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PubMed1978

Pharmacokinetics of cephalosporins in patients with normal or reduced renal function.

The pharmacokinetic distribution of 10 cephalosporin compounds, cephalothin, cephaloridine, cephaloglycine, cephalexin, cefazolin, cephapirin, cephradine, cephacentrile, cefoxitin, and cefamandole, in patients with various degrees of renal function was reviewed. The mean serum half-life (t1/2) of each cephalosporin compound was calculated from reported data in patients grouped according to their degree of renal function, as determined by the rate of creatinine clearance. Mean t1/2 values in patients with normal renal function were compared with t1/2 values for the same cephalosporin in patients with moderate renal failure and severe renal azotemia. The effect of hemodialysis and peritoneal dialysis on the mean serum t1/2 of each cephalosporin was also determined. The mean serum t1/2 of each cephalosporin progressively increased as the rate of creatinine clearance decreased. Hemodialysis decreases the t1/2 of cephaloridine, cephalexin, cefazolin, and cephacetrile but only minimally influences the t1/2 of cephalothin and cefamandole. Peritoneal dialysis reduces the t1/2 of cephalothin and cephaloridine but only minimally influences the t1/2 of cefazolin and cefamandole.

Cephalexin↗
PubMed1999

Molecular typing of multiresistant Klebsiella pneumoniae isolated from children from northern Jordan.

Twenty-nine clinical isolates of community acquired Klebsiella pneumoniae obtained from 17 children with malnutrition were characterized by antibiotic susceptibility, plasmid analysis, and random amplified polymorphic DNA (RAPD) techniques. Disc diffusion methodology was used to test the susceptibility of the isolates to 13 antibiotics: amoxycillin, cephapirin, ceftazidime, cefoxitin, cefotaxime, aztreonam, gentamicin, ciprofloxacin, chloramphenicol, erythromycin, nalidixic acid, trimethoprim and amoxycillin-clavulanic acid. All the isolates showed multiresistance patterns (15 patterns) ranging from resistance to two antibiotics to resistance to 10 antibiotics. All isolates were resistant to amoxycillin and erythromycin. Ten K. pneumoniae isolates producing extended-spectrum beta-lactamases (ESBLs) as evidenced by the double-disc diffusion synergy test were isolated sporadically from six patients. Six of these 10 isolates were hyperproducers of ESBL, which resulted in increased resistance to the beta-lactam-beta-lactamase inhibitor combination amoxycillin-clavulanic acid. Plasmid analysis showed plasmid ranging in size from 48 kilobases (kb) to 1.4 kb. All the 29 isolates shared the same plasmid 26 kb. There was a consistent relationship between antibiotype and plasmid profiles for each pair of isolates obtained from five individual patients. RAPD analysis using a single (10-mer) primer demonstrated that the isolates that have the same antibiotype and the same plasmid profile had different RAPD fingerprint patterns. These results demonstrate that the RAPD technique is better than antibiotype characterization and a plasmid analysis profile for typing K. pneumoniae as well as for revealing strain differences.

Anti-Bacterial Agents↗
PubMed1978

Antibiotic concentration in human wound fluid after intravenous administration.

Since the wound is the most common focus of infection in the surgical patient, adequate levels of antibiotic within the wound ar essential. This study examines the concentrations of antibiotic achieved in human wounds. Fluid was collected at timed intervals on the first postoperative day from the wounds of 56 patients receiving antibiotics after regional lymph node dissection. Antibiotic concentration was determined by bioassay. Six antibiotics were studied: cephalothin, cefazolin, cephapirin, oxacillin, ampicillin and clindamycin. The cephalosporins and penicillins showed similar patterns of appearance in the wound fluid. The peak level occurred early (1--1 1/2 hours) with subsequent slow decrease. Clindamycin produced nearly constant levels in wound fluid. The concentration of each antibiotic in wound fluid surpassed the serum levels after 2.5 hours. At the dosages studied each antibiotic produced wound fluid concentrations greater than the MIC for most susceptible organisms. Higher doses provided higher wound fluid levels. The rate of appearance and the levels achieved should be considered in the choice of antibiotics in the surgical subject.

Anti-Bacterial Agents↗
PubMed1995

Prophylactic antibiotic use in pediatric cardiovascular surgery: a survey of current practice.

