Cefazolin Levels Research Articles

Serum levels of prophylactic cefazolin during cardiopulmonary bypass surgery

Background Controversy exists regarding the appropriate prophylactic dose of cefazolin for coronary artery bypass grafting (CABG) surgery requiring cardiopulmonary bypass (CPB) because the effect of CPB on serum drug levels is poorly understood. Current standards of prophylaxis are based primarily on empiric studies. Few studies have attempted to quantify serum cefazolin levels in either cardiac or noncardiac surgeries. This study was conducted to measure and assess the adequacy of the intraoperative serum levels of prophylactic cefazolin in CPB surgery. Methods This prospective study serially measured six intraoperative serum cefazolin levels in 10 subjects undergoing elective and urgent CABG surgery. We compared the serum levels with the minimum inhibitory concentrations (MIC 90) for the most common organisms causing postoperative infection. Results Serum-free cefazolin levels fluctuated considerably during the operation but remained above the MIC 90 for Staphylococcus aureus and S. epidermidis. The serum levels fell below the MIC 90 for Enterobacter, Serratia, Escherichia coli, and Proteus mirabilis. Conclusions Serum cefazolin levels during CPB remained consistently above the MIC for two of the three main organisms causing postoperative infection but were suboptimal for the remainder. Additional studies are needed to assess the intraoperative serum levels of single-dose cefazolin prophylaxis and to explore alternate dosing methods that minimize intraoperative fluctuations in serum cefazolin levels.

Maternal and transplacental pharmacokinetics of cefazolin

OBJECTIVE: To evaluate the intrapartum pharmacokinetics of cefazolin, including delivery to amniotic fluid (AF) and fetal compartments, and to ascertain that adequate cefazolin concentrations are attained to exceed the mean concentration inhibiting 90% (MIC 90) of group B streptococcus strains. METHODS: Cefazolin (1 g) was administered intravenously at five separate time intervals (0.5, 1, 2, 4, and 6 hours) before elective cesarean at term to 26 women with intact membranes and with no significant infections or cardiovascular, liver, or renal disease. Samples of maternal blood, cord blood, and AF were obtained at the time of delivery. Exact collection times relative to cefazolin infusion were noted. Amniotic fluid contaminated with blood or meconium was excluded. Cefazolin concentration was measured by high-pressure liquid chromatography. RESULTS: All maternal and cord plasma cefazolin levels, except one, were above the MIC 90 for Streptococcus agalactiae (group B streptococcus). For AF, all cefazolin levels, except two, were above the MIC 90. CONCLUSIONS: Cefazolin concentrations greater than or equal to the MIC 90 for group B streptococcus were attained in nearly all maternal, fetal, and AF samples. This information, together with the knowledge that there is rare resistance of group B streptococcus to cefazolin, supports the use of cefazolin as a better alternative than clindamycin or erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy.

Pharmacokinetics of Intraperitoneal Cefazolin and Gentamicin in Empiric Therapy of Peritonitis in Continuous Ambulatory Peritoneal Dialysis Patients

The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate cefazolin and gentamicin in Thai continuous ambulatory peritoneal dialysis (CAPD) patients treated following the International Society for Peritoneal Dialysis (ISPD) 1996 recommendations for the empiric therapy of CAPD-related peritonitis. Prospective and descriptive study. Institutional level of clinical care. CAPD-related peritonitis patients were diagnosed by dialysate effluent white cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50%. There were 18 patients, all at least 15 years of age, entered; all completed the study. In accordance with the ISPD 1996 recommendations, the antibiotic regimen included continuous intraperitoneal (IP) cefazolin and once-daily IP aminoglycoside. Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate, respectively. Gentamicin, 0.6 mg/kg body weight, was given IP once daily. Duration of treatment was 120 hours. Serum and dialysate effluent samples of the 18 CAPD patients with peritonitis were measured and used for the synthesis of pharmacokinetic equations that could predict drug concentrations at any treatment time. Following administration according to the ISPD 1996 treatment recommendations, serum cefazolin reached levels higher than the recommended levels (8 microg/mL) at 3.3 minutes after drug administration, and persisted through the 5-day duration of the study. Dialysate cefazolin levels during the studied period also were persistently higher than the recommended values. The peak serum gentamicin levels were lower than the suggested values of 4 microg/mL, whereas the trough serum gentamicin levels were higher than the minimal toxic concentrations (2 microg/mL). Dialysate gentamicin levels were higher than therapeutic concentrations for only 4.75 hours in each day. It was difficult, using pharmacokinetic studies, to adjust the dosage regimen of gentamicin to achieve appropriately therapeutic levels in both serum and dialysate. The ISPD 1996 recommended dosage of continuous IP cefazolin could be appropriate for the treatment of CAPD-related peritonitis. Once-daily IP gentamicin administration, however, has less therapeutic benefit and should be re-evaluated.

