Administration Of Cephalosporins Research Articles

Regional intravenous versus systemic intravenous prophylactic administration of third-generation cephalosporins (ceftazidime and ceftriaxone) in elective foot surgery

The efficacy of a regional route for antibiotic prophylaxis in elective foot surgery was investigated in 20 patients and compared with the standard systemic intravenous method in 47 patients using two third-generation cephalosporins (ceftazidime and ceftriaxone). Each antibiotic (2 g) was given intravenously as the standard systemic prophylaxis at different intervals (10 min, 20 min, 2 h and 4 h) before tourniquet inflation. The same dose of each antibiotic was injected intravenously distal to the tourniquet after inflation. Samples of fat, skin, muscle and bone were collected from the foot and tissue levels of antibiotics were determined using a microbiological method. Peak tissue levels of the systemic antibiotics were administered 20 min before tourniquet inflation. For all tissue samples the antibiotic levels were significantly higher when the antibiotics were given regionally ( P<0.001). The results of this study suggest that regional administration could be a useful route for prophylaxis during elective foot surgery.

Étude bactériologique des otorrhées purulentes de l'enfant dans un CHU en zone tropicale

Background. - Haemophilus influenzae and S pneumoniae are the most common causative agents of acute otitis media in Europe and the USA. This work aimed to identify the agents in Senegal and to study their sensitivity to antibiotics. Population and methods. - Two hundred and one patients, aged 0 to 15 years, with persistent middle-ear effusion, were included in this study from 1983 to 1993. Purulent samples aspirated from the external canal were analysed for bacteriology and sensitivity testing. Results. - Eighty two percent of cultures were positive for Staphylococcus aureus (37%), Pseudomonas aeruginosa (25%), Proteus (18%) and Klebsiella (8%). Positive cultures were found mainly in children aged between 1 and 5 years. Amikacin and cefotaxim were the most active antibiotics against the majority of strains. Staphylococcus aureus was always resistant to penicillin. Conclusions. - Prevalence of Staphylococcus aureus as the causative agent of persistent middle-ear effusion may be explained by late examination. Its resistance to penicillin favors early administration of third generation cephalosporins or pristanimycin.

Cephalosporin-probenecid drug interactions.

The effect of concurrent probenecid administration on the pharmacokinetics of cephalosporin antibiotics varies with the available cephalosporins. Most cephalosporins are affected to some degree by concurrent probenecid administration, although ceforanide, ceftazidime, ceftriaxone and latamoxef (moxalactam) have no significant changes in pharmacokinetics. For those cephalosporins affected by probenecid, the predominant findings are impairment in renal clearance resulting in increased peak serum concentrations, an increased area under the concentration-time curve (AUC), and both delayed and prolonged recovery of the cephalosporin in the urine. The distribution of the cephalosporins is affected to varying degrees, with reports of increased penetration into ocular, central nervous system and blister fluids noted with some agents. The clinical relevance of the changes in cephalosporin distribution associated with probenecid administration has not been investigated. The dose and timing of probenecid administration appear to be major determinants in any possible interaction. Studies with ceftizoxime and cefoxitin suggest that larger probenecid doses result in greater changes in the pharmacokinetics of cephalosporins. Prolonged probenecid therapy before administration of a cephalosporin did not seem to be as relevant as the probenecid dosage in determining the magnitude of the interaction. Probenecid administration with or immediately before cephalosporin administration appears able to produce these documented changes in cephalosporin pharmacokinetics. The route of administration (oral versus parenteral) of either prolosporin pharmacokinetics. The route of administration (oral versus parenteral) of either probenecid or the cephalosporin does not appear to influence the characteristics of the interactions. The therapeutic efficacy of a combination of a cephalosporin with probenecid has been most thoroughly studied for single-dose treatment of gonorrhoea. The addition of probenecid to cephalosporin therapy results in sustained systemic concentrations adequate for eradication of Neisseria gonorrhoeae. Regimens involving either second or third generation cephalosporins demonstrate good success rates with single-dose therapy. However, the success of ceftriaxone administered alone for treatment of both penicillase-producing and non-penicillase-producing strains of N. gonorrhoeae suggests that the addition of probenecid is unnecessary. The use of probenecid, in combination with cephalosporins, to enhance the treatment of other venereal and systemic infections has preliminary, inconclusive support.

