Ampicillin/sulbactam and cefoxitin in the treatment of cutaneous and other soft-tissue abscesses in patients with or without histories of injection drug abuse.

A randomized, double-blind trial compared the clinical and bacteriologic efficacy of ampicillin/sulbactam (2 g/1 g) and cefoxitin (2 g) administered intravenously every 6 h to patients with (n=49) or without (n=47) histories of injection drug abuse who presented with cutaneous or other soft-tissue infections. Cure or improvement occurred in 89.8% of ampicillin/sulbactam-treated patients, compared with 93.6% of cefoxitin-treated patients. The median time to resolution of all symptoms was 10.5 days with ampicillin/sulbactam treatment and 15.5 days with cefoxitin treatment. Mixed aerobic-anaerobic infection was encountered frequently in both treatment groups. A significantly higher percentage of Streptococcus species was found in the major abscesses of the patients with histories of injection drug abuse, compared with those without such histories (37% vs. 19%, respectively; P=.0009). Overall, ampicillin/sulbactam eradicated pathogens from the major abscesses in 100% of patients, whereas the eradication rate with cefoxitin was 97.9%. The 2 drugs were well tolerated. Ampicillin/sulbactam and cefoxitin were equally effective for the empirical treatment of cutaneous or other soft-tissue infections in injection drug abusers and patients who did not inject drugs.     

Contribution of animal models in the search for effective therapy for endocarditis due to enterococci with high-level resistance to gentamicin.

Earlier studies suggest that ampicillin and amoxicillin are more effective than other beta-lactam agents in killing enterococci, although beta-lactam agents are slowly and incompletely bactericidal against most strains of Enterococcus faecalis. We previously showed that continuous infusion of ampicillin is more effective than intermittent administration in decreasing the number of enterococci in valvular vegetations of rats with catheter-induced endocarditis that are treated for 5 days. In this model, we found ampicillin plus sulbactam more effective than ampicillin alone against a beta-lactamase-producing enterococcal strain with high-level resistance to gentamicin. Daptomycin therapy produced results approximately equal to those of ampicillin plus sulbactam. Vancomycin and teicoplanin given for 5 days at doses producing equivalent serum levels had approximately equal efficacy. However, 10-day therapy with low-dose teicoplanin was considerably more effective than similar treatment with vancomycin. High-dose teicoplanin for 5 days produced sterile valves in 82% of the animals studied.     

Concentrations of ampicillin and sulbactam in serum and tissues of patients undergoing ENT surgery

Summary 2 g ampicillin and 1 g sulbactam were given by infusion to 24 patients who were to be operated on in the ENT region. About 1 hour later during the operation samples of serum and of various tissues were taken and analysed for ampicillin and sulbactam. The mean serum concentrations of ampicillin and sulbactam were 59.2 mg/l and 31.6 mg/l, respectively. At the same time the concentrations of the two drugs were usually lower in the tissues than in serum. About 1 hour after the infusion the mean tissue concentration of ampicillin was 33.5 mg/kg and of sulbactam 19.5 mg/kg. The results show that ampicillin and sulbactam penetrate within an hour into the different tissues affected by the operation and maintain about the same ratio as in serum (2:1). The concentrations of ampicillin and sulbactam measured in the different compartments are capable of inhibiting the bacteria most frequently involved in ENT infections. These measurements unequivocally support the use of the ampicillin/sulbactam combination in the treatment and perioperative prophylaxis of bacterial infections of the ENT tract.

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Konzentrationen von Ampicillin und Sulbactam in Serum sowie Geweben von Patienten der HNO-Chirurgie