Simultaneous determination of cefazolin in rat blood and brain by microdialysis and microbore liquid chromatography.

A sensitive microbore liquid chromatographic method combined with the minimally invasive technique of microdialysis was devised for simultaneously and continuously monitoring the levels of unbound blood and brain cefazolin in rats. Microdialysis probes were inserted into the jugular vein and brain striatum for blood and brain sampling, respectively. Chromatographic conditions consisted of a mobile phase of methanol-acetonitrile-100 mM monosodium phosphoric acid (20:10:70, v/v, pH 4.5) pumped through a microbore reversed-phase column at a flow rate of 0.05 mL/min. The ultraviolet detection wavelength was set at 270 nm. An on-line design allowed direct and continuous analysis of protein-free samples in the dialysate. Microdialysis probes, being home-made, were screened for acceptable in vivo recovery. Chromatographic resolution and detection were validated for response linearity as well as intra-day and inter-day variabilities. This method was then applied to pharmacokinetic profiling of protein unbound cefazolin in both the blood and brain following intravenous administration (10 mg/kg, i.v., n = 6). Rapid appearance of cefazolin in the rat brain striatal dialysate following drug injection suggested good blood-brain barrier penetration. According to a non-compartmental pharmacokinetics model, the area under the concentration (AUC) vs time ratio of cefazolin in rat brain and blood was 6%.

Cefazolin in chronic hemodialysis patients: A safe, effective alternative to vancomycin

Vancomycin use is common in hemodialysis patients, due in part to the ease of dosing, but can lead to the development of resistant organisms, including vancomycin-resistant enterococcus. Alternate antibiotics may be equally effective and allow similar dosing in the chronic hemodialysis population. A retrospective review of culture results from a 217-patient, non-hospital-based outpatient hemodialysis center was performed over a 7-month period. Wound and blood culture sensitivity to cefazolin, vancomycin, cefazolin plus gentamicin, and vancomycin plus gentamicin was analyzed. Cefazolin was equivalent to vancomycin for empiric treatment of clinically significant infections in a population with a low rate of methicillin-resistant Staphylococcus aureus infection. Cefazolin plus gentamicin was superior to vancomycin alone. The vancomycin plus gentamicin combination did provide minimally broader coverage than the cefazolin plus gentamicin combination. A prospective pharmacokinetic analysis of postdialysis cefazolin dosing was performed in anuric chronic hemodialysis patients dialyzed with polysulfone dialyzers. Peak, predialysis, and postdialysis cefazolin levels were obtained. Nondialysis clearance of cefazolin was sufficiently low (k(e), 0.027; t(1/2), 26.4 hours) and dialysis clearance sufficiently high (k(e), 0.254; t(1/2), 3.19 hours) to provide for safe and effective peak and trough cefazolin levels with postdialysis dosing in anuric hemodialysis patients. In conclusion, cefazolin alone or with gentamicin in an appropriate empiric antibiotic choice in chronic hemodialysis patients dialyzed in a nonhospital setting with low methicillin-resistant S. aureus infection rates. For infections with documented sensitivity to cefazolin, a 1 g intravenous dose postdialysis (750 mg in patients weighing <50 kg) is safe and effective. (Am J Kidney Dis 1998 Sep;32(3):401-9)

