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Comparative tissue distribution of ceforanide, cefazolin, and cefamandole in rats.

The comparative tissue distribution of ceforanide, cefazolin, and cefamandole was determined in rats after subcutaneous doses of 100 mg/kg. Ceforanide had the longest plasma half-life, 0.9 h, versus 0.5 h for cefazolin and 0.4 h for cefamandole, and the highest area under the plasma concentration time curve, 324 micrograms x h per ml, versus 184 micrograms x h per ml for cefazolin and 42 micrograms x h per ml for cefamandole. The peak plasma concentrations of ceforanide and cefazolin were 173 and 140 micrograms/ml, respectively, and were threefold higher than that of cefamandole (49 micrograms/ml). Measureable concentrations of the three compounds were found in the liver, kidneys, lungs, submaxillary glands, cervical lymph nodes, bones, heart, abdominal muscles, eyes, and testes, with cefamandole levels being generally lower and more variable. The peak tissue levels of ceforanide and cefazolin were comparable, within the limit of data variation, and were considerably higher than that of cefamandole. The tissue half-lives of these cephalosporins were similar to the respective plasma half-lives.

Animals↗

Cefazolin and moxalactam pharmacokinetics after simultaneous intravenous infusion.

A high-performance liquid chromatographic method for the measurement of moxalactam concentrations in serum was modified to permit the simultaneous measurement of both moxalactam and cefazolin. We then studied whether the simultaneous administration of both moxalactam and cefazolin to normal subjects would produce profiles of serum concentration versus time which were the same as those obtained after the administration of each drug individually. Six healthy adults received a 30-min infusion of cefazolin (10 mg/kg), followed in 2 days by the same dose of moxalactam. After 2 days, both antibiotics were administered together. A two-compartment model was found to adequately characterize the data, and the serum concentration curve for each drug when given alone was statistically identical to that obtained after simultaneous administration. Cefazolin was found to produce a significantly greater peak serum concentration (105 +/- 14 versus 81 +/- 21 microgram/ml) and a significantly greater area under the curve (218 +/- 42 versus 157 +/- 19 . microgram h/ml). The terminal half-life of moxalactam was not significantly longer than for cefazolin (2.2 +/- 0.6 versus 2.0 +/- 0.6 h, respectively). The method of simultaneous administration may have distinct advantages over conventional methods for studies of comparative tissue penetration.

Adult↗

Randomized comparison of cefamandole, cefazolin, and cefuroxime prophylaxis in open-heart surgery.

A total of 337 patients undergoing coronary artery bypass grafting or cardiac valve replacement were randomly assigned to receive cefazolin (1 g every 8 h [q8h]), cefamandole (2 g q6h), or cefuroxime (1.5 g q12h) as an intravenous antibiotic prophylaxis. All drugs were administered within 60 min before the initial incision and were continued for 48 h postoperatively. No adverse effects related to the study drugs were observed. The percentage of patients with postoperative infection was 9% for the cefazolin group, 6% for the cefamandole group, and 5% for the cefuroxime group or 6.5% overall. There were more infection sites in patients treated with cefazolin than in those treated with cefuroxime (P = 0.05) or cefamandole (P = 0.06). Fewer wound infections occurred with cefuroxime (P less than 0.01) and cefamandole (P = 0.06) than with cefazolin. Analyses of the prophylactic regimens used in this study showed cefazolin and cefuroxime to be less costly than cefamandole.

Adult↗

Novel SHV-derived extended-spectrum beta-lactamase, SHV-57, that confers resistance to ceftazidime but not cefazolin.

A new SHV-derived extended-spectrum beta-lactamase, SHV-57, that confers high-level resistance to ceftazidime but not cefotaxime or cefazolin was identified from a national surveillance study conducted in Taiwan in 1998. An Escherichia coli isolate resistant to ampicillin, cephalothin, and ceftazidime but sensitive to cefoxitin, ceftriaxone, cefotaxime, imipenem, and a narrow-spectrum cephem (cefazolin) was isolated from the urine of a patient treated with beta-lactam antibiotics. Resistance to beta-lactams was conjugatively transferred with a plasmid of about 50 kbp. The pI of this enzyme was 8.3. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 861 bases (GenBank accession number AY223863). Kinetic parameters showed that SHV-57 had a poor affinity to cefazolin. The K(m) value toward cefazolin (5.57 x 10(3) muM) was extremely high in comparison to those toward ceftazidime (30.9 muM) and penicillin G (67 muM), indicating its low affinity to cefazolin. Although the K(m) value of the beta-lactamase inhibitor was too high for the study of catalytic activity (k(cat)), indicating the low k(cat) of SHV-57, the SHV-57 carrier was highly susceptible to a beta-lactam-beta-lactamase inhibitor combination. Comparison of the three-dimensional molecular model of SHV-57 with that of the SHV-1 beta-lactamase suggests that the substitution of arginine for leucine-169 in the Omega loop is important for the substrate specificity.

