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PubMed1990

Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization.

Although the administration of prophylactic antibodies for intrauterine transfusion is controversial, little information is available regarding placental transfer of antibiotics administered to the mother, or whether the presence of hydrops affects this placental transfer. Sixteen intravascular intrauterine transfusions were performed in 10 patients. Seven (10 procedures) patients were given 2 gm of cefazolin before the procedure and samples were obtained by fetal vascular access. Three patients (six procedures) were given 4 gm of piperacillin and samples were similarly obtained. Specimens were obtained for fetal serum, maternal serum, and amniotic fluid antibiotic concentration. The mean serum cefazolin concentration in hydropic fetuses was 18.04 +/- 3.37 micrograms/ml, and in nonhydropic fetuses the concentration was 21.02 +/- 17.8 micrograms/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 +/- 12 micrograms/ml. The placental transfer of both drugs was similar. We conclude that the transplacental passage of these antibiotics is prompt and that the presence of hydrops does not significantly impair the passage of cefazolin.

Blood Transfusion, Intrauterine↗
PubMed1980

Ocular penetration of cefazolin in humans and rabbits after subconjunctival injection.

We determined the clinical potential of cefazolin by assaying aqueous samples for levels of aqueous penetration of cefazolin in humans and rabbits after subconjunctival injection. Cefazolin is a broad spectrum antiotic that appears to penetrate aqueous humor in bactericidal concentrations after subconjunctival injection and may serve as a useful alternative in patients sensitive to other antibiotics.

Animals↗
PubMed1986

Uptake of benzylpenicillin, cefpiramide and cefazolin by freshly prepared rat hepatocytes. Evidence for a carrier-mediated transport system.

The kinetics and mechanism of the hepatic uptake of beta-lactam antibiotics were studied by using freshly prepared rat hepatocytes. The initial uptake rates of benzylpenicillin and cefpiramide represented both saturable and nonsaturable transport processes, whereas that of cefazolin showed an apparently nonsaturable uptake process within the concentration range below 4 mM. The apparent nonsaturable uptake rate constants for benzylpenicillin, cefpiramide and cefazolin were 0.580, 0.047 and 0.289 nmoles/min/mg protein/mM respectively. The apparent values of Kt and Vmax describing the saturable transport were 0.473 +/- 0.158 mM and 2.02 +/- 0.48 nmoles/min/mg protein for benzylpenicillin and 0.847 +/- 0.254 mM and 0.70 +/- 0.18 nmoles/min/mg protein for cefpiramide respectively. The Arrhenius plot of benzylpenicillin uptake of 200 microM presented a single straight line in the range of 22 degrees-37 degrees with an activation energy of 16.8 kcal/mole. An energy requirement was also demonstrated for benzylpenicillin uptake as metabolic inhibitors (antimycin A, NaCN, rotenone and 2,4-dinitrophenol) significantly reduced the initial uptake rate of benzylpenicillin (P less than 0.05). Uptake of benzylpenicillin (200 microM) was not inhibited by ouabain (1 mM). Benzylpenicillin uptake was inhibited competitively by phenoxymethylpenicillin, cefpiramide and cefazolin with the inhibition constants, Ki, of 0.680, 0.583 and 11.7 mM respectively. Benzylpenicillin also inhibited competitively the uptake of cefpiramide with a Ki of 0.655 mM. From these results it was considered that a carrier-mediated uptake system participates in the hepatic uptake of at least four of the beta-lactam antibiotics examined in this study.

Animals↗
PubMed1986

Broad spectrum antibiotics as short term prophylaxis for elective abdominal hysterectomy: comparison of mezlocillin, cefazolin and placebo.

A prospective randomized placebo controlled double-blind study was conducted in order to evaluate the effect of short term perioperative antibiotic prophylaxis on patients undergoing elective abdominal hysterectomy. Fifty-two patients received 3 doses of 0.5 g cefazolin, 54 patients received 3 doses of 1 g mezlocillin and 53 patients received placebo. Postoperative infectious morbidity and the rate of pelvic cellulitis were significantly lower in either antibiotic group in comparison to the placebo group, but neither drug proved to be superior in this respect. The fever index was significantly lower in the mezlocillin group in comparison to both cefazolin and placebo groups. It was thus concluded that antibiotic prophylaxis has a beneficial effect on patients undergoing abdominal hysterectomy and both drugs--cefazolin and mezlocillin--seem to be equally effective.