Antibiotic prophylaxis and tourniquet application in podiatric surgery

The use of prophylactic antibiosis in podiatric surgery is common, especially in patients undergoing endoprosthetic procedures, major arthrodeses, lengthy procedures, or in immunocompromised patients. The goal of prophylaxis is to prevent infection. For this to occur, there must be an adequate concentration of the antimicrobial agent in the tissue at the time of the incision. Historically, prophylaxis has consisted of intravenous administration of 1 gm. of cefazolin, 30 to 60 minutes prior to surgery. Cefazolin concentrations in the medial eminence of the first metatarsal were measured in patients undergoing bunionectomy procedures where pneumatic ankle tourniquets were used for hemostasis. The goal of this study was to determine if the current standards of prophylactic antibiotic administration provide adequate bone levels of cefazolin to effectively inhibit potential infection-causing pathogens.

Intravenous cefazolin in penetrating eye injuries. A swine model.

A swine model of penetrating ocular trauma was used to determine the delivery of systemically administered cefazolin to the vitreous cavity of traumatized and nontraumatized eyes. Thirty-one pigs received a scleral laceration to the right eye under anesthesia and then were given intravenous cefazolin every 8 hours. Seven pigs received nine doses at 17 mg/kg. Seven animals received three doses of 36 mg/kg, and six others received nine doses of this regimen. Six pigs received three doses of 79 mg/kg and five others received three doses of 190 mg/kg. Vitreous levels of cefazolin averaged 15.6 micrograms/mL in traumatized eyes but were less than 1 microgram/mL in control eyes of animals receiving three doses at 190 mg/kg (P < or = 0.025). Mean serum concentration in these animals was 49.3 micrograms/mL. Vitreous levels were less than 1 microgram/mL in traumatized and control eyes in animals given lower doses of cefazolin (range, 17-79 mg/kg) despite multiple treatments over 2 and 3 days. These data demonstrate that systemically delivered cefazolin achieves levels ten times the minimum inhibitory concentration for Staphylococcus epidermidis in injured eyes. Therapeutic intraocular levels can be obtained through intravenous dosing, provided that therapeutic serum concentrations are achieved.

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.

Serum cefazolin levels during spinal fusion: effect of blood loss and duration of surgery.

Perioperative cefazolin prophylaxis is commonly employed in posterior spinal fusion (PSF) procedures, which are often lengthy and involve significant blood loss. In this study, serum levels of prophylactically administered cefazolin were measured serially during spinal fusion procedures, and the possible relationship of antibiotic concentrations to blood loss and fluid therapy were examined. Serum antibiotic levels, measured at 30-min intervals, declined with a half-life of 90 min, similar to the previously reported experience with normal adult volunteers. There was no relationship between serum half-life and blood loss or fluid replacement. An explanation for these findings is offered, along with recommendations for dosing.

Evaluation of biodegradable cefazolin sodium microspheres for the prevention of infection in rabbits with experimental open tibial fractures stabilized with internal fixation.

Immediate internal fixation of severe open tibial fractures usually is contraindicated due to the high risk of infection. The objective of this study was to evaluate the efficacy of local antibiotic therapy with biodegradable poly-(DL-lactide-co-glycolide) cefazolin-loaded microspheres for the prevention of infection in experimental open fractures stabilized with internal fixation. Rabbits with experimental tibial fractures that were contaminated with Staphylococcus aureus were treated with local application of cefazolin microspheres, an equivalent local dose of free Ancef powder, or systemic Ancef therapy. The bones then were fixed with a four-hole plate, and the animals were observed for 8 weeks. Clinically, deep infection was present in 86% of control animals that received no antibiotics and in 60% of animals that received a 7 day course of systemic Ancef therapy. In contrast, no infections were noted among any of the surviving rabbits that received local therapy with either cefazolin microspheres or free Ancef powder. Significantly higher levels of serum cefazolin were measured at 1 h for animals treated with free Ancef powder (18.7 +/- 6.1 micrograms/ml) than for those treated with cefazolin microspheres (0.57 +/- 0.27 micrograms/ml). Follow-up studies are in progress to evaluate further the potential clinical benefits of local antibiotic therapy for the management of contaminated open fractures in humans.