Effect of cephalosporins on gamma-aminobutyric acid receptor binding with or without non-steroidal anti-inflammatory drugs.

Cephalosporins have been well known to have potent convulsant activity. We studied the mechanism of the convulsions induced by cephalosporins. Cefazolin, cephaloridine, cefpirome and cefmetazole inhibited the receptor binding of gamma-aminobutyric acid (GABA), an inhibitory transmitter in the mammalian central nervous system. As fluoroquinolones also inhibited GABA receptor binding and this inhibition was enhanced in the presence of non-steroidal anti-inflammatory drugs (NSAIDs), we studied the effect of cephalosporins on GABA receptor binding in the presence of NSAIDs. The inhibitory activity of cephalosporins was not enhanced in the presence of NSAIDs. These results suggested that cephalosporins might induce convulsions through the inhibition of GABA receptor binding, and that concurrent administration of cephalosporins and NSAIDs might not enhance the convulsant activity of cephalosporins.

Nosocomial bacteremia due to Enterococcus faecalis without endocarditis.

During a 2-year observation period at a 2,200-bed university hospital, bacteremia due to Enterococcus faecalis was observed in 111 patients. Fifty-five patients with nosocomial bacteremia due to E. faecalis could be evaluated. The most common entry sites were the urinary tract (25%), the intraabdominal cavity (13%), and burn and decubital wounds (11%). Bacteremia was preceded by administration of cephalosporins, imipenem, and aztreonam (n = 39); ciprofloxacin (n = 11); and other antibiotics (n = 4). Age, sex, underlying disease, portal of entry, previous antibiotic therapy, and bacteremia due to other organisms had no influence on mortality. Treatment of bacteremia with penicillins (n = 45) and glycopeptides (n = 4) resulted in a mortality rate of 37%. The addition of a high-dose aminoglycoside to a penicillin did not result in a better survival rate.

Nephrotoxicity of a new cephalosporin, DQ-2556, in rats

A single intravenous administration of a new cephalosporin, DQ-2556, at 1200 mg/kg to Sprague-Dawley rats induced proximal tubular necrosis. The histological lesions were not closely correlated with renal cortical concentrations of DQ-2556. Development of renal injuries was examined histologically. The arcuate and cortical radial arteries of the kidneys were constricted immediately after the injection, but then became dilated and showed histological changes: penetration by erythrocytes, edematous thickening, and necrosis in the media. In addition to congestion in the outer medulla, the proximal convoluted and straight tubules exhibited the earliest changes 30 min after the injection, namely, enlargement and rounding of the mitochondria and swelling and irregular arrangement of the microvilli in the epithelial cells. Small necrotic foci of epithelium were observed from 4 hr. They were mainly distributed in the outer cortex and the outer stripe of the outer medulla 24 hr later. In the examination of hemodynamics, DQ-2556 significantly decreased the blood flow with increased vascular resistance in the renal artery during and after a single injection. These changes had disappeared wholly or partially 60 min after dosing commenced. Furthermore, Ca 2+ channel blockers markedly inhibited increases in the serum urea nitrogen and creatinine concentrations and development of the tubular necrosis and the lesions of the arterial walls, which were induced by DQ-2556. These results suggest a possible contribution of the constriction of renal artery to the tubular necrosis.

