Cefazolin Concentrations Research Articles

Effects of seven antibiotics on the growth and development of Phaenicia sericata (Diptera: Calliphoridae) larvae.

Maggot therapy is used for patients with severe tissue destruction, who often receive antibiotics concurrently. Therefore, we studied the effects on maggots of ampicillin, cefazolin, ceftizoxime, clindamycin, gentamicin, mezlocillin, and vancomycin in concentrations of 1, 10, 100, and 1,000 times the average minimum bactericidal or bacteriostatic concentration against highly susceptible organisms. There was a reduction in larval survival in media with gentamicin at concentrations of 1,000 times the average pharmacologic level, or 4,000 micrograms/ml (2.7% survival), versus lower concentrations (80-88% survival). Maturation of the surviving pupae to adults also was decreased at this concentration. Media with cefazolin concentrations of 100 times the average bacteristatic level, or 800 micrograms/ml, also led to a significant decrease in larval survival (70% versus 80-88%). There were no differences in larval survival, rate of maturation, or pupal weights for organisms reared on media containing ampicillin, ceftizoxime, clindamycin, mezlocillin, or vancomycin. P. sericata matured normally--and thus can be used therapeutically--when exposed to standard pharmacologic levels of the 7 antibiotics tested. Furthermore, the methods employed herein may be helpful to forensic entomologists attempting to develop models for drug ingestion by maggots.

Intravenous cefazolin in penetrating eye injuries

The poor intraocular penetration of systemically administered antibiotics has raised questions regarding their usefulness as prophylactic agents in the management of penetrating eye injuries. Cefazolin was administered intravenously to rabbits with penetrating eye injuries to determine the influence of trauma on ocular pharmacokinetics. Following a standardized penetrating eye injury in 27 New Zealand white rabbits, animals were divided into three groups that received either three, six, or nine doses of intravenous cefazolin every 8 h. Cefazolin levels were then measured in the traumatized eye, the non-traumatized (control) fellow eye, and in the serum of each animal. In the three treatment groups vitreous concentrations of cefazolin were significantly higher in traumatized eyes than in the non-injured eyes. After three doses, vitreous concentrations of cefazolin in traumatized eyes averaged 9.1 mg/l; mean concentrations of cefazolin in non-injured eyes were 0.6 mg/l (P < 0.0002). After six doses of intravenous cefazolin, vitreous concentrations in traumatized eyes averaged 7.3 mg/l; cefazolin levels in non-injured eyes were 0.6 mg/l in the non-traumatized eyes (P < 0.0005). After nine doses, vitreous cefazolin concentrations in traumatized eyes averaged 9.7 mg/l, while mean levels in the non-traumatized eyes were all 0.05 mg/l (P < 0.0002). This work suggests that penetrating injuries of the eye alter ocular pharmacokinetics, resulting in high intraocular concentrations of systemically administered cefazolin.

Single-dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection.

The pharmacokinetic properties of cefazolin in the synovial fluid of the tibiotarsal joint were determined in 10 healthy mature cattle after intravenous regional injections of 250 mg cefazolin. A pneumatic tourniquet was positioned proximal to the tibiotarsal joint and the intravenous injection was performed distal to the tourniquet. Synovial fluid concentrations of cefazolin increased in the first 30 min and fluctuated between 54.7 +/- 11.0 micrograms/ml (mean +/- SEM) and 73.2 +/- 13.2 micrograms/ml in the following 90 min while the tourniquet remained inflated. After tourniquet removal, synovial fluid concentration-time curves followed first-order one-compartment model decay in most of the animals with an elimination half-life of 0.82 h (harmonic mean). Therapeutic concentrations of cefazolin in the synovial fluid of normal joints were reached and this injection technique could be used as an alternative to systemic administration of antibiotics to provide adequate concentrations in a localized area.

