Cefoxitin

Cefoxitin is a beta-lactam antibiotic derived from cephamycin C, a naturally occurring substance produced by Streptomyces lactamdurans. Its resistance to destruction by beta-lactamases results in a broad spectrum of antibacterial activity which includes anaerobic as well as Gram-positive and Gram-negative aerobic bacteria, including many resistant to cephalothin and other cephalosporins. Given by intravenous or intramuscular injection, cefoxitin is effective against a wide variety of infections caused by Gram-positive or Gram-negative aerobes as well as by anaerobic bacteria. It is generally well tolerated, thrombophlebitis, skin rash and some degree of discomfort after intramuscular injection, being the most commonly reported side effects. Cefoxitin has not been shown to cause adverse effects on renal function.

Cefoxitin is a second generation cephalosporin commonly used to treat anaerobic and mixed infections. The authors reviewed the recently published data about the efficacy of cefoxitin; its utility in different clinical entities, patterns of resistance and resistance mechanisms, indications and reliability of in vitro susceptibility testing. These data indicate the need for determining susceptibility patterns of anaerobics at each hospital and point out to the essential close communication between the microbiologist and clinician to the rational treatment of anaerobic infections.

Cefoxitin was administered by the intramuscular route to 102 patients who had infections of mild or moderate severity. The assessment of clinical and bacteriologic outcome was derived from data for 79 patients. Assessments of tolerance and safety were made for all patients who received 1 g of cefoxitin diluted in 1 ml of 0.5% or 1.0% lidocaine four times daily. Cure or improvement occurred in 45 of 47 patients with skin or soft tissue infections, in all of 16 patients with lower respiratory tract infections, and in 10 of 12 patients with urinary tract infections. One patient developed acute tubular necrosis. Eosinophilia was seen in 7% of patients treated with cefoxitin. The intramuscular preparation was not painful to 96% of the patients. Cefoxitin given by the intramuscular route can be used as an alternative to intravenous cefoxitin for treatment of mild or moderate infections, for continuation of treatment when the intravenous route is not appropriate, and for treatment of ulcers of polymicrobial etiology on ischemic extremities or on extremities of diabetic patients.

Cefoxitin has become one of the most used parenteral antibiotics in the United States, perhaps because of a broad spectrum of activity, including activity against Bacteroides fragilis, which makes the drug suitable for prevention and treatment of intraabdominal and pelvic infections. This review focuses on the use of cefoxitin in obstetric and gynecologic infections, with comparisons to older and newer antibiotics. Numerous studies have shown that cefoxitin is clearly effective; in most of these studies, however, either the initial infection rates were low or the sample sizes were small--circumstances making it difficult to establish the superiority of any one agent. Thus, the necessity of using a drug with activity against B. fragilis for prevention and treatment of pelvic infections has not been proven. Several antibiotics without such activity have been equally effective. Cefoxitin may be of particular value when combined with surgical drainage of pelvic abscesses, infections in which control of B. fragilis may be especially important to outcome.

Cefoxitin, a new cephamycin antibiotic that is active against aerobic and anaerobic bacteria, was studied by 35 investigators in the United States. Of 657 patients eligible for evaluation of efficacy of the compound, 69% were cured and 92% were cured or improved on clinical grounds. Bacteriologic response to therapy with cefoxitin was equally good for infections due to gram-positive cocci (94% cured), gram-negative bacilli (87% cured), and anaerobes (95% cured). Cefoxitin was effective clinically and bacteriologically in the eradication of infections due to organisms resistant to ampicillin, cephalothin, chloramphenicol, tetracycline, and aminoglycosides. Overall rates of favorable response to cefoxitin therapy by disease were: lower respiratory tract infections, 90%; urinary tract infections, 87%; intraabdominal infections, 90%; gynecologic infections, 94%; and septicemia, 84%. Cefoxitin was tolerated well, and major abnormalities of hematologic, hepatic, renal, or central nervous system function were encountered rarely. Resistance to cefoxitin did not develop among gram-negative cocci, anaerobes, or gram-negative bacilli in the medical centers in which the antibiotic was used.