Cefazolin↗

Activity of cefazolin against dense populations of enterobacteria.

The in vitro activity of cefazolin was assessed by continuous turbidimetric monitoring of cultures of gram-negative bacilli and the results were compared with those previously obtained with other beta-lactam agents using the same strains and methods. Cefazolin was found to induce rapid lysis of ampicillin-susceptible and -resistant strains of Escherichia coli at a lower concentration than any other beta-lactam agent tested; its stability to beta-lactamase, as judged by regrowth studies, was generally considerably greater than that of other antibiotics of this group. Tested against 103 ampicillin-resistant enterobacteria, cefazolin was found to be more active than cephalothin against E. coli, but no systematic increase in susceptibility to cefazolin was seen with other species. A study of cefazolin in an in vitro model which simulates the hydrokinetic features of the urinary bladder showed it to be as active as ampicillin against ampicillin-susceptible E. coli and as active as cephalothin against ampicillin-resistant E. coli.

Cefazolin↗

Use of cefazolin for peritonitis treatment in peritoneal dialysis patients.

For over two decades, intraperitoneal administration of vancomycin and an aminoglycoside has been an accepted regimen for the empiric treatment of peritonitis in the peritoneal dialysis patient, until definite identification of the organism has been made. The recent emergence of vancomycin-resistant organisms has been of great concern in many centers. The current treatment recommendation therefore is to use cefazolin in place of vancomycin. We analyzed peritonitis data from January 1, 1996 to June 30, 1997, prior to switching over to cefazolin. Seventy-five percent (27 episodes) in 1997 as compared to 78% in 1996 were due to gram-positive organisms. Twenty-two percent (8 episodes) were due to gram- negative organisms in 1997, 21% in 1996, and 3% (1 episode) due to yeast in 1997, 3% in 1996. Staphylococcus epidermidis (SE) caused 33% of the gram-positive peritonitis episodes in 1997 as compared to 37% in 1996. Twenty-two percent of the gram-positive episodes were due to Staphylococcus aureus (SA) in 1997 and 46% in 1996. Enterococcal infections were 26% in 1997 and 1% in 1996. All of these were confined to only 1 patient. The antibiogram revealed 100% sensitivity of both SA and SE to vancomycin and 100% sensitivity of SA to cefazolin, but only 11% sensitivity of SE to cefazolin. The same patient population had a 48% sensitivity of SE to cefazolin in 1996, showing a sudden and substantial increase in resistance to SE. Even though SE is thought to be a less virulent organism, treating patients with a high probability of being infected by SE with an antibiotic showing 89% resistance is not warranted.

Cefazolin↗

Bactericidal activity of cefazolin, cefoxitin, and cefmetazole against Escherichia coli and Klebsiella pneumoniae.

The bactericidal activity of cefazolin, cefoxitin, and cefmetazole against clinical isolates of Escherichia coli and Klebsiella pneumoniae was investigated. The mean geometric minimum inhibition concentrations against 200 strains each of the test organisms were lowest for cefmetazole, followed by cefazolin and cefoxitin. The killing activity at 5 and 50 microgram/ml of cefazolin and cefmetazole was almost the same and was superior to that of cefoxitin. In the kinetic model under conditions simulating the serum levels of the two drugs in humans after intravenous injection (1 g), cefazolin was the strongest of the three drugs in bactericidal activity. The results indicate that the highest and most prolonged serum concentrations of cefazolin reflected the strong bactericidal activity and the longest inhibition period of bacterial regrowth.

Cefazolin↗

Compatibility and stability of cefazolin sodium, clindamycin phosphate, and gentamicin sulfate in two intravenous solutions.