Zusammenfassung Die Konzentrationen von Ampicillin und Sulbactam wurden etwa 1 Stunde nach Infusion im Serum und verschiedenen Geweben bei 24 Patienten, die sich einem chirurgischen Eingriff im HNO-Bereich unterzogen, bestimmt. Den Patienten wurden vor der Operation 2 g Ampicillin und 1 g Sulbactam infundiert. Die Mittelwerte der Konzentrationen von Ampicillin und Sulbactam betrugen im Serum der Patienten 59,2 mg/l bzw. 31,6 mg/l. Die Konzentrationen der beiden Arzneistoffe waren zur gleichen Zeit in den verschiedenen Geweben in der Regel geringer als im Serum. Die Mittelwerte der Gewebe-Konzentrationen waren etwa 1 Stunde nach Infusion für Ampicillin 33.5 mg/kg und für Sulbactam 19.5 mg/kg. Die Ergebnisse zeigen, daß Ampicillin und Sulbactam bereits innerhalb einer Stunde in die verschiedenen von der Operation betroffenen Gewebe der Patienten penetrieren und in einer ähnlichen Relation (2:1) wie im Serum vorliegen. Die in den unterschiedlichen Kompartimenten gemessenen Konzentrationen von Ampicillin und Sulbactam hemmen die an HNO-Infektionen vorwiegend beteiligten Bakterien. Aufgrund dieser pharmakokinetischen Daten gilt die Kombination Ampicillin/Sulbactam als geeignet für die Behandlung und perioperative Prophylaxe bakterieller Infekte des HNO-Bereiches.

     

Pharmacokinetics of ampicillin, sulbactam and cefotiam in patients undergoing orthopedic surgery

Summary As perioperative prophylaxis for major orthopedic operations 81 patients were given the fixed combination of ampicillin (1 g)/ sulbactam (0.5 g) or cefotiam (2 g) as short infusions. The three -lactams were rapidly distributed into the different tissues and their pharmacokinetic profiles were found to be very similar. It was noteworthy that ampicillin, sulbactam and cefotiam penetrated within minutes, not only into skin, fat and muscles, but also into bone. Thus 0.25 h after starting the infusion the following mean concentrations were measured in bone: 21.8±10.5 mg/kg ampicillin, 4.9±2.2 mg/kg sulbactam and 19.4±10.6 mg/kg cefotiam. For a period of at least 2 h the concentrations measured in serum and in the different tissues affected by the operation (skin, fat, muscle, bone) were above the MICs for pathogens which are involved in postoperative wound infections. On the basis of pharmacokinetic data, ampicillin/sulbactam and cefotiam seem about equally suitable for perioperative prophylaxis in major orthopedic operations.     

Concentrations of sulbactam/ampicillin in serum and lung tissue

Summary The penetration of sulbactam plus ampicillin into lung tissue was studied in 15 patients undergoing thoracic surgery for pneumonectomy after the administration of 1 g of sulbactam plus 2 g of ampicillin as a 15 min intravenous short infusion. Ampicillin serum concentrations declined from 40.8 mg/l at 1 h to 18.8 mg/l 2–4 h after administration. Concomitant serum concentrations of sulbactam were 25.5 mg/l and 11.8 mg/l, respectively. In lung tissue, peak ampicillin concentrations of 35.6 mg/kg were reached 1.5 h after administration declining slowly to 26.8 mg/kg after 2–4 h. The respective sulbactam concentrations were 8.6 and 5.5 mg/kg. In our study sufficient sulbactam and ampicillin levels active against important pathogenic organisms causing community-and hospital-acquired respiratory tract infections have been achieved in lung tissue, suggesting that the combination sulbactam/ampicillin is suited for the treatment of most community- and hospital-acquired respiratory tract infections as well as for chemoprophylaxis and treatment of postoperative lung infections after thoracic surgery.

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Konzentrationen von Sulbactam/Ampicillin in Serum und Lungengewebe

Zusammenfassung Die Antibiotika-Wirkstoffkonzentrationen von Sulbactam/Ampicillin in Lungengewebe wurden bei 15 lungenchirurgischen Patienten untersucht, denen präoperativ vor Pneumonektomie eine i. v. Kurzinfusion von 1 g Sulbactam plus 2 g Ampicillin verabreicht wurde. Die Serumkonzentration von Ampicillin betrug 1 Stunde nach Antibiotikagabe 40,8 mg/l und fiel nach 2–4 Stunden auf 18,8 mg/l ab. Die entsprechenden Serumkonzentrationen von Sulbactam betrugen 25,5 mg/l nach 1 Stunde und 11,8 mg/l nach 2–4 Stunden. Der Spitzenspiegel von Ampicillin in Lungengewebe wurde nach 1,5 Stunden bestimmt und betrug 35,6 mg/kg; nach 2–4 Stunden wurden noch 26,8 mg/kg gemessen. Die Lungengewebespiegel von Sulbactam sanken von 8,6 mg/kg nach 1 Stunde auf 5,5 mg/kg nach 2–4 Stunden. Die gemessenen Wirkstoffkonzentrationen von Sulbactam und Ampicillin waren ausreichend, um die wichtigsten Erreger ambulant- und krankenhaus-erworbener Atemwegsinfektionen zu hemmen. Die Kombination Sulbactam/Ampicillin ist daher geeignet für die Behandlung ambulanter und nosokomialer Atemwegsinfektionen sowie für die Antibiotikaprophylaxe und Behandlung von postoperativen Lungeninfektionen nach thoraxchirurgischen Eingriffen.