Cefazolin↗
PubMed1980

Transplacental passage of cefazolin in the first trimester of pregnancy.

The transfer of cefazolin, an antibiotic compound of the cefalosporin group, through the placental barrier was investigated in the first trimester of pregnancy. All cases were chosen from among women admitted for therapeutic abortion. The test group comprised 70 women, while there were 30 in the control group. The bacteriostatic activity was examined in the amniotic fluid, obtained by the vaginal route as well as the maternal blood, following the i.m. injection of 500 mg cefazolin. Our results indicate that the antibiotic cefazolin crosses the placental barrier, even during the first trimester of pregnancy. However, the concentrations obtained were considerably lower than those observed in the 2nd and 3rd trimesters.

Amniotic Fluid↗
PubMed1985

Comparison of the effectiveness of moxalactam and cefazolin in the prevention of infection in patients undergoing abdominal operations.

Patients undergoing elective intraabdominal operations received a three-dose prophylactic regimen of either moxalactam (83 patients) or cefazolin (98 patients) in a blinded, randomized fashion. There was a 9% overall infection rate with 6% for those in the cefazolin group (6/98), and 12% for those treated with moxalactam (10/83) (p = 0.26). Infection rates stratified by types of surgery were similar for both regimens. The drugs were well tolerated, with minimal side effects. Patients at highest risk of infection were those with obstruction of upper gastrointestinal tract and those with pancreatitis. We concluded that moxalactam was no more effective than cefazolin in preventing postoperative infections in this study population.

Abdomen↗
PubMed1993

Cefazolin compared with cefoxitin for cesarean section prophylaxis: the use of a two-stage study design.

The authors used a two-stage design to compare the risk of endometritis in women undergoing non-elective cesarean section who received cefazolin prophylaxis (n = 481) with those who received cefoxitin prophylaxis (n = 1799). The primary data source for this study was an automated record linkage system which allowed the ascertainment of exposure(antibiotic prophylaxis) and preliminary ascertainment of outcome (post-partum endometritis) on a consecutive sample of women undergoing cesarean section between 1 April 1987 and 30 September 1989. Potentially important covariates not available in the automated data source were sampled by review of complete medical records of a random sample of each exposure-disease category of the cohort. Of the 2280 women studied, 99 (4.3%) developed postpartum endometritis. After control for age, race, anemia, presence of ruptured membranes, parity, labor, number of vaginal examinations and payor status the adjusted odds ratio for cefazolin compared to cefoxitin was 0.95 (95% C.I. 0.5-1.9). The cost of prophylaxis was significantly higher for women who received cefoxitin prophylaxis ($56/patient vs $9.55/patient). These results suggest that cefazolin prophylaxis should be favored over cefoxitin due to lower cost and similar efficacy. This study also demonstrates the efficiency of a two-stage design in the setting where exposure and outcome are available for an entire cohort but information about important covariates is more difficult to obtain.

Adult↗
PubMed2006

Lack of association of Staphylococcus aureus type A beta-lactamase with cefazolin combined with antimicrobial spacer placement prosthetic joint infection treatment failure.

Association of cefazolin treatment failure with type A beta-lactamase-producing Staphylococcus aureus has been suggested. The prevalence of beta-lactamase gene types among 23 methicillin-susceptible S. aureus (MSSA) isolates associated with prosthetic joint infection (PJI) treated with cefazolin was determined using polymerase chain reaction (PCR), and clinical and microbiologic outcomes were assessed. PCR revealed 4 isolates without blaZ, and 12 with type A, 2 with type B, and 5 with type C blaZ. Of 13 patients undergoing resection arthroplasty with subsequent reimplantation, all received antimicrobial spacer placement at resection with or without antimicrobial-impregnated polymethylmethacrylate at reimplantation. All 13 cases had tissue cultures at time of reimplantation that were negative for S. aureus and 11 had histopathology specimens showing no acute inflammation. Of 8 type A cases undergoing reimplantation, all prostheses remained in place at follow-up (median, 798 days; range, 32-927 days). We conclude that type A blaZ is common in MSSA PJI and that cefazolin therapy for blaZ MSSA PJI can be successful when combined with 2-stage reimplantation and local antimicrobial therapy.