The case for antimicrobial prophylaxis with caesarean section

INFECTIOUS morbidity complicates between 5 and 85 per cent of caesarean sections. The wide variation in incidence is due to differences in definition, and other variables such as the obstetric population studied, the use of antibiotics, and the type of caesarean section. About one per cent of caesarean sections are complicated by serious infections such as septicaemia, pelvic abscess, or generalised peritonitis. The high incidence of infective complications and the dramatic increase in the incidence of caesarean section delivery in developed countries has focused attention on the use of antibiotic prophylaxis for this operation. There is now a large body of evidence from over 90 controlled trials that show that antibiotic prophylaxis decreases the incidence of infection after caesarean section (Enkin et al., 1989). Most of the evidence emanates from North America and shows that prophylaxis is particularly effective in preventing postoperative endometritis, wound infections and urinary tract infections. In a recent London study, the use of logistic regression analysis confirmed that intravenous cephradine decreases the incidence of infection following caesarean section (Turner et nl., 1990). The evidence available indicates that antibiotic prophylaxis is effective for elective as well as emergency caesarean sections. In order to prevent the transfer of the antibiotic to the fetus there are theoretical advantages to waiting until the umbilical cord is clamped, but administering the antibiotic intravenously after induction of anaesthesia appears to have no adverse fetal effects in practice. Long course antibiotic prophylaxis is marginally more effective than short course prophylaxis. The higher cost, the higher risk of altered vaginal flora with antibiotic resistance, dnd the higher risk of drug side effects means that long course prophylaxis is not justifiable at present. Intravenous administration of antimicrobial agents is more practical than peritoneal irrigation. Thus, the recommended regimen at present is the administration of either intravenous broad-spectrum penicillin or first generation cephalosporins in large doses per-operatively, repeated at 6 and I2 hours postoperatively. The additional use of metronidazole to cover anaerobic organisms has not been shown to make any significant improvement in clinical outcome. Not only has antimicrobial prophylaxis been shown to be clinically effective for patients undergoing caesarean section, but economic evaluations have confirmed that it reduces the financial cost of obstetric care (Mugford et QZ., 1989; Turner et a[., 1990). The exact savings depend on the local costs of hospitalisation and the choice of antibiotics. It is important in addition to remember that the benefits of antibiotic prophylaxis should not lead to any complacency with respect to good surgical techniques.

Nephrotoxicity of a New Cephalosporin, DQ-2556, in Rats

A single intravenous administration of a new cephalosporin, DQ-2556, at 1200 mg/kg to Sprague-Dawley rats induced proximal tubular necrosis. The histological lesions were not closely correlated with renal cortical concentrations of DQ-2556. Development of renal injuries was examined histologically. The arcuate and cortical radial arteries of the kidneys were constricted immediately alter the injection, but then became dilated and showed histological changes: penetration by erythrocytes, edematous thickening, and necrosis in the media. In addition to congestion in the outer medulla, the proximal convoluted and straight tubules exhibited the earliest changes 30 mm after the injection, namely, enlargement and rounding of the mitochondria and swelling and irregular arrangement of the microvilli in the epithelial cells. Small necrotic foci of epithelium were observed from 4 hr. They were mainly distributed in the outer cortex and the outer stripe of the outer medulla 24 hr later. In the examination of hemodynamics, DQ-2556 significantly decreased the blood flow with increased vascular resistance in the renal artery during and after a single injection. These changes had disappeared wholly or partially 60 mm after dosing commenced. Fur thermore, Ca2+ channel blockers markedly inhibited increases in the serum urea nitrogen and creatinine concentrations and development of the tubular necrosis and the lesions of the arterial walls, which were induced by DQ-2556. These results suggest a possible contribution of the constriction of renal artery to the tubular necrosis.

Enterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during Therapy

To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia. Prospective, observational study of consecutive patients with Enterobacter bacteremia. Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers. A total of 129 adult patients were studied. The two main end points were emergence of resistance during antibiotic therapy and death. Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy. More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.

Enterobacter sakazakii Bacteremia in an Adult

We have reported a case of E sakazakii primary bacteremia in an elderly patient in whom evaluation failed to reveal a source of infection. This patient had an uneventful recovery after intravenous administration of a third-generation cephalosporin for 7 days followed by 1 week of oral ciprofloxacin. This excellent response supports the previous suggestion that agents more active against gram-negative bacilli should be considered, despite apparent susceptibility to less active agents. Since this case attests to the pathogenicity of this organism in adults, isolation of the organism from clinical specimens should not be dismissed as contamination.