There is little information on prophylactic antibiotic practice in pediatric cardiovascular surgery. A consensus prophylactic antibiotic practice, if identified, might serve as a standard to which alternative prophylactic antibiotic practice could be compared. We surveyed North American academic centers with pediatric cardiovascular surgery programs regarding their standard antimicrobial prophylaxis regimens, duration of prophylaxis and modification of prophylaxis for lesion, patient age or medical device considerations. Forty-three (81%) of 53 centers responded; not all responses were complete. Monotherapy was used by 39 (91%) of 43; 38 (97%) of 39 used a 1st or 2nd generation cephalosporin (cefazolin 24, cefamandole 8, cefuroxime 4, cephapirin 1, unspecified 1) and 1 of 39 used vancomycin. Only 4 (9%) of 43 used 2 antibiotics. Prophylactic antibiotics were started pre- or intraoperatively by 41 of 43 centers and discontinued within 2 days by 25 of 37. Prophylactic antibiotics were often continued while thoracostomy tubes (29 of 43), mediastinal tubes (31 of 43) or transthoracic vascular catheters (22 of 43) were in place, but usually not for endotracheal tubes (6 of 43), arterial (9 of 43) or percutaneous central venous (13 of 43) catheters or temporary pacing wires (6 of 43). Our survey indicates that the consensus prophylactic antibiotic regimen for pediatric cardiovascular surgery is monotherapy with a first or second generation cephalosporin, used for < or = 2 days or until transthoracic medical devices are removed.

Anti-Bacterial Agents↗
PubMed1993

The postantibiotic effect of selected antibiotics on Staphylococcus aureus Newbould 305 from bovine intramammary infection.

The postantibiotic effect (PAE) was determined for selected antibiotics against Staphylococcus aureus Newbould 305 originating in vivo from mastitic milk and compared with the PAE for the same S. aureus strain cultured in vitro. The PAE was measured at 2 and 4 times the MIC for 1 and 2 h of exposure. The PAE of penicillin, pirlimycin, and tilmicosin were reduced against S. aureus 305 originating in vivo compared with S. aureus 305 grown in vitro. The PAE of cephapirin was increased against S. aureus originating in vivo. Minimal effect on PAE was noted for novobiocin. The PAE for rifampicin extended beyond the limits of the test parameters (> 180 min) for all antibiotic concentrations, media, and exposure times tested, except at 2 times the MIC and at 1 h exposure when the PAE was reduced to 60 min for S. aureus 305 originating in vivo. The PAE of an antibiotic may be an important consideration in determining therapy intervals and antibiotic concentrations for treatment of bovine mastitis.

Animals↗
PubMed1995

In vitro efficacy of cefquinome (INN) and other anti-infective drugs against bovine bacterial isolates from Belgium, France, Germany, The Netherlands, and the United Kingdom.

The in vitro antibacterial activity of cefquinome (INN), an aminothiazolyl-cephalosporin of the fourth generation of cephalosporins, was investigated by determining the minimal inhibitory concentration (MIC, microgram/ml) for 714 bacterial isolates of bovine origin and comparing it with those of amoxicillin, amoxicillin and clavulanic acid, ceftiofur, cephapirin, enrofloxacin, gentamicin, kanamycin and oxytetracycline. Drug resistance was determined by using break-points, which consider the dosage regimen and pharmacokinetics of the veterinary antimicrobials investigated. Cefquinome demonstrated a very high in vitro activity against bacterial isolates of Pasteurella spp., Escherichia coli and Salmonella spp. Overall, the level of resistance against the different anti-infectives tested was lowest for cefquinome. For the remaining substances examined, in vitro activity and the level of resistance showed considerable differences. The chemical and pharmaceutical features of cefquinome are discussed.

Animals↗
PubMed1983

Epileptogenic activity of cephalosporins in rats and their structure-activity relationship.

The epileptogenic properties of 10 cephalosporins and penicillin G were compared by intraventricular application to rats. At doses greater than 32 micrograms per head, cefazolin provoked tremendous seizure signs, a spike-and-wave complex appeared in close succession for more than 30 min, and severe convulsions were observed repeatedly. Reactions to cefotiam, ceftezole, and cephaloridine were almost equal to reactions to penicillin. No epileptogenic signs were observed on EEGs, and no behavioral symptoms were observed after administration of 1,000 micrograms of cephalexin and cephradine per head. Reactions to cephapirin, cefmetazole, cephalothin, and ceftizoxime exhibited less marked epileptogenic features; activity was diminished in that order on EEGs and in behavioral signs. Compounds substituted with two different heterocyclic rings at position 7 (R1) and position 3 (R2) of 7-aminocephalosporanic acid were potent in producing epileptogenic signs both on EEGs and in behaviors. Compounds substituted with a heterocyclic ring at either position of 7-aminocephalosporanic acid were less potent. Compounds such as ceftizoxime, cephalexin, and cephradine, substituted at R2 with small groups, were almost incapable of producing epileptogenic activity. This may indicate that the substitution of a heterocyclic ring at position 3 will provoke the convulsive actions.

