Comparative activity of cefoxitin, ampicillin/sulbactam, and imipenem against clinical isolates of Escherichia coli and Klebsiella pneumoniae

The in vitro activities of cefoxitin, ampicillin/sulbactam, and imipenem were determined by the standard twofold agar dilution method against 62 strains of Escherichia coli and 40 strains of Klebsiella pneumoniae isolated from patients in intensive care units. Judging from the concentrations required to inhibit at least 90% of the test isolates, imipenem (MIC90 less than or equal to 0.125 micrograms/ml) was markedly more active than cefoxitin (MIC90 = 4 micrograms/ml) and ampicillin/sulbactam (MIC90 = 32 micrograms/ml) against both bacterial genera. Cefoxitin, therefore, was more active than ampicillin/sulbactam against these organisms. Breakpoints specified in the prescribing information are less than or equal to 4 micrograms/ml for imipenem, less than or equal to 16 micrograms/ml for cefoxitin, and less than or equal to 8 micrograms/ml for ampicillin/sulbactam. At these breakpoints all organisms were susceptible to imipenem and cefoxitin, while 73% of E coli and 78% of K pneumoniae were susceptible to ampicillin/sulbactam. At recommended susceptible MIC breakpoints of the National Committee for Clinical Laboratory Standards (less than or equal to 4 micrograms/ml for imipenem, less than or equal to 8 micrograms/ml for cefoxitin, and less than or equal to 4 micrograms/ml for ampicillin/sulbactam) all the isolates tested were susceptible to imipenem, while 98% and 73% of the E coli isolates were susceptible to cefoxitin and ampicillin/sulbactam, respectively, and 100% and 78% of the K pneumoniae isolates were susceptible to cefoxitin and ampicillin/sulbactam, respectively. Approximately 14% of E coli and 17% of K pneumoniae isolates were resistant to ampicillin/sulbactam (MIC greater than or equal to 32/16 micrograms/ml).     

Ampicillin/sulbactam versus cefazolin or cefoxitin in the treatment of skin and skin-structure infections of bacterial etiology

This randomized, double-blind study compared 1 g of ampicillin plus 0.5 g of sulbactam with 0.5 g of cefazolin in the treatment of cellulitis and with 1 g of cefoxitin in other skin and skin-structure infections. Study drugs were administered intravenously every 6 hours to 58 hospitalized patients. Each indication was evaluated separately. In cellulitis, ampicillin/sulbactam and cefazolin produced clinical cure or improvement in 100% and 91.7% of patients, respectively; duration of hospitalization was 7.7 and 7.2 days. In other skin and skin-structure infections, results for ampicillin/sulbactam and cefoxitin, respectively, were clinical cure or improvement, 80% and 64.7%; treatment failures, 0% and 11.8%; bacterial eradication, 40% and 53%; and duration of hospitalization, 7.7 and 9.4 days. No unusual or unexpected adverse experiences related to any study drug occurred. One patient treated with ampicillin/sulbactam died of a pulmonary embolism, and 1 patient treated with cefoxitin was discontinued from the study following amputation of an infected foot. These events were not considered drug-related. The treatment groups showed no statistically significant differences in efficacy or safety.     

A comparison of ampicillin/sulbactam and cefoxitin in the treatment of bacterial skin and skin-structure infections

Seventy-six hospitalized patients with complicated skin/soft-tissue infections were enrolled in this randomized, prospective, third-party-blinded, comparative study of the effectiveness and safety of intravenous or intramuscular administration of ampicillin/sulbactam (1.0 to 2.0 g ampicillin plus 0.5 to 1.0 g sulbactam every 6 hours) and cefoxitin (1.0 to 2.0 g every 6 hours). Twenty-five of 36 ampicillin/sulbactam patients and 33 of 39 cefoxitin patients were evaluable. Clinical and bacteriologic effectiveness did not differ significantly between the two treatment groups (P = .674, P = .118, respectively); neither did duration of hospitalization (P = .894). Twenty-one (84%) ampicillin/sulbactam patients were cured, 2 (8%) were improved, and 2 (8%) were treatment failures. Twenty-eight (85%) cefoxitin patients were cured, 4 (12%) were improved, and 1 (3%) was a treatment failure. All primary pathogens were eradicated in 6 (24%) ampicillin/sulbactam patients; partial eradication occurred in 9 (36%). Primary pathogens were eradicated in 15 (47%) cefoxitin patients and partially eradicated in 8 (25%). Both treatments were well tolerated, with a small number of adverse reactions in each group. The overall incidence of adverse events was similar in the two groups.     