Biochemical mechanisms of cephaloridine nephrotoxicity in suspensions of isolated rabbit proximal tubules

It is well established that cephaloridine (CLD) can cause renal dysfunction, characterized by decreased glomerular filtration rate, glycosuria, enzymuria and proteinuria in both humans and laboratory animals. These changes are often accompanied histologically by widespread necrosis of the S2 segment of the proximal tubule [l]. Nephrotoxicity is not unique to CLD and is often observed during the preclinical development of other, new /3-lactam antibiotics. Thus, these compounds, as a class, have gained the reputation for being nephrotoxic. There has been considerable progress made on the elucidation of the biochemical mechanisms of B-lactam-induced nephrotoxicity. Studies with CLD have indicated that perioxidative decomposition of membrane lipids may be a key event leading to renal injury. Kuo et al. [2] have presented data suggesting that the pyridinium ring of CLD can undergo redox cycling producing oxygen free radicals leading to glutathione (GSH) depletion, malondialdehyde (MDA) formation and renal necrosis. In contrast, Tune and colleagues have suggested that the nephrotoxic cephalosporins can acylate and inactivate the mitochondrial transporters for anionic substrate uptake and thus limit the entry of succinate into the inner mitochondrial compartment [3]. Although these two theories provide an explanation for many of the renal biochemical changes that can occur following administration of nephrotoxic cephalosporins, there are some questions left unresolved. For example, studies examining lipid peroxidation as a mechanism of CLD nephrotoxicity have been conducted al

Failure of Cephalosporins to Prevent Staphylococcus aureus Surgical Wound Infections

Approximately 35,000 Staphylococcus aureus surgical wound infections occur annually in the United States. To investigate why S aureus causes infection despite the perioperative administration of cephalosporins, we compared 35 methicillin-susceptible isolates recovered from deep wound infections that complicated cefazolin prophylaxis (18 of 1650 patients) and cefamandole prophylaxis (17 of 3702 patients) with 64 colonizing isolates from presurgical patients. Compared with both colonizing and cefamandole-associated isolates, S aureus isolates from cefazolin-associated infections were more resistant to cefazolin by specialized assays. Staphylococcus aureus isolates that produced the A and C variants of staphylococcal beta-lactamase were associated with infections following cefazolin and cefamandole prophylaxis, respectively. These isolates hydrolyze the respective cephalosporins rapidly, suggesting that staphylococcal survival after perioperative prophylaxis may be mediated by in vivo degradation of the prophylactically administered cephalosporin. These data indicate that some S aureus wound infections occur because of deficiencies in antimicrobial effectiveness that are not detectable by routine susceptibility tests. This finding has important implications for the therapy and prevention of S aureus infection.

Five day treatment of pharyngotonsillitis with cefpodoxime proxetil

A ten day course of oral penicillin is still recommended for pharyngotonsillitis with the aim of eradicating Streptococcus pyogenes and preventing rheumatic fever. However there is some evidence that penicillin V therapy is less satisfactory than in former years. Several explanations have been suggested, including inadequate pharmacokinetic properties, poor patient compliance, penicillin tolerance, re-infection and carrier state, and indirect pathogenicity. In this context we evaluated the efficacy of third generation cephalosporins. We have shown that a short course of five days treatment with cefpodoxime is as effective as the ten days of conventional treatment with penicillin in terms of both clinical and bacteriological efficacy. Moreover the possibility of reducing the duration of therapy and the twice daily administration of these new cephalosporins results in better patient compliance with treatment.

Complications of cephalosporin administration: continued

Complications of cephalosporin administration: continued

Complications of cephalosporin administration

Complications of cephalosporin administration

Cephalosporin-induced alterations in erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) colony-forming capacity in canine bone marrow

Cephalosporins are among the safest antibiotics. Nevertheless, hematologic abnormalities ranging from mono- to pancytopenia do occur, albeit infrequently, following their therapeutic use. Similar abnormalities to those reported in people have been seen in dogs given high doses of cephalosporins. As part of a study to define the latter thoroughly, we explored the effects of long-term, high-dose cephalosporin administration on canine marrow erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. Cefazedone (Refosporen, E. Merck, Darmstadt) was administered intravenously at doses of 540 to 840 mg/kg daily to 14 healthy beagle dogs for up to 4 months, or less if hematologic effects were evident earlier. Within 6 to 10 weeks, treated dogs developed pancytopenia ( 5 14 ), thrombocytopenia ( 11 14 ), moderate to severe neutropenia ( 8 14 ), and/or normocytic anemia ( 8 14 ). There was evidence of immune-mediated destruction of peripheral blood cells. All treated dogs exhibited a significant reduction in marrow colony-forming capacity, irrespective of whether peripheral cytopenia was present, with 12 14 showing decreased CFU-GM and 14 14 decreased CFU-E activity. Within a week following cessation of dosing, all affected dogs achieved hematologic remission as defined by restoration of the peripheral blood counts. However, despite this apparent recovery, both CFU-E and CFU-GM activities of the bone marrow remained depressed for at least another 8 moths. We conclude that in dogs prolonged administration of high doses of cefazedone induced a persistent deficit of CFU-E and CFU-GM progenitor cells. The clinical relevance of this, if any, remains to be established.