Animals↗
PubMed1976

Comparison of the in vitro activity of several cephalosporin antibiotics against gram-negative and gram-positive bacteria resistant to cephaloridine.

The in vitro activity of each of two oral [cefatrizine (BL-S640), cephalexin] and three parenteral (cefamandole, cefazolin, cephapirin) cephalosporin antibiotics was compared with that of cephalothin against 168 clinical isolates of gram-negative and gram-positive bacteria selected as resistant to 20 mug of cephaloridine per ml on the basis of agar dilution susceptibility test data. Each of the five other cephalosporins inhibited a greater percentage of gram-negative bacillary isolates than did cephalothin or cephaloridine, with minimal inhibitory concentration values ranging 2- to 50-fold lower. Significant differences between minimal inhibitory concentrations of the compounds tested were also observed in tests against strains of Streptococcus faecalis and of methicillin-resistant Staphylococcus aureus. Potential advantages of including more than a single cephalosporin antibiotic in the panel of antibiotics used for routine susceptibility testing, suggested by these observations, are discussed.

Bacteria↗
PubMed1976

Cephalosporin and aminoglycoside concentrations in peritoneal capsular fluid in rabbits.

To study the penetration of antibiotics into peritoneal tissue fluid, a subcutaneous tissue capsule model was modified by implanting multiple, perforated spherical capsules in the peritoneal cavity of rabbits. Capsules became vascularized, encased in connective tissue, and filled with fluid having a mean protein concentration of 3.6 g/100 ml. Capsular fluid was obtained by percutaneous needle aspiration and assayed for antibiotic by the disk plate bioassay technique. Cephalosporins were administered intramuscularly at a dose of 30 mg/kg. Mean peak concentrations of cephaloridine and cefazolin were significantly higher than cephalothin and cephapirin in capsular fluids, but the percent penetration (ratio of capsular mean peak to serum mean peak) ranged from 8.7 to 16.9% and was not significantly different among the cephalosporins. At 24 h the capsular concentration of cefazolin was significantly greater than for the other cephalosporins (P < 0.001). Lower rabbit serum protein binding observed at high in vivo concentrations may have enabled cefazolin to penetrate capsular fluid, but in vitro protein binding studies did not confirm a decrease in serum protein binding at high concentrations within the clinical range. Kanamycin and amikacin showed comparable capsular fluid peak concentrations as did gentamicin and tobramycin. The percent penetration ranged from 15.2 to 34.5% for the aminoglycosides. The only statistical difference was that amikacin penetration was significantly higher than that for tobramycin. Mean capsular concentrations of amikacin, cefazolin, and cephaloridine compared most favorably with the minimum inhibitory concentration of gram-negative bacilli at the dosages used in this study.

Aminoglycosides↗
PubMed1978

Use of a heavy inoculum in the in vitro evaluation of the anti-staphylococcal activity of 19 cephalosporins.

The in vitro activity of 19 cephalosporins against 105 clinical isolates of Staphylococcus aureus and S. epidermidis was determined by using a heavy inoculum, i.e., 10(8) to 10(9) organisms per ml, to maximally challenge the antibiotics. The anti-staphylococcal activities of cephaloridine and 87/312 were consistently decreased by the use of a heavy inoculum when compared with the activity obtained with two less-concentrated inocula. The activity of most of the other compounds was also decreased with the use of a heavy inoculum, but this was observed only with selected isolates. Cephapirin, cephalothin, and cefazaflur were the most active drugs against the methicillin-susceptible isolates. Cephaloridine, cefamandole, cefazaflur, and 87/312 had substantial activity against methicillin-resistant staphylococci even with heavy inocula. With the exception of cefaclor against S. aureus, the orally absorbed cephalosporins were generally one-half to one-sixteenth as active as the parenterally administered cephalosporins. The median minimal inhibitory concentrations of five of the 12 parenteral cephalosporins were lower with the methicillin-susceptible S. aureus than with the methicillin-susceptible S. epidermidis strains.