Cefazolin antibacterial activity and concentrations in serum and the surgical wound in dogs

Summary An antibiotic selected for surgical antimicrobial prophylaxis must be present in the surgical site throughout the operation in concentration sufficient to prevent growth of contaminating pathogens. The antimicrobial spectrum, minimal toxicity, and low cost of cefazolin make this first-generation cephalosporin a logical choice for antimicrobial prophylaxis in small animal surgical procedures in which the normal microbiologic flora of skin and gastrointestinal tract are the most likely pathogens. Pharmacokinetic variables of cefazolin were determined in serum and surgical wounds in dogs. Drug concentration in interstitial fluid of muscle biopsy specimens taken at random from wound surfaces and in postoperative wound fluid samples were determined. Effective surgical wound concentration of cefazolin was defined as 4 μg/ml, a concentration that inhibited the growth in vitro of 100% of staphylococcal and 80% of Escherichia coli clinical isolates. After iv and sc administrations, cefazolin equilibrated rapidly between serum and the surgical wound, and concentrations in the 2 sites decreased in parallel. With a bolus dose of 20 mg/kg of body weight given iv at the beginning of surgery and repeated by sc administration at 6 hours, cefazolin concentration in the surgical wound remained &gt; 4 μg/ml for longer than 12 hours.

Beta-Lactamase-mediated inactivation and efficacy of cefazolin and cefmetazole in Staphylococcus aureus abscesses.

12694668 Clinical reports and animal models have demonstrated that cefazolin may have decreased efficacy against some strains of Staphylococcus aureus because of type A beta-lactamase-mediated hydrolysis. We sought to measure biologically active cefazolin concentrations within abscesses with high concentrations of S. aureus and compare the concentrations with those of cefmetazole, a beta-lactamase-stable cephamycin. A type A beta-lactamase-producing strain of S. aureus with a demonstrated inoculum effect against cefazolin (MIC at an inoculum of 5 x 10(5) CFU/ml, 1.0 micrograms/ml; MIC at an inoculum of 5 x 10(7) CFU/ml, 32.0 micrograms/ml) but not cefmetazole (MICs at inocula of 5 x 10(5) and 5 x 10(7) CFU/ml, 2.0 micrograms/ml) was used. Cefazolin or cefmetazole (100 mg/kg of body weight every 8 h for 8 days) was administered to rabbits with infected tissue cages. No differences in the concentrations of the two drugs in the uninfected tissue cages were observed. Higher concentrations of cefmetazole than cefazolin were found in infected tissue cages at day 3 (5.9 +/- 0.7 versus 2.2 +/- 0.3 micrograms/ml; P < 0.01), day 5 (9.1 +/- 2.6 versus 3.6 +/- 0.7 micrograms/ml; P = 0.02), and day 8 (9.4 +/- 1.4 versus 4.8 +/- 0.9 micrograms/ml; P = 0.01) after infection. Cefazolin and cefmetazole were equally effective in reducing the bacterial concentration in the abscess. In vitro experiments demonstrated greater cefazolin than cefmetazole degradation by S. aureus, but the differences were greater in serum than in abscess fluid supernatants. We conclude that abscess cefazolin concentrations are diminished by type A beta-lactamase-producing S. aureus, but this did not affect drug efficacy in this model.

Human intradiscal levels with cefazolin.

The administration of prophylactic antibiotics for the prevention of discitis is common in the field of spinal surgery. The purpose of this study was to determine 1) whether cefazolin administered intravenously would result in detectable intradiscal levels; and 2) if so, what the proper timing of the antibiotic bolus should be to achieve optimal intradiscal concentrations. Forty human lumbar discs were obtained during the study period. All subjects received a preoperative bolus infusion of 2 g of cefazolin during a 3-5 minute period. Serum and intradiscal samples were obtained at intervals ranging from 6 to 220 minutes after the antibiotic infusion. The respective intradiscal concentrations of cefazolin were then determined, and the findings were as follows: 1) cefazolin does diffuse into the human disc in detectable concentrations; and 2) a critical time relationship exists (15-80 minutes after a bolus administration of cefazolin) for the optimal level of intradiscal antibiotics to be achieved.