Anti-Bacterial Agents↗
PubMed2004

Prophylaxis with cefazolin plus clindamycin in clean-contaminated maxillofacial surgery.

PURPOSE: Infections after maxillofacial surgery are usually due to aerobic and anaerobic gram-positive cocci and gram-negative bacilli. Various antimicrobials, including cephalosporins, beta-lactams/beta-lactamase inhibitors, aminoglycosides, lincosamides, and fluoroquinolones, have been tested for use for perioperative prophylaxis in maxillofacial surgery. However, the best regimen has not been determined. We tested the safety and the efficacy of clindamycin plus cefazolin as perioperative prophylaxis for patients undergoing major maxillofacial procedures. PATIENTS AND METHODS: Intravenous cefazolin and clindamycin in 3 doses were administered to 155 patients undergoing major maxillofacial procedures. After surgery, patients were monitored for the presence of infection and side effects. RESULTS: No patient experienced a fever or infection after surgery. No side effects related to these antibiotics were observed. CONCLUSIONS: The antibiotics used as prophylaxis in maxillofacial surgery should possess an adequate coverage against gram-positive aerobic and anaerobic cocci as well as gram-negative bacilli. Prophylaxis with cefazolin plus clindamycin in major maxillofacial seems safe and effective.

Adolescent↗
PubMed2005

Voltammetric behavior and assay of the antibiotic drug cefazolin sodium in bulk form and pharmaceutical formulation at a mercury electrode.

The electrochemical behavior of the antibiotic drug cefazolin sodium (CFZ) in Britton-Robinson buffers (pH 2-11) at the mercury electrode was studied by means of dc-polarography, cyclic voltammetry, controlled-potential coulometry and square-wave adsorptive stripping voltammetry techniques. A validated square-wave adsorptive cathodic stripping voltammetric procedure was described for the trace determination of cefazolin in bulk form up to limits of detection and quantitation of 2.6 x 10(-10)M and 8.6 x 10(-10)M, respectively. The method was successfully applied for determination of cefazolin in pharmaceutical preparation without the necessity for samples pretreatment or any time-consuming extraction or evaporation steps prior to the analysis.

Anti-Bacterial Agents↗
PubMed1992

Comparative study of single-dose cefotaxime and multiple doses of cefoxitin and cefazolin as prophylaxis in gynecologic surgery.

In this comparative, randomized, multicenter trial, 273 patients scheduled for gynecologic surgery were studied: 87 received a single 1-g dose of cefotaxime 30 minutes before surgery; 81 were given a 1-g dose of cefoxitin 30 minutes before surgery and 1 g every 6 hours for 24 hours after surgery (total dose 4 g); and 105 received a 1-g dose of cefazolin 30 minutes before surgery, followed by 1 g every 8 hours for 48 hours (total dose 6 g). Patients who received cefotaxime had a significantly lower incidence of postoperative fever compared with those treated with cefoxitin or cefazolin (p < 0.01). The incidence of positive urinary cultures was lower in the cefotaxime and cefazolin groups when compared with the cefoxitin group (p < 0.01 and p < 0.05, respectively). The results of this study confirm the efficacy of cefotaxime as prophylaxis in surgical infections and demonstrate that single-dose cefotaxime is more effective than a four-dose regimen of cefoxitin.

Adolescent↗
PubMed2003

The effect of additives on the crystallization of cefazolin sodium during freeze-drying.

PURPOSE: To monitor the phase transitions during freeze-drying of cefazolin sodium (I) as a function of process and formulation variables. METHODS: Aqueous solutions of I were frozen under controlled conditions in the sample chamber of a variable temperature X-ray powder diffractometer (XRD). The instrument was modified so that the chamber could be evacuated and the samples dried under reduced pressures. Thus, the entire freeze-drying process was carried out in the XRD holder with real time monitoring of the phase transitions during the different stages of freeze-drying. RESULTS: When aqueous solutions of cefazolin sodium (10% w/w) were cooled to -40 degrees C, the XRD pattern revealed only the crystallization of ice. Annealing the frozen sample led to the crystallization of I as the pentahydrate. Differential scanning calorimetry revealed that the presence of isopropyl alcohol (IPA) (5% w/w) led to a decrease in the Tg', the glass transition temperature of the system, and lowered the temperature of crystallization. The crystallization was studied at -8 and at -15 degrees C in the XRD, and, as expected, more rapid crystallization was observed at the higher temperature. Primary drying at -8 degrees C led to the dehydration of the pentahydrate, resulting in a poorly crystalline product. Again, XRD permitted real time monitoring of the decrease in intensities of some characteristic peaks of the pentahydrate. The in situ XRD technique also enabled us to study the effects of processing conditions (different primary and secondary drying temperatures) and crystalline bulking agents on the solid-state of I in the lyophile. When I was lyophilized using mannitol or glycine as an additive, without an annealing step, the drug was X-ray amorphous although the additive crystallized. When annealed and freeze-dried, I remained crystalline in the presence of glycine but not in the presence of mannitol. CONCLUSIONS: The in situ XRD technique has enabled us to characterize the phase transitions during freeze-drying of cefazolin sodium in multicomponent systems.