In vitro activities of antibacterial agents against clinical isolates of Escherichia coli and Klebsiella species from intensive care units

The susceptibility of 293 cultures of Escherichia coli and 160 cultures of Klebsiella species isolated consecutively from patients in intensive care units at 25 New York area hospitals to four antibiotic agents was determined. Susceptibility testing was performed with the reference agar dilution and broth microdilution procedures. At the minimum inhibitory concentration (MIC) breakpoints (specified in the prescribing information) of less than or equal to 4 micrograms/ml for imipenem, less than or equal to 16 micrograms/ml for cefoxitin, less than or equal to 8 micrograms/ml for ampicillin/sulbactam, and less than or equal to 64 micrograms/ml for ticarcillin/clavulanic acid, all isolates tested were susceptible to imipenem, 98% each of E coli and Klebsiella isolates were susceptible to cefoxitin, 75% and 83% to ampicillin/sulbactam and 96% and 92% to ticarcillin/clavulanic acid. At the recommended National Committee for Clinical Laboratory Standards MIC breakpoints (less than or equal to 4 micrograms/ml for imipenem, less than or equal to 8 micrograms/ml for cefoxitin, less than or equal to 8/4 micrograms/ml for ampicillin/sulbactam, and less than or equal to 16/2 micrograms/ml for ticarcillin/clavulanic acid) all isolates were susceptible to imipenem, 97% of E coli and 98% of Klebsiella isolates were susceptible to cefoxitin, 75% and 83% to ampicillin/sulbactam, and 86% each to ticarcillin/clavulanic acid. Of the 122 isolates with MICs greater than or equal to 128 micrograms/ml to ampicillin, only 19% were susceptible to ampicillin/sulbactam; and of the 150 isolates with MICs greater than 128 micrograms/ml to ticarcillin, 61% were susceptible to ticarcillin/clavulanic acid. The results suggest that, in the antibiotic combinations studied, high levels of penicillinases, capable of significantly affecting the utility of the enzyme inhibitors, are produced.     

A multicentre study to evaluate the effect of sulbactam/ampicillin combination on anaerobic micro-organisms

Ampicillin combined with the beta-lactamase inhibitor sulbactam was compared with ampicillin alone, cefoxitin and metronidazole against 569 clinical strains of anaerobic organisms. The strains included 289 species of Bacteroides, 160 strains of Clostridium and 120 strains of various species of Streptococcus/Peptostreptococus, Fusobacterium, Veillonella, Eubacterium, Bifidobacterium, Actinomyces and Propionibacterium. Sulbactam/ampicillin was as effective as cefoxitin and metronidazole against all anaerobic species tested, inhibiting more than 90% of strains at the breakpoints (16, 32 and 32 mg/l, respectively). Sulbactam/ampicillin was also significantly more active than ampicillin against strains of Bacteroides, the minimal inhibitory concentration being at least four-fold lower. In contrast, the activity of the combination did not differ from that of ampicillin alone against Fusobacterium species and Gram-positive rods and cocci.     

Susceptibilities of anaerobic gram-negative bacilli to thirteen antimicrobials and beta-lactamase inhibitor combinations.

Thirteen antimicrobial agents and beta-lactamase inhibitor combinations were tested simultaneously for their in-vitro activity against a range of anaerobic Gram-negative bacilli with a standard reference agar dilution method. Overall, metronidazole, imipenem, ampicillin/sulbactam, ticarcillin/clavulanic acid and cefoperazone/sulbactam, followed by clindamycin, cefoxitin, and piperacillin, had the greatest activity. Cefotetan, ceftizoxime, and cefoperazone were moderately active, while ampicillin and penicillin were least active. Metronidazole was the only drug active against all strains, but only one strain was resistant to imipenem. Resistance was highest among certain members of the Bacteroides fragilis group, but was observed also among numerous other Bacteroides species. beta-Lactamase was produced by 94% of strains in the B. fragilis group, and by 64% of strains overall. The activities of clindamycin and cefoxitin were compared with those in previous surveys since 1982 at our institution. No clear evidence of increasing resistance was demonstrated, but the data emphasized the significant effects resulting from variations in susceptibility testing.     