Effect of Gastrointestinal Maturation on Absorption of β‐lactam Antibiotics

Gastrointestinal absorption of cefazolin, which is poorly absorbed in adults, and of cephradine, which is well absorbed in adults, was studied in rats during their development. Significantly higher concentrations of cefazolin in plasma after oral administration were observed in 1‐ and 2‐week‐old rats compared with 3‐week‐old and adult rats. A marked difference in the absorption of cefazolin by 2‐ and 3‐week‐old rats (at weaning period) was observed. No such marked difference in the absorption of cephradine by rats of various age groups was found. With cefazolin, a similar pattern of developmental change in jejunal uptake was observed. Cortisone, which causes early maturation of the intestinal membrane, was given as a preweaning injection to 2‐week‐old rats. This treatment decreased concentrations of cefazolin in plasma and jejunal uptake of cefazolin. Thus, the absorption of cefazolin in 1‐ and 2‐week‐old rats seems to depend on the permeability of the immature intestinal membrane before weaning. Cephradine absorption from the intestine of 1‐week‐old rats became saturated and inhibited by camosine and glycylglycine when studied by the in situ loop method. Cefazolin absorption was proportional to luminally administered doses and was not affected by carnosine and glycylglycine. A nonsaturable process tor csfazolin and a saturable process for cephradine were also observed in an in vitro uptake experiment.

Pharmacokinetic disposition of cefazolin in serum and tissue during canine total hip replacement.

Intraoperative cefazolin concentrations were measured in serum, joint capsule, cancellous bone of the acetabulum, and proximal cancellous bone of the femur in 15 dogs undergoing total hip replacement. Cefazolin (22 mg/kg intravenously [IV]) was administered every hour for three doses. The mean peak serum concentrations (+/- SEM) were 387.79 +/- 27.56 micrograms/mL, 521.71 +/- 28.00 micrograms/mL, and 542.20 +/- 30.91 micrograms/mL, respectively. Mean serum concentrations just before administration of doses 2 and 3 were 51.77 +/- 2.39 micrograms/mL, and 64.84 +/- 3.46 micrograms/mL, respectively. The mean cefazolin concentrations in the joint capsule, cancellous bone of the acetabulum, and cancellous bone of the femur were 34.71 +/- 2.50 micrograms/g, 28.70 +/- 7.40 micrograms/g, and 36.20 +/- 3.80 micrograms/g, respectively. The minimum inhibitory concentration of cefazolin for 90% of the common contaminants (MIC90) in this clinic is less than or equal to 2 micrograms/mL or per gram of tissue. Serum concentrations never fell below 15 times the MIC90 (lowest trough, 35.93 micrograms/mL), and the lowest tissue concentration (6.57 micrograms/mL in cancellous bone from the acetabulum) was still more than 3 times the MIC90. The mean tissue concentration was 15 times the MIC90.

Moment analysis of drug disposition in kidney. VI: Assessment ofin vivo transmembrane transport ofp-aminohippurate in tubular epithelium

This paper describes a novel method to assess the antiluminal membrane (ALM) and luminal membrane (LM) transport in vivo across renal tubular epithelial cells. The method is based upon a noncompartmental moment analysis of the plasma concentration and urinary excretion rate curves following renal artery injection. Quantitative relationships are represented between the noncompartmental parameters (clearance, volume of distribution, and the mean transit time) and the first-order rate constants associated with transmembrane transport processes. The in vivo transepithelial transport of [14C]p-aminohippurate (PAH) was examined using the rat kidney in the absence or presence of various plasma concentrations of unlabeled PAH, cefazolin, and methotrexate. The tubular secretion intrinsic clearance was reduced with an increase in the plasma concentration of concurrent unlabeled organic anions. The distribution volume of PAH in the kidney decreased in association with a decrease in the amount of PAH secreted, whereas the mean transepithelial (artery-to-lumen) transit time (Tcell) remained constant. These findings indicate that ALM transport is a capacity-limited process determining the amount of tubular secretion, and that LM transport is linear over the concentration range examined and independent of the amount of secretion. The contribution of ALM and LM transport to transcellular transport was first clarified in vivo. The present method will be useful for analyzing the transmembrane transport processes in vivo for highly diffusible substances in the kidney.

Effect of controlled hemorrhage on tissue and serum cefazolin clearance

Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits. Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels. Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion. Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat ( P ⩽ 0.01) and artery ( P ⩽ 0.01) at 90 min. Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I ( P ⩽ 0.05), Group III to I ( P ⩽ 0.01), and Group IV to V ( P ⩽ 0.01). The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals. More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage.