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Supported by Pfizer GmbH, Karlsruhe, Germany     

In vitro activity of sulbactam plus ampicillin against hospital isolates of coagulase-negative staphylococci and acinetobacter species

Summary The antimicrobial susceptibility of 54 recent clinical isolates of coagulase-negative slime- and non-slime-producing staphylococci and 52Acinetobacter spp. to sulbactam, ampicillin and the combination of both drugs with a 1:1 ratio was studied by means of an agar dilution test. The coagulase-negative staphylococci showed resistance against sulbactam alone, whereas ampicillin as a single agent was nearly as active as sulbactam plus ampicillin (mode of MIC and MBC 0.03 and 4 mg/l vs. 1 mg/l; geometric mean of MIC and MBC 0.38 and 0.56 vs. 0.26 and 0.38 mg/l, respectively). Among slime-producing or non-slime-producing strains, there was no difference in the susceptibility against ampicillin alone compared to the sulbactam/ampicillin combination, with the exception of the higher MBC (mode: 4 mg/l) for slime-producing strains. Both ampicillin and the sulbactam/ampicillin combination were more active against non-slime-producing than slime-producing strains with modes of MIC and MBC of 0.03 vs. 1 or 4 mg/l.Acinetobacter spp. were susceptible to sulbactam alone (mode of MIC and MBC 1 mg/l; geometric mean of MIC and MBC 1.51 and 2.98, respectively), but resistant to ampicillin. However, the sulbactam/ampicillin combination was highly active againstAcinetobacter spp. (mode of MIC and MBC 0.5 and 2 mg/l; geometric mean of MIC and MBC 0.74 and 2.08 mg/l, respectively).

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In vitro-Aktivität von Sulbactam plus Ampicillin gegen klinische Isolate von koagulase-negativen Staphylokokken und Acinetobacter-Spezies

Zusammenfassung Bei klinischen Isolaten von 54 koagulase-negativen schleimbildenden und nicht-schleimbildenden Staphylokokken und 52 Acinetobacter-Spezies wurde im Agardilutionstest das Resistenzverhalten gegenüber Sulbactam, Ampicillin und der 1:1-Kombination aus beiden Substanzen untersucht. Die koagulase-negativen Staphylokokken erwiesen sich als sulbactam-resistent, jedoch gleichsam ampicillin- wie sulbactam/ampicillin-empfindlich (MHK- bzw. MBK-Modalwert Ampicillin: 0,03 bzw. 4 mg/l; Sulbactam/Ampicillin: jeweils 1 mg/l; geometrischer MHK- bzw. MBK-Mittelwert Ampicillin: 0,38 bzw. 0,56 mg/l, Sulbactam/Ampicillin: 0,26 bzw. 0,38 mg/l). In der Empfindlichkeit schleimbildender oder nicht-schleimbildender Stämme bestand gegen Ampicillin im Vergleich zur Kombination kein Unterschied; eine Ausnahme hiervon machte nur die höhere Ampicillin-MBK (Modalwert: 4 mg/l) gegen die schleimbildenen Stämme. Ampicillin sowie Sulbactam/Ampicillin zeigten größere Wirksamkeit gegen nichtschleimbildende als gegen schleimbildende Stämme mit MHK- bzw. MBK-Modalwerten von 0,03 vs 1 mg/l. Acinetobacter-Spezies waren sulbactam-empfindlich (MHK- bzw. MBK-Modalwert 1 mg/l; geometrischer MHK- bzw. MBK-Mittelwert 1,51 bzw. 2,98 mg/l), jedoch ampicillin-resistent. Die Kombination Sulbactam/Ampicillin dagegen zeigte eine sehr gute Wirksamkeit gegen die Keime aus der Acinetobacter-Gruppe (MHK-bzw. MBK-Modalwert 0,5 bzw. 2 mg/l; geometrischer MHK- bzw. MBK-Mittelwert 0,74 bzw. 2,08 mg/l).