The antimicrobial susceptibility patterns of the Bacteroides fragilis group in the United States, 1987

A nationwide survey to monitor the susceptibility of the Bacteroides fragilis group, which began in 1981, was continued during 1987. In addition to the eleven drugs evaluated in 1986, sulbactam, a potent beta-lactamase inhibitor, was tested alone and in combination with ampicillin and cefoperazone. Imipenem, ampicillin/sulbactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid were the most active newer drugs tested, with less than 1% resistance rates. Chloramphenicol, metronidazole and clindamycin also had excellent activity with resistance rates of 0%, 0%, and 3% respectively. Resistance rates to cefoxitin remained stable at 8%. Ceftizoxime and cefotetan had resistance rates of 26% and 29%, respectively. Rates of resistance varied among different institutions and between the various species.     

The effects of clavulanic acid and sulbactam on beta-lactamase biosynthesis

Clavulanic acid and sulbactam were tested as inducers of beta-lactamase in 21 strains of Gram-negative bacteria. beta-Lactamase synthesis was inducible in all these strains, as demonstrated by the increased enzyme activities obtained when cells were grown in the presence of 10 mg/l of cefoxitin, the increase varying from 11- to 734-fold However, at the same concentration, neither inhibitor induced significant amounts of beta-lactamase, except in one strain of Providencia rettgeri, where both were potent inducers. When steps were taken to overcome the inhibitory effects of clavulanic acid and sulbactam, they were still found to be ineffective inducers. We conclude that, at therapeutic concentrations, clavulanic acid and sulbactam are generally poor inducers of beta-lactamase. Amoxycillin and ampicillin induced more beta-lactamase than the inhibitors, but were much less effective than cefoxitin, except for the strain of Prov. rettgeri.     

二氧化碳嗜纤维菌对β-内酰胺类抗生素的耐药性分析及基因型检测

目的 通过检测二氧化碳嗜纤维菌对β-内酰胺类抗生素的耐药性,了解其耐药机制.方法 收集3株二氧化碳嗜纤维菌,用纸片扩散法和Etest法检测二氧化碳嗜纤维菌对抗菌药物的敏感性,以Nitrocefin纸片法、三维法和PCR方法检测其β-内酰胺酶.结果 3株二氧化碳嗜纤维菌中有2株生痰二氧化碳嗜纤维菌,1株牙龈二氧化碳嗜纤维菌.3株菌对青霉素、氨苄西林、氨曲南、头孢噻肟、头孢他啶、头孢唑啉、头孢呋辛、头孢吡肟、头孢哌酮耐药,但对哌拉西林、亚胺培南、美罗培南、头孢西丁、氨苄西林/舒巴坦、头孢哌酮/舒巴坦、阿莫西林/克拉维酸、头孢他啶/克拉维酸、头孢噻肟/克拉维酸敏感.三维法试验结果显示3株二氧化碳嗜纤维菌所产的β-内酰胺酶能水解青霉素、氨苄西林、头孢噻肟、头孢他啶、头孢唑啉、头孢呋辛和头孢吡肟,但不能水解头孢西丁、亚胺培南和阿莫西林/克拉维酸.经PCR方法检测,3株二氧化碳嗜纤维菌的β-内酰胺酶和AmpC酶耐药基因均为阴性.结论 二氧化碳嗜纤维菌对常用抗菌药物尤其是β-内酰胺类抗生素均存在较高的耐药性,且其β-内酰胺酶可能存在新的基因型.     