Stability of cefazolin sodium in peritoneal dialysis solutions

The stability of cefazolin sodium was studied in two commonly used peritoneal dialysis solutions. Cefazolin (as the sodium salt) 250 mg was added to 500-mL bags of dialysis solution containing 1.5% or 4.25% dextrose injection to yield a target concentration of 0.5 mg/mL. Of 18 bags containing 1.5% dextrose injection, six were stored at 4 degrees C, six at 25 degrees C, and six at 37 degrees C. Similarly, of 18 bags containing 4.25% dextrose injection, groups of six were stored at each temperature. Samples were measured for cefazolin concentration by high-performance liquid chromatography at 0, 3, 7, 10, and 14 days for solutions stored at 4 degrees C; 0, 1, 2, 3, 8, and 11 days for solutions stored at 25 degrees C; and 0, 6, 12, and 24 hours for solutions stored at 37 degrees C. The cefazolin concentration in both solutions was greater than or equal to 90% of the initial concentration for 14 days at 4 degrees C, 8 days at 25 degrees C, and 1 day at 37 degrees C. On day 11 at 25 degrees C, however, the loss of cefazolin was 11% for the solution containing 1.5% dextrose injection and 15% for the 4.25% dextrose injection. The sterility of the solutions was not determined. Cefazolin sodium was stable in peritoneal dialysis solutions containing 1.5% and 4.24% dextrose injection for 14 days at 4 degrees C, 8 days at 25 degrees C, and 24 hours at 37 degrees C.

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Limited information is available on the pharmacokinetics and tissue penetration of cefazolin in pediatric patients. Nine children (age 0.8-10 years) undergoing gastrointestinal operations were studied. A single dose of cefazolin, 15-26 mg/kg was given i.v. over 2-3 min at the time of induction of anaesthesia. Multiple (5-8) blood samples were collected during the operative procedure and in the recovery room. Tissue samples from the rectus abdominis muscle were obtained at the time of incision, during surgery, and at closure. The concentration of cefazolin was measured by a high performance liquid chromatographic method. Peak serum concentrations of cefazolin ranged from 85.8-269.4 mcg/ml. Serum and tissue concentrations at incision were 50.5-169.9 mcg/ml and 1.8-29.7 mcg/g; at closure the serum and tissue concentrations ranged from 17.3-60.9 mcg/ml and 1.19-29.70 mcg/g, respectively. Total clearance, apparent distribution volume, and elimination half-life of cefazolin were 1.43 +/- 0.54 ml/min/kg, 0.08 +/- 0.03 l/kg, and 1.68 +/- 0.55 h respectively. Tissue concentrations of cefazolin were maintained above its minimum inhibitory concentrations against common susceptible pathogens. Hence, the current dosing regimen of cefazolin is adequate to protect against infection in pediatric patients undergoing gastrointestinal surgery.

Antibiotic Prophylaxis and Tourniquet Inflation in Total Knee Arthroplasty

Twenty-four patients receiving total knee arthroplasty (TKA) were randomized into one of three groups based on tourniquet inflation one, two, or five minutes after administration 1 g cefazolin. Simultaneous serum, soft-tissue, and bone samples were obtained at regular intervals during surgery. All soft-tissue and bone samples were corrected for cefazolin content. The percentage of cefazolin penetration into soft tissue and bone was calculated using the area under the concentration time curve. Adequate cefazolin concentrations for soft tissue and bone were defined as greater than or equal to 4 x minimum inhibitory concentration90 (MIC90 = 1 microgram/ml) of cefazolin to Staphylococcus aureus and coagulase-negative staphylococci. Patients were similar in age, actual body weight, creatinine clearance, and length of tourniquet inflation. The median percentage of cefazolin penetration into soft tissue and bone for the five-, two-, and one-minute groups was 14.5% and 4.6%, 6.7% and 3.0%, and 5.9% and 4.6%, respectively; the percentage of penetration into soft tissue between the five- and one-minute groups was statistically significant. A higher percentage of patients achieved the desired cefazolin concentration (greater than or equal to 4 micrograms/g) if a five-minute interval was selected. The five-minute group achieved the highest mean ratios of concentration to MIC compared with the two- and one-minute groups, although the differences were not statistically significant. The standard 1 g of cefazolin with a five-minute interval between administration and tourniquet inflation resulted in adequate mean soft-tissue and bone concentrations for prophylaxis during TKA with a tourniquet time less than two hours. Additional doses are not warranted after tourniquet release.