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Supported by Pfizer G.m.b.H. Karlsruhe.     

Clindamycin treatment of experimental chronic osteomyelitis due to Staphylococcus aureus

Clindamycin was used alone for treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 30 mg/kg of body weight three times a day for 14 days was ineffective in sterilizing infected rabbit bones. In contrast, when given for 28 days, clindamycin sterilized the infected bones of 16 (84%) of 19 rabbits treated. Only one of 14 isolates of S. aureus from rabbits treated for two weeks developed resistance to clindamycin (minimal inhibitory concentration, greater than 100 micrograms/ml); none of three isolates from rabbits in which treatment failed in the four-week treatment group showed resistance to clindamycin. The results of four weeks of treatment with clindamycin for chronic experimental staphylococcal osteomyelitis were significantly better than those obtained with any other single agent used in prior studies and were generally as good as those with combination therapy that included rifampin.     

Biliary infection and bacteremia caused by beta-lactamase-positive, ampicillin-resistant Haemophilus influenzae in a diabetic patient

We report the case of a 73-year-old female patient with diabetic nephropathy and cholelithiasis. She was admitted to our hospital with right upper abdominal pain, nausea, and vomiting. The patient had visited an outpatient clinic with the same complaints 2 days earlier, and had been prescribed antibiotics empirically (two doses ofloxacin orally). Blood cultures taken before the start of antibiotic treatment in our hospital were negative. The patient was treated with parenteral ampicillin/sulbactam + ciprofloxacin empirically. The empiric antibiotic treatment was discontinued after 7 days. Elective cholecystectomy was performed after her general condition improved. An aerobic chocolate agar culture of the cholecystectomy material yielded Haemophilus influenzae type b. On postoperative day 3 the patient developed fever again. The fluids collected after cholecystectomy were evaluated microbiologically. H. influenzae type b was isolated from the samples and blood cultures. The patient was diagnosed with H. influenzae cholecystitis, and recovered after 10-day treatment with ampicillin/sulbactam + ciprofloxacin. The findings are discussed together with references for differential diagnosis. H. influenzae cholecystitis due to cholelithiasis, although rare, should be considered in elderly patients with a history of chronic diseases such as diabetes mellitus or nephropathy.     

小儿急性细菌性痢疾的病原菌分布特征及耐药性分析

目的探究小儿急性细菌性痢疾的病原菌分布特征并对其耐药情况进行分析,为小儿急性细菌性痢疾的治疗提供参考依据。方法选取2016年1月—2019年7月亳州市人民医院确诊为小儿急性细菌性痢疾的80例患儿作为研究对象,对其临床资料如体温、腹泻次数、粪便状态等及实验检查如粪便病原菌培养和药物敏感试验结果进行统计分析。结果小儿急性细菌性痢疾病原菌以福氏志贺菌(S.flexneri)检出率最高、宋内氏志贺菌(S.sonnei)其次、鲍氏志贺菌(S.boydii)最低;3群志贺菌同时耐药的抗生素有11种,耐药率较高的抗生素有氨苄西林、氨苄西林舒巴坦、环丙沙星、庆大霉素;敏感率较高的有厄他培南、亚胺培南、哌拉西林他唑巴坦、头孢他啶;3群志贺菌对哌拉西林他唑巴坦敏感率均为100%;各群志贺菌耐药情况在各年度大致相同,氨苄西林舒巴坦、庆大霉素与妥布霉素耐药例数逐年递增,S.sonnei和S.boydii耐药抗生素相对S.flexneri较少。结论小儿急性细菌性痢疾病原菌耐药情况不容乐观,要加强对小儿急性细菌性痢疾的病原菌培养及耐药监测,合理使用抗生素,控制病原菌耐药演变与流行。     

头孢哌酮/舒巴坦对老年医院获得性肺炎的疗效分析

目的 探讨头孢哌酮/舒巴坦对老年医院获得性肺炎(HAP)治疗效果.方法 对我院收治的98例老年医院获得性肺炎患者随机分为实验组及对照组,实验组患者用头孢哌酮/舒巴坦进行治疗,对照组患者采用头孢哌酮进行治疗,治疗后对两组患者疗效以及细菌清除率进行比较.结果 实验组患者的治疗效果以及致病菌的清除率明显优于对照组(P＜0.05).结论 头孢哌酮/舒巴坦对老年医院获得性肺炎具有良好的治疗效果,致病菌对其耐药性低.     