Bacteriological Techniques↗
PubMed1978

Susceptibility of Eikenella corrodens to ten cephalosporins.

The susceptibility of 24 strains of Eikenella corrodens was determined, by the agar dilution technique, to 10 cephalosporins, as well as to clindamycin, penicillin and dicloxacillin. All strains were uniformly very susceptible to penicillin G and cefoxitin and resistant to clindamycin and dicloxacillin. Cefazolin showed good activity. Cephalexin, cephradine, and cefadroxil showed poor activity, and cefamandole's activity was relatively poor. Cephalothin, cephapirin, cefaclor, and cephaloridine showed moderate activity, with some strains relatively resistant.

Bacteroides↗
PubMed1979

Clinical and laboratory evaluation of cefamandole in the therapy of Haemophilus spp. Bronchopulmonary infections.

A prospective, randomized, single-blind comparison of parenteral cefamandole and ampicillin was conducted in 27 hospitalized adult patients with pneumonia or purulent tracheobronchitis due to Haemophilus spp. Patients received either parenteral cefamandole or ampicillin in a dose of 1 g every 6 h. Cefamandole was as effective and safe as ampicillin. Of the 14 patients treated with cefamandole, 13 were considered cured, as were 12 of the 13 treated with ampicillin. One patient in each treatment group improved clinically but did not clear his sputum of Haemophilus spp. One patient treated with cefamandole had a recurrence of Haemophilus spp. bronchitis 9 days after cure. Adverse effects were more common in the cefamandole-treated group (50% versus 15%), but were mild and did not require discontinuation of therapy in any patient. The in vitro susceptibilities of 64 clinical isolates of Haemophilus spp. to 10 antibiotics were determined. Cefamandole was the most active of the cephalosporin-cephamycin antibiotics tested, inhibiting 98% of 61 non-beta-lactamase-producing isolates at 2 mug/ml and 100% at 4 mug/ml. Cefamandole inhibited the three ampicillin-resistant isolates at 2 mug/ml or less. Cephapirin, cefoxitin, and cephalothin were the next most active, whereas cefazolin and cephradine were the least active.

Adult↗
PubMed1979

Comparative susceptibility of Haemophilus species to cefaclor, cefamandole, and five other cephalosporins and ampicillin, chloramphenicol, and tetracycline.

The minimal inhibitory concentration of cefaclor, cephalexin, cephradine, cefamandole, cephalothin, cephapirin, cefazolin, ampicillin, chloramphenicol, and tetracycline for inhibition of 198 freshly isolated clinical strains of Haemophilus species (23 H. influenzae type b, 157 H. influenzae non-type b, 14 H. parainfluenzae, and 4 H. aphrophilus) was determined simultaneously by a slightly modified WHO-ICS agar dilution method. Nine strains were resistant to ampicillin. There was no correlation between ampicillin resistance and minimal inhibitory concentration of other antibiotics. All strains were susceptible to chloramphenicol, and all except five were susceptible to tetracycline. Cefaclor was the most active oral cephalosporin, and cefamandole was the most active parenteral cephalosporin. Among the seven cephalosporins tested, cefamandole was the most effective compound. All but two strains were inhibited by cefamandole at 2 mug or less per ml.

Ampicillin↗
PubMed1980

Antibiotic susceptibility of beta-lactamase-producing strains of Branhamella (Neisseria) catarrhalis.

All 11 clinically significant isolates of Branhamella catarrhalis examined in this study were found to produce beta-lactamase. The enzyme was apparently not plasmid associated since extrachromosomal deoxyribonucleic acid was not detected in any of the strains. The beta-lactamase activity of all strains was significantly depressed by the beta-lactamase inhibitors clavulanic acid and CP 45899. Based on comparisons of relative susceptibility to various beta-lactam antibiotics, it was inferred that the beta-lactamase of B. catarrhalis was significantly more active against penicillin congeners than against cephalosporin congeners. Most strains were not inhibited by readily achievable serum concentrations of the pencillinase-sensitive penicillins, penicillin G, ampicillin, and amoxicillin. Methicillin was equally ineffective. With rare exceptions, most strains of B. catarrhalis were inhibited by achievable serum concentrations of seven cephalosporins (cephalothin, cephapirin, cephaloridine, cephalexin, cephamandole, cefaclor, and cefuroxin) and one cephamycin (cefoxitin). All strains were uniformly resistant to clindamycin but were inhibited by achievable serum concentrations of erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. Comparison of geometric mean minimum inhibitory concentrations of all antimicrobial agents tested suggested that B. catarrhalis was most susceptible to cefoxitin, erythromycin, and tetracycline.