Continuous infusion of cefazolin is superior to intermittent dosing in decreasing infection after hemorrhagic shock

Standard doses of antibiotic administered by intermittent infusions after hemorrhagic shock have decreased efficacy in combating infection. This study compared identical quantities of cefazolin administered after shock as intermittent doses or as continuous infusions in a subcutaneous abscess model. One hour after resuscitation from shock, rats were inoculated with 2 x 10(8) Staphylococcus aureus subcutaneously on the dorsum and divided into three groups: (1) control rats, which received no drug treatment; (2) rats in the intermittent group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, then every 8 hours for three doses, and (3) rats in the continuous infusion group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, followed by cefazolin, 90 or 180 mg/kg, intraperitoneally by continuous infusion more than 24 hours after inoculation. Seven days after the inoculation, abscess number, diameter, and weight were measured. Rats that received either dosage of cefazolin intermittently had the same abscess rate after shock as control rats. Rats that received a continuous infusion of cefazolin at either dose had 56% fewer abscesses than control rats. Abscess diameter and weight decreased with increasing quantities of cefazolin, and abscesses were always smaller in rats receiving the continuous infusion. There were no differences in peak subcutaneous cefazolin levels between the intermittent and continuous groups. Continuous infusion provided significantly more cefazolin to the tissue than an equivalent quantity of cefazolin delivered as intermittent doses. These data demonstrate that continuous infusion of cefazolin provided more antibiotic to the tissue and was superior to intermittent injection in reducing infection after hemorrhagic shock.

Endophthalmitis Therapy: Changing Antibiotic Sensitivity Patterns and Current Therapeutic Recommendations

To the Editor. —Martin and associates 1 reported vitreous cefazolin levels in a rabbit model of experimental endophthalmitis. These authors used heat-killed Staphylococcus epidermidis organisms to induce intraocular inflammation and then measured the penetration of systemically administered cefazolin. Meredith and associates 2 reported further rabbit model studies of S epidermidis endophthalmitis and observed no significant difference in inflammatory scores between the placebo-treated group and the group treated with 2.25 mg of intravitreal cefazolin. However, there were more eyes with clear media at the end of week 3 in the group treated with vitrectomy, 2.25 mg of intravitreal cefazolin, and either systemic or intravitreal corticosteroids. Although cefazolin does penetrate the eye from systemic administration and also may be used intravitreally, it is important to recognize that frequent resistance will occur among organisms commonly encountered in clinical endophthalmitis. Davis and associates 3 reported a series of cases of coagulase-negative staphylococci with a 19%

Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass

The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB). During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes. For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours. Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels. At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 ± 12 μg/L and 2.5 ± 0.6 μg/mL (mean ± SD), respectively. During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 μg/mL): average netilmicin levels were greater than MIC of sensitive bacteria (2 μg/mL) for 2 hours after antibiotic infusion. The netilmicin trough levels were 0.6 ± 0.5 μg/mL. Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin—elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg. The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively. Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P < 0.01) and the total body clearance greater (3.58 mL/kg/min, P < 0.01) than during surgery.

Vitreous Cefazolin Levels After Intravenous Injection

We devised a standardized rabbit model of intraocular inflammation using heat-killed Staphylococcus epidermidis as the inducing organism. We applied this model to study the effects of (1) inflammation, (2) repeated antibiotic doses, and (3) surgical status of the eye on cefazolin levels in the vitreous cavity after intravenous administration. Intravenous cefazolin sodium, 50 mg/kg, was administered every 8 hours for 48 hours. Eyes were harvested for assay of vitreous cavity antibiotic levels at various intervals from 1 to 49 hours. Drug levels were compared in inflamed and noninflamed eyes under both phakic and aphakic/vitrectomized conditions. At 1 hour, levels in phakic specimens were 3.0 mg/L in inflamed eyes vs undetectable in noninflamed eyes (P less than .01), but progressively increased to 10.6 mg/L at 49 hours (P less than .02) in inflamed eyes only. Levels in aphakic/vitrectomized eyes at 1 hour were 6.7 mg/L in inflamed eyes vs 4.2 mg/L in noninflamed eyes (P less than .1), but progressively increased to 24.9 mg/L at 49 hours (P less than .001) in inflamed eyes only. Levels at 49 hours in inflamed phakic and inflamed aphakic/vitrectomized eyes were well above the minimum inhibitory concentrations for organisms termed sensitive to cefazolin. We would conclude, therefore, that repeated doses of intravenous cefazolin may play an important adjunctive role in the treatment of endophthalmitis.