We studied the compatibility and stability of clindamycin phosphate admixed with gentamicin sulfate and cefazolin sodium in small-volume diluents under specific storage conditions. In two replicate 100 ml dilutions of NaCl 0.9% injection and dextrose 5% (D5W) injection, clindamycin phosphate 900 mg was admixed with gentamicin sulfate 80 mg and cefazolin sodium 1 g. Drug concentrations were determined at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Clindamycin and cefazolin were assayed by high-performance liquid chromatography and gentamicin was assayed by fluorescence polarization immunoassay. Visual inspections and pH determinations of each solution were performed at each assay time. Test solutions were maintained at constant room temperature and fluorescent lighting. Concentrations of clindamycin and gentamicin remained greater than 90 percent of the original concentrations throughout the study. Cefazolin concentrations dropped below 90 percent in D5W injection at 4 hours after admixture and at 12 hours after admixture in NaCl 0.9% injection. Visual analyses and pH changes revealed no significant changes. The combination of clindamycin phosphate 900 mg, gentamicin sulfate 80 mg, and cefazolin sodium 1 g in D5W 100 ml was found to be compatible for up to 4 hours. The duration of compatibility for these three drugs in 100 ml of NaCl 0.9% was 12 hours.

Cefazolin↗

Comparative distribution kinetics of cefazolin and tobramycin in children.

The time courses of drug concentration in serum after i.v. drip infusion of 2 mg/kg of tobramycin and 25 mg/kg of cefazolin in children were analyzed by model-independent moment analysis. The volume of distribution at the steady state per body weight (Vdss/BW) of tobramycin was in the range of 212 to 335 ml/kg and that of cefazolin was 119 to 156 ml/kg. A plot of the differences of Vdss/BW obtained in the same child for tobramycin and cefazolin against the value of Vdss/BW of tobramycin gave a linear regression line (r = 0.971). The magnitude of Vdss (1) of tobramycin could be well interpreted as corresponding to the extracellular water volume. In the case of cefazolin, the extracellular water space accounts for about 60% of the total distribution volume. The remaining 40% of the total Vdss of cefazolin was considered to be accounted for by the disposing organs.

Blood Proteins↗

Intraperitoneal cefazolin and ceftazidime effects on human peritoneal mesothelial cell release of cancer antigen-125.

BACKGROUND: Intraperitoneal (IP) cefazolin and ceftazidime are recommended as empiric treatment for peritoneal dialysis (PD)-associated peritonitis. Human peritoneal mesothelial cells (HPMCs) may be affected by high IP cefazolin and ceftazidime concentrations. Peritoneal dialysate cancer antigen-125 (CA-125) appearance rate can be used to measure HPMC damage. OBJECTIVE: To determine whether IP cefazolin and ceftazidime increase peritoneal CA-125 appearance rate. METHODS: The study consisted of 2 phases. In phase I, no antibiotic was administered, and in phase II, patients received IP cefazolin and ceftazidime (15 mg/kg rounded to nearest 100 mg). Phase II occurred immediately after phase I. Each phase used a 4-hour dwell time with 2 L of dextrose 2.5% dialysate. Dialysate samples were collected at 0, 0.5, 1, 2, and 4 hours during each phase. Samples were assayed for CA-125, and CA-125 appearance rate was calculated. RESULTS: Thirteen patients were recruited (7 men; aged 44.0 +/-16.0 y). The mean +/- SD (range) CA-125 dialysate concentration after phases I and II were 6.6 +/- 3.7 U/mL (2.3-15.0) and 6.4 +/-3.8 U/mL (1.6-13.8), respectively (p = 0.46). The CA-125 appearance rate after phases I and II were 51.9 +/- 31.3 U/min/1.73 m(2) (13.8-113.0) and 50.5 +/- 32.9 U/min/1.73 m(2) (11.0-104.0), respectively (p = 0.57). The slopes of the regression lines of CA-125 appearance rate were not significantly different between phases I and II. CONCLUSIONS: These findings demonstrate that concurrently administered IP cefazolin and ceftazidime have no effect on HPMC release of CA-125 in non-infected PD patients.

Adult↗

Pharmacokinetics of once daily intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients.