Antimicrobial activity of ofloxacin and other agents against mycobacterial isolates from postoperative sternotomy wounds

In 1987 and 1988, 16 patients in a cardiothoracic hospital developed median sternotomy wound infections from Mycobacterium fortuitum or Mycobacterium chelonei (M fortuitum, 14 patients; M chelonei, two patients). For M fortuitum isolates, the minimum inhibitory concentration (MIC) (by agar dilution) of ofloxacin was 0.32 to 1.25 mg/L; of amikacin, 0.5 to 1 mg/L; of sulfadiazine, 16 to 256 mg/L; of imipenem, less than or equal to 2 to 4 mg/L; of cefoxitin, 4 to 16 mg/L; of ampicillin, 64 to greater than 256 mg/L; of cephapirin, 64 to 128 mg/L; of cefoperazone, greater than 256 mg/L; and of ceftazidime, greater than 256 mg/L. Addition of sulbactam to ampicillin and cefoperazone resulted in at least a four- to eight-fold reduction of their respective MICs. For M chelonei isolates, the MIC of ofloxacin was greater than 20 mg/L; of amikacin, 8 mg/L; of sulfadiazine, 64 mg/L; of imipenem, 8 mg/L; of cefoxitin, 16 mg/L; of ampicillin, 128 mg/L; of cephapirin, 128 mg/L; of cefoperazone, greater than 256 mg/L; and of ceftazidime, greater than 256 mg/L. Addition of sulbactam resulted in much smaller reductions of the MICs of ampicillin and cefoperazone. Synergism was noticed between ofloxacin and amikacin against M chelonei but not against M fortuitum. The results indicate that ofloxacin alone is as effective as the combination of ofloxacin and amikacin in treating M fortuitum, but not M chelonei, infection.     

基层医院铜绿假单胞菌医院感染现状及耐药性分析

目的探讨基层医院铜绿假单胞菌医院感染现状及其耐药性,为临床合理用药提供科学依据。方法对2008-2010年大英县人民医院感染性标本中分离的157株铜绿假单胞菌进行21种抗菌药物的体外药敏试验。结果 157株铜绿假单胞菌中痰液标本占60.5%,脓液及分泌物标本占17.2%,各种穿刺标本占12.1%。铜绿假单胞菌对常用抗菌药物的耐药率以亚胺培南最低,其他耐药率较低的还有左氧氟沙星、环丙沙星等,而耐药率〉90.0%的有氨苄青霉素/舒巴坦、氨苄青霉素、阿莫西林/克拉维酸、头孢西丁、加替沙星、复方新诺明。结论大英县人民医院铜绿假单胞菌的医院感染现状已相当严重,具有多药耐药性,须加强监测与控制。     

Purification and characterization of an imipenem hydrolysing metallo-beta-lactamase from Bacteroides fragilis.

An imipenem resistant beta-lactamase producing strain of Bacteroides fragilis was isolated from a clinical specimen. The specific activity of the unpurified beta-lactamase was 5.5 U/mg protein. The beta-lactamase was purified 60-fold by Q Sepharose, Sephacryl S-300 and Mono Q column passages. The strain was able to inactivate imipenem and cefoxitin in broth cultures. The enzyme hydrolysed imipenem more rapidly than ampicillin, benzylpenicillin, cephalothin and cefoxitin. The activity of the enzyme was Zn2+ dependent and was completely inhibited by EDTA. The inhibition was reversed by ZnSO4. Preincubation with the common beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam did not reduce the enzyme activity. The molecular weight was determined by sodium dodecyl sulfate gradient gel electrophoresis to be 31,000 Daltons and the isoelectric point was 4.5.     

Susceptibilities of beta-lactamase-positive and -negative strains of Campylobacter coli to beta-lactam agents.

The percentages of susceptibility of 28 strains of Campylobacter coli to beta-lactam agents were 96% for amoxicillin and ampicillin, 57% for ticarcillin, 4% for cefoxitin and cefuroxime, 61% for cefotaxime, and 11% for ceftazidime. None of the strains were susceptible to penicillin G, piperacillin, cefazolin, cephalothin, cefamandole, and cefoperazone. All strains were susceptible to imipenem and ciprofloxacin, and 21% were susceptible to erythromycin. A beta-lactamase was detected in 68% of the strains by cefinase disks and by the nitrocefin method. The beta-lactamase-positive strains were significantly less susceptible to amoxicillin, ampicillin, and ticarcillin than the beta-lactamase-negative strains (P < or = 0.003). Clavulanic acid (0.25 microgram/ml) but not sulbactam and tazobactam (2 micrograms/ml) lowered to susceptible levels the amoxicillin and ampicillin MICs of the only strain of C. coli resistant to amoxicillin, ampicillin, and ticarcillin.     