A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot

The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies. Among 12 studies comparing different antibiotic regimens in the management of skin and soft-tissue infection, none reported a better response with any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft-tissue infection or osteomyelitis. In one non-randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors. Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte-colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foot.     

Infectious complications after 809 biliary tract operations and results of a prospective randomized single-blind study comparing cefoxitin versus ampicillin plus an inhibitor of β-lactamases

Summary A retrospective analysis of 809 biliary tract operations revealed postoperative wound infections in 13.4% of 278 patients with bactericholia, compared to 6.9% in patients without bactericholia. More than one third of isolated bacteria were resistant to ampicillin. This was the basis to conduct a prospective randomized single-blind study to compare the efficacy of ampicillin in combination with the beta-lactamase-inhibitor sulbactam with cefoxitin as perioperative prophylaxis in elective biliary surgery. Patients received a single dose of either 2 g ampicillin plus 1 g sulbactam or 2 g cefoxitin as intravenous short-infusion approximately 30 min prior to skin incision. Both groups were comparable concerning demographic and nosographic data. 80 of 83 patients were evaluable for efficacy; 39 received ampicillin/sulbactam and 41 cefoxitin. In the cefoxitin group two wound infections were observed. In the ampicillin/sulbactam group one patient developed post-operative temperatures of >39.0° C, which was regarded as a wound-related infectious complication. In addition, there occurred five urinary tract infections (cefoxitin: 3; ampicillin/sulbactam: 2) but no pulmonary infection. In conclusion, no significant difference between the two groups could be shown. Both regimens were well tolerated with no significant differences between treatment groups. The combination of ampicillin with the -lactamase-inhibitor sulbactam can be regarded as safe and as effective compared to cefoxitin for single-dose prophylaxis of post-operative infections after biliary tract operations.

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Infektionsbedingte Komplikationen nach 809 Gallenwegsoperationen und Ergebnisse einer prospektiven, randomisierten einfachblinden Vergleichsstudie zwischen Cefoxitin und Ampicillin plus einem -Lactamase-Inhibitor

Zusammenfassung Eine retrospektive Analyse von 809 Gallenwegsoperationen zeigte bei 278 Patienten mit Bakteriobilie (34,4%) eine Inzidenz postoperativer Wundinfektionen in Höhe von 13,4% gegenüber 6,9% bei den Patienten ohne Bakteriobilie. Mehr als ein Drittel der isolierten Bakterien war resistent gegenüber Ampicillin. Hiervon ausgehend wurde eine prospektive randomisierte einfachblinde Studie zur Wirksamkeit der Kombination von Ampicillin mit dem -Lactamase-Inhibitor Sulbactam im Vergleich zu Cefoxitin im Rahmen der perioperativen Prophylaxe bei gallenchirurgischen Elektiveingriffen durchgeführt. Es wurden entweder 2 g Ampicillin plus 1 g Sulbactam oder 2 g Cefoxitin jeweils als Einmaldosis in Form einer i.v.-Kurzinfusion ca. 30 min vor Hautschnitt verabreicht. Die Behandlungsgruppen waren hinsichtlich der demographischen und nosographischen Daten vergleichbar. 80 von 83 Patienten waren auswertbar, hiervon erhielten 39 Ampicillin/Sulbactam und 41 Cefoxitin. In der Cefoxitin-Gruppe traten zwei Wundinfektionen auf, in der AMP/SBT-Gruppe entwickelte ein Patient postoperative Temperaturen >39,0° C, was als wundbezogene Komplikation angesehen wurde. Weiterhin traten fünf Harnwegsinfektionen (Cefoxitin: 3; Ampicillin/Sulbactam: 2), jedoch keine pulmonale Infektion auf. Insgesamt zeigte sich kein signifikanter Unterschied zwischen den Behandlungsgruppen. Die Verträglichkeit war in beiden Gruppen gut, signifikante Unterschiede wurden nicht beobachtet. Die Kombination von Ampicillin mit dem -Lactamase-Inhibitor Sulbactam ist im Vergleich zu Cefoxitin als genauso sicher und effektiv in der Eindosis-Prophylaxe postoperativer Infektionen nach Gallenwegsoperationen anzusehen.