This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 +/- 3.1%, volume of distribution 0.20 +/- 0.05 L/kg, and plasma half-life 39.9 +/- 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 +/- 2.3, 1. 4 +/- 1.1, and 3.5 +/- 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 +/- 14.3 and 31.8 +/- 11. 7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.

Absorption↗

Relevance of in vitro antibacterial activities of cefotiam and cefazolin to their therapeutic effects on experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice.

The MICs of cefotiam and cefazolin against K. pneumoniae DT-S were unaffected by the inoculum size and were 0.1 and 1.56 micrograms/ml, respectively. Bactericidal and bacteriolytic activities of the cephalosporins were more potent in bacterial concentrations of 10(7) colony-forming units (CFU)/ml than in concentrations of 10(8) CFU/ml. Both activities of cefotiam were more markedly influenced by bacterial concentrations than those of cefazolin. Therapeutic activity of cefotiam was about 9 approximately 15 times as potent as that of cefazolin in experimental pneumonia caused by K. pneumoniae DT-S in mice, and this finding was in accordance with the ratio of in vitro antibacterial activities of the two cephalosporins as judged by the MICs or the bactericidal and bacteriolytic activities in bacterial suspension of 10(7) CFU/ml. The range of concentrations of cefotiam which induced cell filamentation in vitro, was wider than that of cefazolin. This difference, however, was not reflected on the therapeutic activities of the two cephalosporins in the model infection. In the pneumonic lungs, definite therapeutic doses of both cephalosporins (80 mg of cefotiam per kg and 640 mg of cefazolin per kg) produced mainly bacteriolysis of the challenge organisms.

Animals↗

[The geriatric pharmacology of cefazolin, cefradin and sulfisomidine].

Clinical pharmacology of 3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-8-oxo-7-(tetrazol-1-ylacetamido)-5-thia-1-azabicyclo-(4,2,0)oct-2-en-carbonic acid (cefazolin) and D-7-[2-amino-(cyclohexa-1,4-dien-1-yl)-acetamido]-3-methyl-8-oxo-5-thia-1-aza-(4,2,0)-oct-2-ene-2-carbonic acid monohydrate (cefradine) was compared in young and old adults without renal disease after i.v. injection of 1 g. Mean serum levels of cefazolin after 4 h and 6 h were significantly higher in old persons (25.0 and 14.7 mug/ml, resp.) than in young persons (16.2 and 7.8 mug/ml, resp.). Serum concentrations of cefradine after 2 and 4 h were found also higher in the aged (11.2 and 4.4 mug/ml, resp.) than in young adults. Half-life of cefazolin was prolonged from normally 94 min to 189 min, half-life of cefradine from 32 min to 72 min. Skin blister fluid punctured once for antibiotic assay contained less cefazolin in old persons (after 4 and 6 h only 22.4 and 17.4 mug/ml, resp.) than in young persons (32.7 and 27.6 mug/ml, resp.). Cefradine levels in skin blister fluid 0.5 and 1 h after i.v. injection showed also a significant difference (11.4 and 11.9 mug/ml, resp.) in old persons, 17.3 and 16.5 mug/ml, resp., in young persons). Elimination constants (alpha, beta, kel, k12, k21) were always lower in geriatric patients. Renal clearance of cefazolin was reduced from 83 ml/min to 43 ml/min, and renal clearance of cefradine from 378 ml/min to 152 ml/min. After i.v. injection of 1 g 6-sulfanilamido-2,4-dimethyl-pyrimidine (sulfisomidine) total content of the drug in blood was higher in elderly people than in young persons, but proportion of acetylated sulfisomidine was nearly the same in both groups (15%). It is supposed that higher serum levels of some drugs in old persons (over 70 years) can be explained by impaired renal excretion and slower tissue penetration of the compound from the blood.

Adult↗

[Rapid determination of cefazolin in porcine serum by high performance capillary electrophoresis].