Cefazolin↗
PubMed2001

Bacterial counts in experimental, contaminated crush wounds irrigated with various concentrations of cefazolin and penicillin.

The objective of this study was to determine if three different concentrations of cefazolin and penicillin irrigation solutions reduce quantitative bacterial counts in experimental crush wounds contaminated with multiple species of bacteria. The design used was a randomized, blinded, experimental animal study. An animal bite wound model was created by innoculating crushed incisions with three species of bacteria. Four paravertebral incisions extending to deep fascia were created in each of twelve anesthetized albino guinea pigs. Wound edges were clamped with a hemostat for five seconds to create crushed, devitalized tissue within each wound. Wounds were inoculated with 0.4 mL of a standard solution of Staphylococcus aureus, Bacterioides fragilis, and Pasturella multocida and covered. Four hours after inoculation, each wound was scrubbed for 30 seconds with 20% poloxamer 188 and then irrigated with 100 mL of one of four solutions: normal saline solution (control); cefazolin (CZ) 2 mg/mL, plus penicillin G (PCN) 200 units/mL (low dose); CZ 10 mg/mL, plus PCN 2,000 units/mL (intermediate dose); and CZ 50 mg/mL, plus PCN 20, 000 units/mL (high dose). Investigators were blinded to the solutions used. Wounds were covered with a vapor-permeable dressing. Six days after treatment, each wound was examined for signs of infection and then excised for quantitative bacteriologic analysis. Colony counts were reported as counts per gram of tissue. Wounds in the four irrigation solution groups were compared using ANOVA. A log difference of 3 was considered significant. The average log total bacteria/gram tissue for the four groups were: control, 4.35 (95% CI; 1.01); low dose, 4.09 (95% CI; 1.42); intermediate dose, 4.47 (95% CI; 1.27); and high dose, 3.45 (95% CI; 1.33). No wounds in the high-dose group had any clinical signs of infection, whereas 50% of wounds in the intermediate dose group, 42% in the low dose group, and 33% in the control group had either erythema, induration, or purulence. There were no statistically significant differences in the bacterial counts/gram tissue or clinical infection rates in any of the groups. A formal trend analysis failed to find a significant linear trend for decreasing bacterial counts for either antibiotic. In this experimental bite wound model containing contaminated, crushed tissue, irrigation with various solutions of cefazolin plus penicillin G did not reduce quantitative bacterial counts more than 3.1 log total bacteria/gram tissue.

Animals↗
PubMed1987

[Perioperative antibiotic prophylaxis in heart and vascular surgery. A prospective randomized comparative study with cefazolin and ceftriaxone].

Two different forms of cephalosporin prophylaxis were investigated in a prospective randomized comparative study: a one-day cefazoline prophylaxis (Kefzol 0.5 g every six hours) and a single dose of ceftriaxone (Rocephin 2 g). A total of 541 patients were included in the study over 10 months: 272 in the cefazoline (CFZ) group and 269 in the ceftriaxone (CRO) group. The patients were checked postoperatively for an infection. The total rate of infections was 4.7%; 4.6% in the CFZ group and 4.8% in the CRO group. A wound infection occurred in 1.1% of the cases, in 0.4% of the CFZ group and in 1.8% of the CRO group. Septicemia was diagnosed in 1.5% of the operated patients; in 1.2% of the patients treated with CFZ and in 1.8% of the patients treated with CRO. 1.3% of the patients developed pneumonia, 1.8% in the CFZ and 0.8% in the CRO group. Only one patient had a urinary tract infection (CFZ group). Furthermore, two double infections occurred in the CFZ group. A double infection was observed only once in the CRO group. Fever of unclear etiology developed in 3.6% of the patients in both groups. There was no statistically significant difference with regard to the rate of infection between the two groups. A single administration of ceftriaxone prophylaxis is accordingly just as effective as a one-day cefazoline prophylaxis. Despite reduction of the antibiotic application, the rate of infection has not risen in the last five years. The single application is advantageous compared to longer-term applications.