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 (ig/ml, and in nonhydropic fetuses the concentration was 21.02 ± 17.8 µg/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 ± 12 (xg/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.

Assessment of cefazolin and cefuroxime tissue penetration by using a continuous intravenous infusion

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) or cefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations of cefazolin (at incision, 9.3 micrograms/ml; at closure, 9.2 micrograms/ml) and cefuroxime in serum (at incision, 26.9 micrograms/ml; at closure, 31.8 micrograms/ml), there was no difference in the total concentrations in muscle at either surgical incision (cefazolin, 6.1 micrograms/g; cefuroxime, 5.6 micrograms/g) or wound closure (cefazolin, 7.7 micrograms/g; cefuroxime, 7.4 micrograms/g). There was a significant correlation between the pooled free serum and total muscle concentrations for cefazolin (P = 0.001); however, there was no correlation between these variables with the pooled cefuroxime data (P = 0.403). These findings indicate that the free drug concentration in serum alone is not consistently predictive of the total concentration of cephalosporin in muscle.

Impact of postantibiotic effect on bacterial adherence to vascular prostheses

The brief exposure of bacteria to high antibiotic concentrations can result in prolonged suppression of bacterial growth termed postantibiotic effect (PAE). Apathogenic Staphylococcus epidermidis strain (RP-62) was exposed to 2× and 6× minimum inhibitory concentrations (MIC) of cefazolin, vancomycin, or rifampin for 1 hr and incubated for 2 to 24 hr in inhibitory-free broth. PAE was defined as the difference in time required for a 1.0 log increase in test ( T) vs control ( C) cultures (PAE = T - C). PAE was observed only for rifampin: 6 hr at 2× MIC and 8 hr at 6X MIC. Bacterial adherence to Dacron grafts was calculated in PAE vs control cultures by a quantitative culture technique for graft specimens incubated 2 to 24 hr. A demonstrable PAE and its impact on adherence were found to be both antimicrobial and concentration dependent. A significant decrease in staphylococcal adherence to velour-knitted Dacron was demonstrated by rifampin at 2X MIC ( P < 0.05) and 6X MIC ( P < 0.01). This phenomena may be useful in reducing bacterial adherence and colonization of bioprosthetics in the perioperative period. Preoperative suppression of staphylococcal skin flora by high dose antimicrobials can alter the capacity of these organisms to adhere to vascular prosthetic grafts and, if incorporated into antibiotic prophylaxis regimens, may reduce graft colonization.

Alternative Activity of -Lactam Antibiotics against Methicillin- and Cephem-Resistant Staphylococcus aureus in the Presence of Respiratory Tract Mucus

Methicillin- and cephem-resistant Staphylococcus aureus (MRSA) strains were found to be unable to grow in sputum from patients treated with a beta-lactam antibiotic. Sputum containing no beta-lactams also exhibited bactericidal activity when the MRSA strain was pretreated with a subinhibitory concentration of a beta-lactam; however, lysozyme-free sputum was inactive. Peptidoglycan of MRSA grown in the presence of cefazolin was susceptible to lysis by respiratory mucus. Hen albumen lysozyme contained the same activity against beta-lactam-treated MRSA. The median minimum inhibitory concentration of cefazolin for 45 S. aureus strains (including 20 MRSA strains) shifted from approximately 50 micrograms/ml to approximately 0.78 microgram/ml by addition of 1 mg/ml of hen albumen lysozyme to susceptibility-testing media. Such lysozyme-dependent antistaphylococcal activity was manifested specifically with beta-lactams (9 penicillins, 10 cephalosporins, 3 cephamycins, 1 oxacephem, and 1 carbapenem).