Background:This study aimed to explore inter-individual variability of cefoxitin trough levels, predictors of serum cefoxitin concentration and the probability of target attainment of drug levels above 4 mg/L after pediatric cardiac surgery.Methods:Retrospective study on children scheduled for elective cardiac surgery and having cefoxitin trough levels available up to 24 hours postsurgery.Results:Overall, 68 children (9 neonates, 34 infants, 15 children below or equal to 10 years old and 10 patients above this age) were included. Of these, 16 surgeries were performed off cardiopulmonary bypass and 52 were performed on cardiopulmonary bypass. The free cefoxitin concentrations showed a median (interquartile range) concentration of 1.7 (0.6-4.2) mg/L. The range of cefoxitin concentrations showed a 150-fold and 340-fold variability at cardiac intensive care unit admission and after 24 hours, respectively. The pharmacodynamics (PD) targets of free cefoxitin at 100% of the dosing interval, considering Eucast breakpoints for Methicillin Sensitive Staphylococcus Aureus (4 mg/L) and E.Coli (8 mg/L), were obtained in 28% and 16% of patients, respectively. Patient weight (odds ratio, 0.7; 95% confidence interval, 0.62-0.92; P = 0.006) and serum creatinine concentrations (odds ratio, 25; 95% confidence interval, 18-36; P = 0.004) showed a significant relationship with the PD targets.Conclusions:Cefoxitin trough concentrations vary significantly in the first 24 hours after pediatric cardiac surgery. Both serum creatinine and body weight showed independent associations with cefoxitin concentration. The PD target was not obtained in the vast majority of the explored population, regardless of the target bacteria.

The cephamycins are a family of beta-lactam antibiotics that are produced by actinomycetes and are structurally similar to the cephalosporins. They are characterized by the presence of a 7-alpha-methoxyl group, which confers unusually high resistance to beta-lactamases. Cefoxitin, the first semisynthetic cephamycin, is resistant to almost all beta-lactamases. Cefoxitin retains the 3-carbamoyl group of cephamycin C and thus has excellent metabolic stability. Cefoxitin is bactericidal and almost devoid of any inoculum effect. Active against many cephalothin-resistant gram-negative bacteria, cefoxitin demonstrates a very broad spectrum that includes indole-positive Proteus and many strains of Serratia. In contrast to that of the cephalosporins, cefoxitin's spectrum of activity against anaerobic pathogens includes Bacteroides fragilis. The therapeutic effectiveness of cefoxitin in experimental infections in mice confirms the excellent characteristics of this semisynthetic cephamycin and indicates that it should be a very valuable agent for treatment of bacterial infections.

Background:Available data about pharmacokinetics (PK) of antimicrobials administered as surgical prophylaxis to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) showed that drug concentrations during CPB may be supra or subtherapeutic. The aim of this study was to determine the population PK and pharmacodynamic target attainment (PTA) of cefoxitin during pediatric CPB surgery.Methods:A prospective interventional study was conducted. Cefoxitin (40 mg/kg, up to max 1000 mg) was administered before skin incision. Blood samples were obtained in the operatory room throughout surgery. Population PK, PTA, and safety of cefoxitin were evaluated in neonates, infants, children 10 years old.Results:Forty patients were enrolled. Cefoxitin levels correlated with time from bolus administration (r = -0.6, P = 0.0001) and, after 240 minutes from bolus, drug values below the target (8 mg/L) were shown. Cefoxitin concentrations were best described by a one-compartment model with first order elimination. A significant relationship was identified between body weight, age, body mass index, and serum creatinine on drug clearance and age, body weight, and body mass index on cefoxitin volume of distribution. The PTA for free drug concentration being above the minimum inhibitory concentration of 8 mg/L for at least 240 minutes was >90% in all age groups except in patients >10 years of age (PTA = 62%).Conclusions:Cefoxitin PK appears to be significantly influenced by CPB with generally reduced drug clearance. The PTA was adequately achieved in the majority of patients except in patients >10 years old or longer surgeries.

Cefamandole and cefoxitin, introduced only 7 years ago, are now the most commonly prescribed parenteral antibiotics in the United States. These drugs are similar to the first-generation cephalosporins in toxicity, but their in-vitro spectrum of activity is greater. Their serum half-lives are longer than those of cephalothin and cephapirin but shorter than that of cefazolin. Although cefamandole has been recommended in empiric therapy for patients with community-acquired pneumonia and as a prophylactic agent for patients having various surgical procedures, other regimens are less expensive and just as effective. Cefamandole should not be used to treat intra-abdominal, enterobacter, or ampicillin-resistant Haemophilus influenzae infections. Cefoxitin is effective in the treatment and prevention of mixed aerobic-anaerobic skin and soft-tissue, intra-abdominal, gynecologic, and penicillinase-producing, spectinomycin-resistant Neisseria gonorrhoeae infections. Cefoxitin represents a greater advance than cefamandole in our continuing search for safe and more effective antimicrobial agents.