A rapid high performance capillary electrophoretic method was established to assay cefazolin in porcine blood serum. Porcine serum was deproteined by 60% acetonitrile and superlants were injected with 10 s pressure load. The final assay condition was: 40 cm x 75 microns silica capillary, 50 mmol/L bicarbonate buffer at pH10, 20 kV for 5 min, 254 nm UV detection. The assay was linear within the range of 5-320 micrograms/ml, the intra-day and inter-day relative standard deviations ranged from 1.7% to 8.0%. Analytical recovery of cefazolin was 107.9%, the limit of detection was 1.5 micrograms/ml, the limit of quantitation was 3.6 micrograms/ml. To investigate the pharmacokinetic profile of cefazolin in pig, six adult pigs were injected with 16 mg/kg cefazolin and all data was analyzed by pharmacokinetic software 3P87. Cefazolin metabolism in adult pigs appeared to be a typical two-compartment model with a clearance of 8.43 ml/(kg.min).

Animals↗

Comparison of vancomycin versus cefazolin as initial therapy for peritonitis in peritoneal dialysis patients.

The incidence of peritonitis ranges from 1 episode every 24 patient treatment months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.]. Gram-positive organisms account for over 80% of continuous ambulatory peritoneal dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one episodes of peritonitis in 30 patients studied over 2 years were evaluated. Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of peritonitis and were confirmed by cell count and culture. Baseline cell count, Gram stain, and cultures were obtained, with periodic follow-up. Patients were randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading dose, repeated on day 5 or day 8, depending on residual renal function, for 2 weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every exchange for 2 or 3 weeks, depending on culture results. All patients also received gentamicin 40 mg IP every day until the culture results were available. A similar randomized trial comparing vancomycin and cefazolin in the past used a lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Perit Dial /nt 1991; 11:31-7.]. Peritoneal dialysate fluid cultures revealed 31(60.7%) gram-positive organisms, 7(13.7%) gram-negative organisms, and 2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of peritonitis at our center was 1 episode every 42 patient treatment months. No case of VRE was noted. There was no statistical difference in clinical response or relapse rate for the two protocols. It was the authors' and nurses' observation that patient compliance and satisfaction was better with vancomycin, and the cost per treatment was 23% less than cefazolin. Based on these data we believe vancomycin should still be considered for first-line treatment of PD-associated peritonitis.

Adult↗

A single preoperative dose of cefazolin versus postoperative amoxicillin and gentamycin combination in prophylaxis of orthopaedic and traumatologic surgery.

The use of antibiotic prophylaxis was evaluated in 228 surgical patients. The patients were given either cefazolin preoperatively or amoxicillin + gentamycin postoperatively in a randomized fashion to determine whether cefazolin would demonstrate an advantage over amoxicillin + gentamycin with respect to protection against postoperative wound infection, systemic infection and cost. We also tried to find out if the inflation of a tourniquet would interfere in the incidence of wound infection. Major postoperative wound infections were reduced in the cefazolin treated group (2.56 per cent versus 4.50 per cent). There also was a reduction in minor postoperative wound infections in the cefazolin group when it was compared with the amoxicillin + gentamycin group (6.83 per cent, 13.51 per cent, respectively). No systemic infection was seen in either group. There was no difference between the patients on whom were used tourniquets or not. Analysis of patients' charges suggested that 68.75% of the cost of preoperative antibiotic prophylaxis might be saved by limiting the duration of prophylactic drug administration by cefazolin.

Adolescent↗

Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations. A double-blind randomized trial.

Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin-resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided.

Adult↗

Therapeutic interchange of cefazolin with metronidazole for cefoxitin.

The effects on patient outcome and drug therapy costs of a therapeutic interchange program using a cefazolin and metronidazole combination in place of cefoxitin were studied. A therapeutic interchange program was initiated in which the pharmacy department automatically replaced orders for cefoxitin with orders for a cefazolin and metronidazole combination. Data were compared for 100 consecutive patients who received cefoxitin before initiation of the program and the first 100 patients who received cefazolin and metronidazole as part of the program. The impact of the program on therapeutic efficacy, adverse effects associated with therapy, and drug therapy costs was assessed. The two patient groups were similar in age, gender, and white blood cell count. The failure rates for treatment or prophylaxis of infection did not significantly differ between the groups. Duration of therapy and incidence of adverse effects did not significantly differ between the groups. The average cost saving was +72 per patient for treatment with cefazolin and metronidazole instead of cefoxitin. A program for therapeutic interchange of cefazolin and metronidazole in place of cefoxitin demonstrated equivalent efficacy and adverse effects, as well as considerable cost savings.

British Columbia↗