produced a high degree of bactericidal activity in these sera against S. aureus and E. coli. P. aeruginosa was equally, although poorly, killed by sera containing ticarcillin (T+G, T+C), whereas C+G produced no measurable serocidal activity (P < 0.05). Sera with C+G killed K. pneumoniae more effectively than T+G; T+C produced the least killing effect of the three regimens against this organism (P < 0.05). The bactericidal activity of the serum from these 32 patients supplements the overall clinical results of the multi-institutional antibiotic trial and suggests that T+G is a useful initial regimen for empiric therapy of febrile episodes in granulocytopenic cancer patients.

Anti-Bacterial Agents↗
PubMed1980

Bioassay of antibiotics in body fluids from patients receiving cancer chemotherapeutic agents.

Patients receiving antitumor chemotherapy are at increased risk of developing nosocomial infections, and the antibacterial therapy of such infections is often monitored by bioassay. The effect of antitumor agents on seven bioassay procedures using strains of Sarcina, Klebsiella, Clostridium, Pseudomonas, Staphylococcus aureus, and S. epidermidis or Bacillus was evaluated. The minimum inhibitory concentrations of six antitumor drugs, cytarabine, dactinomycin, doxorubicin, 5-fluorouracil, methotrexate, and vinblastine, determined for each of the test organisms, showed that 5-fluorouracil, dactinomycin, and doxorubicin are used at blood levels sufficient to interfere with bioassay procedures. The other drugs have minimum inhibitory concentrations as much as 100 times the expected blood levels. Antibiotic (gentamicin, kanamycin, cephalothin, and carbenicillin) recovery experiments in the presence of therapeutic levels of antitumor agents showed no in vitro inactivation of antibiotic. However, at low cephalothin concentrations (less than 20 microgram/ml) in the presnce of 5-fluorouracil, bioassay results were in error by as much as 100%. The data indicate that bioassay procedures for the determining of antibacterial drug levels may need to be modified for those patients receiving antitumor therapy with 5-fluorouracil, doxorubicin, or dactinomycin.

Anti-Bacterial Agents↗
PubMed1982

Bactericidal activity of antibiotics against Legionella micdadei (Pittsburgh pneumonia agent).

The bactericidal activity of five antibiotics for Legionella micdadei was determined by the construction of time-kill curves. Erythromycin, rifampin, penicillin G, cephalothin, and gentamicin were bactericidal for L. micdadei at readily achievable concentrations. The minimal bactericidal concentrations, defined as those producing 99.9% killing within 24 h, were: erythromycin, 4.6; rifampin, 0.13; penicillin G, 0.25; cephalothin, 2.5; and gentamicin, 0.25 micrograms/ml. The ratios of the minimal bactericidal to minimal inhibitory concentrations for these antibiotics ranged from 1 to 8. Thus, the poor in vivo activity of beta-lactam and aminoglycoside antibiotics against L. micdadei cannot be ascribed to a lack of killing by these agents.

Anti-Bacterial Agents↗
PubMed1986

Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin.

Serum bactericidal activities (SBAs) were studied after intravenous administration of pefloxacin (8 mg/kg) and amikacin (7.5 mg/kg) alone or in combination to 15 human volunteers. About 10 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested. The serum levels of pefloxacin were measured microbiologically by using E. coli KP 1976-712 as the test organism at 0, 30, 60, 120, and 720 min after infusion; at 0, 30, 60, and 720 min these levels were 7 +/- 1.4, 5 +/- 0.8, 4.5 +/- 0.7, and 2.1 +/- 0.6 mg/liter (mean +/- standard deviation), respectively, with a terminal half-life of 10 h. The serum levels of pefloxacin in the presence of amikacin were measured similarly; 1% sodium polyanethol sulfonate was added to the agar to inactivate amikacin. Treatment with pefloxacin alone resulted in high SBAs against E. coli, K. pneumoniae strains susceptible to cephalothin, and Staphylococcus aureus at the peak concentration; 81 to 100% of the sera had SBAs of greater than or equal to 1:8. However, treatment with pefloxacin alone resulted in low SBAs against K. pneumoniae strains resistant to cephalothin and P. aeruginosa; only 34% of the sera had SBAs of greater than or equal to 1:8. At trough concentrations the percentages of sera with SBAs greater than or equal to 1:8 were 75 to 83% (E. coli), 9 to 27% (K. pneumoniae), 0% (P. aeruginosa), and 10% (S. aureus). The combination of pefloxacin plus amikacin was most often additive; the peak activity was due to amikacin, and the trough activity was due to pefloxacin. Occasionally antagonism occurred with P. aeruginosa, K. pneumoniae, and S. aureus strains. These observations were confirmed by the killing curves in pooled serum obtained at peak and trough levels. Regrowth was observed for seven strains of P. aeruginosa treated with pefloxacin alone; amikacin seemed to prevent this phenomenon.

Amikacin↗
PubMed1973

Clinical and in vitro evaluation of cefazolin, a new cephalosporin antibiotic.

Cefazolin sodium, a cephalosporin for parenteral use, was evaluated in vitro and in 26 patients. Cefazolin had activity equivalent to cephalothin against Streptococcus pneumoniae, Staphylococcus aureus, group A streptococci, and Proteus mirabilis. Cefazolin was four- to eightfold more active against Escherichia coli and slightly more active against Klebsiella pneumoniae, whereas cephalothin was slightly more active against indole-positive Proteus species. After a 500-mg dose of cefazolin intramuscularly, peak concentrations in the serum were high enough to inhibit all strains of S. pneumoniae, S. aureus, group A streptococci, E. coli, K. pneumoniae, and P. mirabilis, as well as 60% of strains of Proteus species other than P. mirabilis. All of 26 patients (18 with pneumonia, 6 with urinary tract infection, and 2 with skin infections) responded clinically and bacteriologically to cefazolin therapy. There were no major side effects of therapy, and no patient complained of pain at the site of intramuscular injection. Cefazolin is an effective cephalosporin which can be used intramuscularly for therapy of serious bacterial infections. Its major advantages over other cephalosporins are higher, more sustained concentrations in the blood and apparent lack of pain on intramuscular injection.

Adult↗