Pharmacokinetics of ampicillin and sulbactam in pediatric patients

Intravenous ampicillin-sulbactam is effective in the treatment of various infections in adults, but little is known about the pharmacokinetics (PK) of ampicillin-sulbactam in children. The objective of this study was to determine the PK of ampicillin and sulbactam in pediatric patients with intra-abdominal infection, skin and/or skin structure infection, or periorbital-preseptal and facial cellulitis. Intravenous ampicillin and sulbactam (2:1), 40 to 80 mg/kg of body weight, were given every 6 h for 2 to 6 days to 28 pediatric patients. The ages ranged from 1 to 6 years for 10 patients, 6.1 to 10 years for 9 patients, and 10.1 to 12 years for 9 patients. Multiple blood samples were obtained and analyzed for ampicillin and sulbactam in plasma and serum by high-performance liquid chromatography. The mean maximum concentration of drug in serum ranged from 177 to 200 micrograms/ml for ampicillin and 82 to 102 micrograms/ml for sulbactam in the three age groups. The mean total clearance, steady-state distribution volume, and half-life were 4.76 ml/min/kg, 0.32 liter/kg, and 0.77 h, respectively, for ampicillin and 4.95 ml/min/kg, 0.34 liter/kg, and 0.81 h, respectively, for sulbactam. Dose or gender did not affect the PK of ampicillin or sulbactam. The PK of ampicillin and sulbactam in these patients were comparable to those reported in adults. The combination was well tolerated in pediatric patients.     

泌尿系统感染病原菌分布及其耐药的调查

目的了解泌尿系感染病原菌分布及耐药性,为合理应用抗菌药物提供科学依据。方法通过细菌分离培养鉴定技术和K-B法,对尿液标本中分离出的病原菌进行鉴定和对临床常用抗生素进行了敏感试验。结果分离数在前9位的病原菌依次为大肠埃希菌,屎肠球菌(D群)、热带假丝酵母菌、光滑假丝酵母、粪肠球菌(D群)、白假丝酵母、肺炎克雷伯菌、表皮葡萄球菌、近平滑假丝酵母菌。大肠埃希菌对氨曲南、头孢吡肟、氨苄西林/舒巴坦、头孢噻肟、妥布霉素、奈替米星、头孢西丁、丁胺卡那、呋喃妥因、哌拉西林/他唑巴坦、舒普深较敏感(70.0%~100.0%),未发现耐万古霉素葡萄球菌属。结论大肠埃希菌为本地区泌尿系感染的主要病原菌,其次为屎肠球菌(D群),以往用于治疗泌尿系感染的常用药物如环丙沙星、庆大霉素、氨苄西林、左氧氟沙星等已产生较高的耐药性,因此,临床医师应结合药物敏感试验和特殊耐药菌株的报告,合理使用抗菌药物,减少、减缓耐药株的产生。     

Ampicillin/sulbactam in lower respiratory tract infections: a review.

The pathophysiology and microbiology of lower respiratory tract infections are outlined and diagnostic and therapeutic problems considered. The use of sulbactam/ampicillin in the treatment of these infections is evaluated. The two drugs have similar pharmacokinetic characteristics; predictable and dose-dependent peak serum concentrations of both agents are achieved after parenteral administration. More than 90% of strains of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella sp, Escherichia coli, and Acinetobacter sp were inhibited by ampicillin/sulbactam concentrations of 16/8 micrograms/ml. Serum concentrations of ampicillin and sulbactam were 18 to 28 micrograms/ml and 13 micrograms/ml, respectively, after intramuscular administration of 1 gm/0.5 gm of ampicillin/sulbactam and 58 micrograms/ml and 30 micrograms/ml, respectively, after intravenous administration of the same dose. Good distribution of ampicillin/sulbactam into lung tissue, sputum, and bronchial fluid has been demonstrated. In over 2,250 patients treated with ampicillin/sulbactam, the rate of discontinuance of treatment because of side effects was less than 1%. Satisfactory clinical and bacteriologic outcome has been reported in over 80% of patients treated with ampicillin/sulbactam. The cost of ampicillin/sulbactam treatment is generally lower than that of other comparable antibiotic regimens.     