Anti-Bacterial Agents↗
PubMed1982

Stability of antimicrobial agents in peritoneal dialysate.

The stability of cephapirin, gentamicin, penicillin G, nafcillin, ticarcillin, and vancomycin was tested in peritoneal dialysate at 25 degrees C for 24 h. All of the antimicrobial agents were stable except penicillin G, which lost 25% of activity over 24 h (P less than 0.01). The once-daily preparation of drug-dialysate solution is feasible for the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis.

Anti-Bacterial Agents↗
PubMed1984

High-pressure liquid chromatographic method for analysis of cephalosporins.

A high-pressure liquid chromatographic method is described for the analysis of a wide range of cephalosporin congeners, using only three reagents for extraction and drug analysis. Plasma was treated with cold methanol-0.1 M sodium acetate to precipitate protein. Cephalosporins were resolved on a C-18 reverse-phase column, utilizing a mobile phase of various percentages of 0.01 M sodium acetate and acetonitrile-methanol. Compounds analyzed included cephalexin, cefamandole, cephalothin, cefotaxime, cefazolin, cephaloridine, cefoxitin, cefaclor, cephapirin, and cefoperazone. Each antibiotic demonstrated excellent linearity throughout the therapeutic range. The method of standard additions revealed recoveries of 93 to 101%, with detection limits ranging from 0.2 to 1.0 micrograms/ml for these drugs. Retention times ranged from 4 to 6 min. This method offers a rapid and simple means by which this group of cephalosporins may be reliably quantitated.

Cephalosporins↗
PubMed1985

Determination of in vitro susceptibility of Mycobacterium tuberculosis to cephalosporins by radiometric and conventional methods.

Among eight cephalosporins and cephamycins tested in preliminary in vitro screening against Mycobacterium tuberculosis, the most promising for further study was found to be ceforanide, followed by ceftizoxime, cephapirin, and cefotaxime. Moxalactam, cefoxitin, cefamandole, and cephalothin were found to be not active enough against M. tuberculosis to be considered for further in vitro studies. The antibacterial activity of various ceforanide concentrations was investigated by three methods: (i) the dynamics of radiometric readings (growth index) in 7H12 broth; (ii) the number of CFU in the same medium; and (iii) the proportion method on 7H11 agar plates. There was a good correlation among the results obtained with these methods. The MIC for most strains ranged from 6.0 to 25.0 micrograms/ml. The BACTEC radiometric method is a reliable, rapid, and convenient method for preliminary screening and determination of the level of antibacterial activity of drugs not commonly used against M. tuberculosis.

Biotransformation↗
PubMed1987

Ion pair high-performance liquid chromatographic assay for ceftriaxone.

We developed a high-performance liquid chromatographic assay to measure ceftriaxone in serum, urine, and cerebrospinal fluid. Ion pairing was used because ceftriaxone is a relatively polar compound which is poorly retained on C18 columns in standard reverse-phase high-performance liquid chromatography and which produces trailing peaks in the absence of ion-pairing agents. The mobile phase was a combination of acetonitrile and water (46:54), adjusted to pH 9.0 with 10 mM K2HPO4, which contained 10 mM hexadecyltrimethylammonium bromide as the ion-pairing agent. Moxalactam (200 micrograms/ml) was used as the internal standard. A silica-packed precolumn (3 cm long) was used to prevent rapid deterioration of the analytical column (30 by 0.4 cm) by the alkaline pH of the mobile phase, and it significantly extended the life of the analytical column. The assay was linear with ceftriaxone concentrations of 1 to 250 micrograms/ml (r = 0.999) and correlated well with an agar diffusion bioassay (r = 0.990). Reproducibility was good, with intrarun coefficients of variation from 2.3 to 6.4% and interrun coefficients of variation from 3.2 to 21.4%. The absolute recoveries of ceftriaxone and moxalactam were 91 to 97 and 96 to 98%, respectively. No interferences were observed with more than 40 commonly prescribed drugs, including 10 cephalosporins (cefotaxime, cefoperazone, ceftazidime, ceftizoxime, cefoxitin, cefamandole, cephalothin, cefazolin, cephapirin, and cephalexin), or with sera from patients with renal or hepatic disease.

Ceftriaxone↗