肝障害における各種抗生剤の体内分布に関する研究 第二編 実験的肝障害マウスにおける凍結下肝 Micro-Autoradiographyによる検討

In Part I of this study, the results obtained by bioassay (Okubo's band culture method)revealed that the carbenicillin (CBPC) and cefazolin (CEZ) levels were lower, while gentamicin (GM) levels were higher in experimentally damaged rat livers than in normal controls.In this Part of the study, the accumulation and localization of these antibi otics in damaged livers were directly observed by the micro-autoradiographical method.Mice, pretreated with a-naphthylisothiocyanate (ANIT) or carbon tetrachloride (CCl4)received 14C-benzylpenicillin (14C-PCG),14C-CEZ, or 3H-GM intramusclarly. Micro-autoradiography (MAR) was carried out on the liver tissues removed from the mice 30∼60 min. (60120 min, for GM) after injection of the labeled antibiotics.The results obtained were as follows:1) 14C-PCG: In the CCl4 damaged liver, the accumulation of grains produced by exposure to 14C-PCG was found to be delayed in the bile duct, but similar in the portal veins and in the hepatic cell regions in comparison with the controls. In the ANIT damaged liver, these grains were fewer in the bile ducts and hepatic cell regions, and more in the portal veins than in the normal liver.2) 14C-CEZ: In the CCl4 damaged liver, the grain accumulation was decreased in the bile ducts and in the hepatic cell regions, but increased in the portal veins. In the ANIT damaged liver every tissue site presented more grains in the experimentals than in the controls.3) 3H-GM: In the CCl4 damaged liver, abundant grains were found irregu larly accumulated in the hepatic cell regions around the central veins, where they never accumulate in a normal liver, and later on the grains were seen diffused throughout the whole of the fatty degenerated hepatic cell regions. Already during the early stage, more grains were also found in these bile ducts than in those of the normal Hiver. In the ANIT damaged liver, more grains were found in the Glisson's sheath regions, difusing into the hepatic cell regions, than in the control liver. Besides, it was note-worthy that the grains had accumulated in the spotty necrotic sites of the hepatic cell regions.Although all three of the antibiotics examined are those which are overwhelmingly excreted through the kidneys without being metabolized in the body, the above mentioned data show that GM completely differs in its kinetics in the damaged liver from CEZ or PCG, as GM is the only one which accumulates there.Although these findings require further study for interpretation in the clinical field, they may at least warn against the careless administration of aminoglicosides to liver damaged patients, even if not so imperatively as to patients with renal failure.

Therapeutic effects of cefotiam and cefazolin on experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice.

The efficacies of several dosage schedules, productive of plasma levels of cefotiam and cefazolin of short and long duration and starting at three levels of cefotiam and cefazolin of short and long duration and starting at three different times (3, 18, and 30h) after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. With each of the multiday regimens there was a large segment of the day when plasma levels fell below assayable concentrations. In all cases, cefotiam proved about eight times as active as cefazolin, indicating that the potent in vitro antibacterial activity of cefotiam was well reflected in the therapeutic effect in this model infection. As judged by the total dose administered, the regimen of cefotiam producing a low but sustained plasma level gave better therapeutic effects than that exhibiting a high but transient plasma level. The cefotiam levels in the plasma of mice that received the regimen effective when initiated at 18 h after infection were less than the expected levels in humans after intravenous infusion of the usual clinical dose.