Cardiac Surgical Procedures↗
PubMed1975

Inactivation of cefazolin, cephaloridine, and cephalothin by methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus.

Cefazolin was more susceptible than cephaloridine and cephalothin to in vitro inactivation by coagulase-positive, penicillinase-producing strains of Staphylococcus aureus. Inactivation (which was greater with methicillin-resistant than with methicillin-sensitive strains) was demonstrated by assay of the antibiotics in broth cultures with simultaneous colony counts and by exposure of the antibiotics to penicillinase powders extracted from S. aureus. Cefazolin was destroyed to a greater extent than was cephaloridine, whereas cephalothin underwent little, if any, destruction. The clinical implications of this degradation, thought by some to be of importance for cephaloridine, might also apply to cefazolin.

Cefazolin↗
PubMed1982

Ocular penetration of subconjunctival oxacillin, methicillin, and cefazolin in rabbits with staphylococcal endophthalmitis.

The concentrations of oxacillin, methicillin, and cefazolin were examined in the infected eyes of pigmented rabbits with Staphylococcus aureus endophthalmitis after a subconjunctival dose of 100 mg. The three drugs had fairly similar ocular pharmacokinetics. The tissue concentration usually peaked within 30 min. Levels in the aqueous humor rose more slowly; the respective maximal concentrations of methicillin, oxacillin, and cefazolin were 72, 1,180, and 111 micrograms/ml. Oxacillin also produced the highest levels in the cornea. Penetration of the vitreous humor was poor with all three drugs, apparently owing to a diffusional barrier in the choroid-retina tissue complex. The respective median vitreous levels of methicillin, oxacillin, and cefazolin were 0.7, 0.6, and less than 0.8 micrograms/ml. These values are close to the concentrations usually required to inhibit S. aureus in vitro. Our results suggest that subconjunctival oxacillin achieves higher concentrations in anterior ocular tissues than do the other two drugs, but more aggressive approaches are necessary in treating endophthalmitis.

Animals↗
PubMed1993

Comparative prophylactic efficacy of cefazolin and vancomycin in a guinea pig model of Staphylococcus aureus wound infection.

The increasing prevalence of methicillin-resistant Staphylococcus aureus as a wound pathogen in some institutions has prompted the use of vancomycin for surgical prophylaxis, although clinical data comparing vancomycin and cephalosporins are not available. A guinea pig model was used to compare the efficacy of vancomycin and cefazolin in preventing intermuscular abscess formation by 7 S. aureus strains. Both antibiotics were administered to achieve peak serum levels at the time of bacterial inoculation, and each remained > 1 micrograms/mL for a comparable duration. Vancomycin provided equivalent protection from infection by 1 methicillin-susceptible strain and significantly better protection against 4 methicillin-susceptible and both methicillin-resistant S. aureus strains. For most strains, the bacterial inoculum with a 50% probability of causing an abscess was 2 to 4 log10-fold higher with vancomycin than cefazolin prophylaxis. Prophylaxis with vancomycin is superior to cefazolin in preventing intermuscular infection by methicillin-susceptible and -resistant S. aureus.

Animals↗
PubMed1983

Comparative penetration of latamoxef (moxalactam) and cefazolin into human knee following simultaneous administration.

The penetration of latamoxef (moxalactam) and cefazolin into cancellous bone was compared in ten adult patients undergoing total knee replacement. Each patient received a ten milligram per kilogram bolus dose of both antibiotics at the induction of anaesthesia. Antibiotic bone concentrations were determined by HPLC. The mean serum concentrations of cefazolin were significantly greater (P less than 0.01) than those of latamoxef at all time periods. The absolute bone concentrations of cefazolin and latamoxef did not differ significantly (P greater than 0.05). The method of simultaneous administration offers significant advantages over the conventional two group study design.

Adult↗