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Supported by Pfizer GmbH, Karlsruhe, FR Germany     

Alterations in the human oropharyngeal microflora related to therapy with aztreonam, moxalactam and ampicillin plus sulbactam

33 patients undergoing colorectal surgery were treated prophylactically with aztreonam (19 patients), moxalactam (10 patients) and ampicillin plus sulbactam (4 patients). The effect on the normal oropharyngeal microflora and new colonization of oropharynx were studied during and after the treatment. Aztreonam had minor effect on the normal flora but induced colonization with staphylococci. Moxalactam suppressed gram-negative aerobic and anaerobic bacteria and promoted colonization with Candida albicans. Ampicillin plus sulbactam had marked effect on the normal flora and suppressed aerobic as well as anaerobic bacteria. New colonization with enteric gram-negative rods or fungi was observed in all patients.     

Sulbactam/ampicillin compared with cefoxitin for chemoprophylaxis in elective colorectal surgery

In a prospective, randomized, comparative study, patients undergoing elective major colorectal surgery received four six-hour doses of either sulbactam (a β-lactamase inhibitor) with ampicillin (1 gm with 1 gm), or cefoxitin (2 gm) commencing at induction of anesthesia. The groups were well matched for age, sex, diagnosis, and surgical procedures. Three patients in the sulbactam group (N=44), and four in the cefoxitin group (N=48) developed significant would sepsis. Minor wound sepsis occurred in an additional four sulbactam patients, and in five cefoxitin patients. There was no difference between the groups in deep sepsis or anastomotic leak rates (sulbactam, four patients; cefoxitin, seven patients). No serious side effects were recorded in either group. These results suggest that sulbactam combined with ampicillin provides a safe, effective alternative to cefoxitin for prophylaxis in colorectal surgery.     

Moxifloxacin vs Ampicillin/Sulbactam in Aspiration Pneumonia and Primary Lung Abscess

Abstract Background: Aspiration pneumonia (AP) and primary lung abscess (PLA), are diseases following aspiration of infectious material from the oropharynx or stomach. An antibiotic therapy, also covering anaerobic pathogens, is the treatment of choice. In this study we compared moxifloxacin (MXF) and ampicillin/sulbactam (AMP/SUL) concerning efficacy and safety in the treatment of AP and PLA. Methods: Patients with pulmonary infections following aspiration were included in a prospective, open-label, randomized, multicenter trial. Sequential antibiotic therapy with MXF or AMP/SUL was administered until complete radiologic and clinical resolution. Results: A total of 139 patients with AP and PLA were included, 96 were evaluable for efficacy (EE, 48 patients in each treatment group). The overall clinical response rates in both groups were numerically identical (66.7%). MXF and AMP/SUL were both well tolerated, even after long-term administration [median duration of treatment (range) in days MXF versus AMP/SUL: AP 11 (4–45) vs 9 (3–25), PLA 30.5 (7–158) vs 35 (6–90)]. Conclusion: In the treatment of aspiration-associated pulmonary infections moxifloxacin appears to be clinically as effective and as safe as ampicillin/sulbactam; but, however, having the additional benefit of a more convenient (400 mg qd) treatment.     

In vitro activity of ampicillin plus sulbactam against anaerobes compared to ampicillin and cefoxitin

Summary The antimicrobial susceptibility of 195 recent clinical isolates of anaerobic bacteria was studied to ampicillin alone, ampicillin +1 mg/l sulbactam, ampicillin +5 mg/l sulbactam, and cefoxitin by means of agar dilution tests. The ampicillin-sulbactam combinations were the most effective drugs against species of theBacteroides fragilis group, the MIC₉₀ of ampicillin +5 mg/l sulbactam forB. fragilis being <1 mg/l, compared to 256 mg/l of ampicillin, 4 mg/l of ampicillin +1 mg/l sulbactam, and 8 mg/l of cefoxitin. No significant difference between ampicillin alone and in combination with sulbactam was observed against gram-positive anaerobic rods,Peptococcus spp. andPeptostreptococcus spp. with MIC's <2 mg/l.