Efficacy of prophylactic antibiotics in vascular surgery: An arterial wall microbiologic and pharmacokinetic perspective

This prospective study examined microbiologic features of arterial tissue and the pharmacokinetics and bioactivity of cefamandole and cefazolin in patients undergoing elective primary prosthetic aortoiliofemoral/infrainguinal reconstruction. Double-blind, randomized, perioperative prophylaxis (1 gm intravenously every 6 hours for nine doses) with cefamandole or cefazolin was administered to 47 patients. Specimens of blood serum, subcutaneous fat, thrombus, atheroma, and arterial wall were obtained for culture and minimal inhibitory concentration and drug level analysis by high-pressure liquid chromatography. The serum half-life (hr ± SEM) was 1.43 ± 0.36 for cefamandole and 2.22 ± 0.40 for cefazolin. Over the first 2 hours of surgery and for all time intervals combined, the serum concentration of cefazolin was significantly higher (p < 0.025) than cefamandole. Irrespective of sampling time, the tissue concentration of cefazolin was significantly greater (p < 0.005) than cefamandole. Positive arterial tissue cultures were obtained in 12 of 29 patients (41.4%) from 23 of 116 (19.8%) arterial tissue specimens. Coagulase-negative Staphylococcus was the predominant isolate, 64 of 93 (68.8%). Twenty-five of the 51 coagulase-negative staphylocci tested (49%) were slime-producers. During surgery, the arterial tissue concentration of cefamandole fell below the geometric mean minimal inhibitory concentration against all organisms combined, and against S. aureus (with the highest minimal inhibitory concentration of the prevalent isolates), significantly more often than the concentration of cefazolin. The data show that a significant number of primary elective aortoiliofemoral/infrainguinal reconstructions are associated with positive arterial tissue cultures, which represent a potential source of graft infection. For adequate antibiotic prophylaxis during major vascular reconstructions, our data suggest that both cefamandole and cefazolin should be administered in higher doses and at more frequent intervals than is currently recommended.

Penetration of prophylactic antibiotics into peritoneal fluid

This study evaluates the penetration of cephalosporins into the peritoneal fluid. Forty-six patients scheduled for abdominal surgery were randomized into three groups. On call to the operating room each patient was given a single 1 g dose of cefazolin, cefuroxime, or ceftazidime. Samples of the peritoneal fluid and blood were simultaneously obtained immediately after opening the peritoneal cavity. The mean serum cefazolin concentration was the highest. High peritoneal fluid levels of all three antibiotics were found; however, the antibacterial activity against common intestinal pathogens varied significantly. Cefazolin is the only study drug that-possesses marginal in vitro activity against Streptococcus faecalis, a species generally considered resistent to cephalosporins. This study suggests that prophylactic second and third generation cephalosporins are not superior to cefazolin.

Penetration of antibiotics into the surgical wound in a canine model.

The dose and timing of antimicrobial agents given for surgical wound prophylaxis should be based on the concentration-time profile of the drug in tissue at the site of contamination. However, concentrations of antimicrobial agents in surgical wounds are difficult to determine accurately. Since a surgical wound is a unique extravascular compartment with increased vascular permeability and a high surface area/volume ratio, antibiotic concentrations in sera and surgical wounds should be similar. To test this hypothesis, the pharmacokinetics of single intravenous doses of cefazolin (40 mg/kg) and gentamicin (4 mg/kg) in sera and surgical wounds in a clinically relevant surgical model using dogs were compared. Drug concentrations were determined in interstitial fluid in muscle biopsies taken randomly from wound surfaces and serial wound fluid samples collected after the incisions were closed. Protein binding of cefazolin and gentamicin in sera and wound fluids was low (less than or equal to 29 +/- 9%) in this canine model. Cefazolin and gentamicin equilibrated rapidly (less than or equal to 30 min) between serum and the surgical wound, and concentrations in the two sites declined in parallel. Values for the area under the concentration-time curve, mean residence time, and terminal half-life in serum and the surgical site for each drug were similar. Cefazolin concentrations in serum underestimated the time during which concentrations in surgical wounds exceeded the susceptibility breakpoint MIC for important pathogens by an average of 58 min (range, 26 to 109 min; P = 0.036); for gentamicin, the underestimation averaged 30 min (range, 10 to 60 min; P = 0.036). These data support the concept that the concentration-time profiles of antimicrobial agents in serum may prove valuable clinically as guides to determining the and timing of antibiotic administration necessary for effective antimicrobial prophylaxis in surgery. Further studies are needed to determine the surgical wound pharmacokinetics of highly protein-bound antibodies.