Application of cephalosporins to obstetrics and gynecology: Transfer of cefazolin and cephalothin to uterine tissue

Antibiotics should be administered so as to maintain effective therapeutic levels in target organs. In routine clinical treatment, however, doses of antibiotics are determined on the basis of their achievable concentrations in blood. To determine the optimum doses of antibiotics against obstetric and gynecologic infections, the authors gave a single intravenous dose of 2 gm of cefazolin or cephalothin to 51 patients before hysterectomy and measured the levels of the antibiotics in uterine tissues and compared them with corresponding serum levels. The maximum tissue levels of cefazolin were generally about 6 to 7 times higher than those of cephalothin: In the perimetrium, levels were 154 μg/gm for cefazolin and 24.1 μg/gm for cephalothin; in the myometrium, 109.5 μg/gm for cefazolin, and 15.5 μg/gm for cephalothin; and in the endometrium, 98.9 μg/gm for cefazolin and 10.4 μg/gm for cephalothin. In the tissues, however, cephalothin reached peak levels more rapidly than cefazolin. Comparisons of the tissue levels and MIC of cefazolin and cephalothin revealed that cefazolin was maintained at over 12.5 μg/gm for at least 150 minutes in the perimetrium, myometrium, and endometrium, whereas cephalothin was maintained at these levels for 40 to 50 minutes only in the perimetrium and myometrium. The ratio of tissue levels to serum levels was 40–70 to 100 for cefazolin and about 30 or less to 100 for cephalothin.

Effect of protein binding on the penetration of nonmetabolized cephalosporins into atrial appendage and pericardial fluids in open-heart surgical patients.

At various times before surgery, 33 patients undergoing coronary artery bypass or cardiac valve replacement surgery received a single 2.0-g dose of either cefazolin or cephradine. Simultaneous single serum, atrial appendage, and pericardial fluid samples were obtained from the patients at various times and analyzed for drug content. Compared with cephradine, cefazolin yielded higher total serum, atrial appendage, and pericardial fluid levels. Unbound (free) levels of cephradine in serum and pericardial fluid were, however, higher than those of cefazolin. It remains uncertain whether the higher and more prolonged total levels of cefazolin in the right atrial appendage and in serum, or the higher free levels of cephradine in pericardial fluid and in serum, provide either one with a therapeutic advantage.

Serum Cefazolin Levels during Cardiopulmonary Bypass

This study was done to assess the adequacy of a regimen using cefazolin as a prophylactic antibiotic for patients undergoing open-heart operation. At the time of the preoperative medication, adult patients received 1 gm of cefazolin intramuscularly, and pediatric patients were given a dose of 20 mg per kilogram of body weight. Group I consisted of 10 adults undergoing a variety of cardiac procedures. The mean serum cefazolin level after institution of cardiopulmonary bypass was 27.36 μg/ml (range, 13.1 to 40.3 μg/ml). This level remained fairly stable throughout cardiopulmonary bypass. Group II consisted of 10 pediatric patients undergoing cardiac procedures for repair of a variety of congenital anomalies. The mean serum cefazolin level after institution of cardiopulmonary bypass was 20.01 μg/ml (range, 11.4 to 28.9 μg/ml) and remained stable for the duration of the procedure. In both groups perfusion pressure, urinary output, and body temperature did not seem to have any influence on these levels. It is concluded that the administration of one dose of cefazolin intramuscularly before operation results in an adequate and stable serum cefazolin level in patients undergoing cardiopulmonary bypass for up to three hours, possibly longer.

Double-blind comparison of cefazolin and cephalothin in open-heart surgery

Ninety-nine patients undergoing cardiac surgery were randomly assigned to treatment with cefazolin and cephalothin to compare the effectiveness of these cephalosporins in the prevention of postoperative infections. The incidence of infections was low with both antibiotics (cefazolin 2.1 percent, cephalothin 4.6 percent). Intraoperative serum cefazolin levels were more evenly distributed, whereas a wide dispersion of cephalothin levels was observed. There was no measurable antibiotic detected in cardiac tissue samples in the majority of the cases. Adverse reactions (skin rashes) occurred only in three patients, all receiving cephalothin. It is concluded that cefazolin is as safe and effective as cephalothin in the prevention of postoperative infection in patients undergoing open-heart surgery.