Enterococcal bacteremia in surgical patients.

In 73 surgical patients enterococcal bacteremia was preceded by antibiotic administration (n = 58), central venous catheters (n = 52), other-organism bacteremia (n = 44), and gastrointestinal tract operations (n = 41). Surgical wounds and urinary tract infections were the most frequent portal of entry. The overall mortality was 42%. The mortality risk was significantly greater in patients with preceding or concomitant gram-positive bacteremia and four or more days of cephalosporin administration prior to enterococcemia. In 21 patients who had been given cephalosporins and who had gram-positive bacteremia, specific antienterococcal therapy resulted in survival in five of nine patients, compared with three of 12 who survived without therapy. Enterococcal bacteremia in surgical patients follows antibiotic administration, central venous catheter use, other-organism bacteremia, and intra-abdominal operations. Preceding or concomitant gram-positive bacteremia defines a subgroup of patients with high mortality who seem to respond to antienterococcal therapy.

Hypotension and Bronchospasm Following Rapid Administration of Cephalosporins

Cook and Fort Worth Children's Hospital, Fort Worth, Texas, and the Department of Anesthesiology, University of Texas Health Science Center, Houston, Texas

Evidence for Impaired Hepatic Vitamin K1 Metabolism in Patients Treated with N-Methyl-Thiotetrazole Cephalosporins

In 8 patients on no oral intake and with parenteral alimentation, administration of cephalosporins with N-methyl-thiotetrazole side chain (moxalactam, cefamandole), was associated with prolongation of prothrombin time, appearance in the circulation of descarboxy-prothrombin (counter immunoelectrophoresis and echis carinatus assay) and diminution of protein C. Acute administration of 10 mg vitamin K1 was followed by the transient appearance of vitamin K1 2,3-epoxide, indicating an impaired hepatocellular regeneration of vitamin K1 from the epoxide. Impaired hepatic vitamin K1 metabolism, tentatively ascribed to the N-methyl-thiotetrazole group, is one (but possibly not the only) cause of bleeding complications and depression of vitamin K1-dependent procoagulants in patients treated with the new class of cephalosporins.

In vitro studies on bacterial colonization. The effects of beta-lactam antibiotics on the growth of Escherichia coli and Pseudomonas aeruginosa in mixed culture.

Many cases of Pseudomonas aeruginosa infection are considered to be secondary superinfections, resulting from bacterial colonization. Such cases of superinfection with P. aeruginosa developing after administration of cephalosporin or penicillin are offering serious clinical problems. To make a fundamental analysis of the development of such superinfections, attempts were made to compare the growth patterns of Escherichia coli and P. aeruginosa in pure and mixed cultures and to determine the effects of cephalothin, cefazolin, cephalexin, and ampicillin on the growth patterns. In mixed cultures, the growth of P. aeruginosa was markedly inhibited by E. coli. The higher the concentration of each of the cephalosporins and ampicillin added to the mixed culture, the smaller the population of E. coli sensitive to these agents. When the population of E. coli became smaller than that of P. aeruginosa, which is resistant to these agents, the latter was restored to the same population level as that in pure cultures. Experimental bacterial colonization, by which the predominant population of E. coli was replaced by that of P. aeruginosa in mixed culture, was brought about more efficiently with the cephalosporins than with ampicillin. This might be accounted for by the difference in minimal inhibitory concentration for P. aeruginosa between ampicillin and the other three agents.