Epigallocatechin gallate synergy with ampicillin/sulbactam against 28 clinical isolates of methicillin-resistant Staphylococcus aureus

Compared with ampicillin, oxacillin, cefmetazole and imipenem, the combination of ampicillin and sulbactam at a constant ratio of 2:1 showed the greatest effect against 28 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), but MICs of ampicillin/sulbactam were still above the resistance breakpoint. When ampicillin/sulbactam was further combined with epigallocatechin gallate (EGCg, a main constituent of tea catechins), the MIC90 of ampicillin/ sulbactam was reduced to 4 mg/L, the susceptibility breakpoint. The fractional inhibitory concentration indices were between 0.19 and 0.56 in combination with 6.25 and 25 mg/L EGCg, respectively, indicating that ampicillin/sulbactam and EGCg combination may be effective against MRSA infections.     

Sulbactam/ampicillin: effects on glucose metabolism in diabetics with soft tissue infection

Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study.     

Clinical results with sulbactam/ampicillin in a multicenter study of 425 patients

In an open, non-comparative multicenter study, efficacy and toleration of sulbactam/ampicillin for therapy of various infections were investigated. 42 centers in the Federal Republic of Germany and West-Berlin participated in this study. In total, 425 patients were included, 112 of whom suffered from renal/urinary tract infections, 103 from respiratory tract infections, 84 from intraabdominal infections, and 73 from skin/soft tissue infections. Moreover, 43 female patients had gynecological infections. More than 95% of the patients received three daily dosages of 3 g sulbactam/ampicillin via intravenous short-infusion. Mean duration of therapy was 7.3 days. In 280 patients, in total, pathogens were initially identified, among them were 87 patients with mixed infections. At study onset, 393 pathogens were identified, after completion of the trial 63 germs could still be made evident. In 234 cases (= 83.6%) pathogens were eradicated by therapy, in 19 patients superinfection occurred, and in 27 patients pathogenic organisms persisted. 419 patients were included into evaluation of clinical efficacy of sulbactam/ampicillin therapy. In 391 cases (= 93.3%) therapy was successful with 293 patients cured and 98 improved. Therapy failed in 28 patients (= 6.7%) which, in 23 cases, led to discontinuation of treatment. Sulbactam/ampicillin was well tolerated. In total, 55 adverse drug reactions were observed, 22 of which were exanthemas (= 5.2% of all patients). In seven patients (= 1.6%) therapy had to be discontinued due to adverse events. The combination of sulbactam, a beta-lactamase inhibitor, with the reliable antibiotic agent ampicillin has proved to be successful in therapy of infections of different localizations with excellent toleration.     

Pharmacokinetics of ampicillin and sulbactam in patients undergoing heart surgery.

The pharmacokinetics of ampicillin and sulbactam, a new beta-lactamase inhibitor, were investigated in 16 patients undergoing prosthetic cardiac valve insertion. The combination of 2 g of ampicillin and 1 g of sulbactam was administered as perioperative prophylaxis intravenously over 3 to 6 days. Several serum pharmacokinetic parameters were similar for the two drugs after three intravenous doses were given to patients following surgery. The half-lives of elimination of ampicillin and sulbactam were 79 +/- 4.9 and 88 +/- 5.9 min, the volumes of distribution were 15.6 +/- 1.4 and 17.7 +/- 1.2 liters/70 kg, and the total plasma clearances were 144.4 +/- 14.5 and 147.2 +/- 14.5 ml/min, respectively. The peak concentrations of ampicillin and sulbactam in serum were calculated to be 134.3 +/- 1.3 and 58.3 +/- 1.2 micrograms/ml, respectively. Ampicillin and sulbactam rapidly penetrated from the blood into various tissues collected during heart surgery, such as sternum, pericardium, myocardium, and endocardium. The concentrations of ampicillin in tissue ranged from 17.8 +/- 9.9 to 50 +/- 29.5 micrograms/g, and those of sulbactam in tissue ranged from 8.8 +/- 6.2 to 19.6 +/- 10.1 micrograms/g. The concentrations of ampicillin and sulbactam in serum and tissue also apparently exceeded the MICs against most beta-lactamase-producing bacteria usually involved in postoperative wound infections and prosthetic valve endocarditis. The ratio of the two compounds was approximately 2:1 in serum and in the various tissues affected by the operation. The pharmacokinetics of ampicillin and sulbactam in serum and investigated tissues suggest that the combination of the two beta-lactams will be effective in the perioperative prophylaxis of patients undergoing heart surgery.