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In vitro-Aktivität von Ampicillin plus Sulbactam gegen Anaerobier im Vergleich zu Ampicillin und Cefoxitin

Zusammenfassung Bei 195 Stämmen strikt anaerober Bakterien aus klinischen Isolaten wurde im Agardiffusionstest das Resistenzverhalten gegenüber Ampicillin alleine, Ampicillin +1 mg/l Sulbactam, Ampicillin +5 mg/l Sulbactam und Cefoxitin untersucht. Die Kombinationen aus Ampicillin und Sulbactam zeigten eine sehr gute Wirkung gegenüber Spezies aus derBacteroides fragilis-Gruppe, so betrug gegenüberB. fragilis (s. s.) die MHK₉₀ für Ampicillin +5 mg/l Sulbactam <1 mg/l, verglichen mit 256 mg/l für Ampicillin alleine, 4 mg/l für Ampicillin +1 mg/l Sulbactam und 8 mg/l für Cefoxitin. Bei grampositiven anaeroben Stäbchenbakterien,Peptococcus spp. undPeptostreptococcus spp. waren im Vergleich zwischen Ampicillin alleine und in Kombinationen mit Sulbactam keine signifikanten Unterschiede festzustellen. Die MHK₉₀ betrug bei diesen Keimen weniger als 2 mg/l.

     

Ampicillin/sulbactam in elderly patients with community-acquired pneumonia

Purpose

Age-related physiological changes affect body systems, altering pharmacokinetics, which may potentiate or alter the effects of drugs. The aim of this study was to assess the influence of age on the steady-state pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam in the population of elderly patients (age ≥65 years) with community-acquired pneumonia (CAP).

Patients and methods

The pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam were determined at steady state in a total of 13 elderly patients with CAP following the administration of multiple intravenous doses of 2 g ampicillin + 1 g sulbactam (Unacid^®, Pfizer), each over 15 min thrice a day.

Results

A reduced C _max, AUC_0–8 h and total clearance, a prolonged half-life, and an increased steady-state volume of distribution were observed for ampicillin. The mean estimated free C _min of 1.8 mg/L for ampicillin was higher than that predicted to be effective against Streptococcus pneumoniae. Based on an MIC₉₀ of 1 mg/L for Streptococcus pneumoniae, the calculated T > MIC and T > 4 × MIC for ampicillin was 75–100 % (median 100 %) and 12.5–100 % (median 50 %), respectively. A T > 4 × MIC of at least 50 % was achieved in 7 of 13 elderly patients with CAP.

Conclusions

Age and, probably, pneumonia did affect the pharmacokinetics of ampicillin and sulbactam. Despite the reduced C _max, adequate free C _min/MIC₉₀ ratios due to impaired renal function were observed in elderly patients with CAP. In elderly patients without renal impairment and/or in severe infection with less susceptible pathogens, more frequent dosing of ampicillin 2 g/sulbactam 1 g can be necessary to avoid the risk of underdosing in CAP.     

Concentrations of ampicillin and sulbactam in serum and in various compartments of the respiratory tract of patients

Summary After infusion of 2 g ampicillin and 1 g sulbactam the concentrations of these two -lactams were determined in serum and various compartments of the respiratory tract of 22 patients. About 30 min after the end of the infusion in 15 patients the mean serum concentration of ampicillin was 97±9.5 mg/l and of sulbactam 37.6±3.8 mg/l; in the biopsy samples of bronchial mucosa the concentration of ampicillin was 38.6±7.2 mg/kg and of sulbactam 28.1±5.2 mg/kg; in bronchial fluid the concentration of ampicillin was 0.6±0.1 mg/l and of sulbactam 0.3±0.1 mg/l (n=15). In a further seven patients serum and pleural empyema samples were analysed and compared. The mean values of C_max attained 1 to 2 h after the end of the infusion in pleural empyema were 7.6±3.1 mg/l and 6.2±1.6 mg/l for ampicillin and sulbactam, respectively. The two -lactams were eliminated markedly more slowly from empyema than from serum. These results show that ampicillin and sulbactam rapidly penetrate into various compartments of the respiratory tract and reach therapeutically active concentrations. The ratio of their concentrations (2 : 1) is largely the same as that in serum. The pharmacokinetic data therefore support the use of ampicillin/sulbactam in the perioperative prophylaxis and the treatment of bacterial infections of the lower respiratory tract.

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Konzentrationen von Ampicillin und Sulbactam im Serum und verschiedenen Kompartimenten des Respirationstraktes von Patienten

Zusammenfassung Nach Infusion von 2 g Ampicillin und 1 g Sulbactam wurden die Konzentrationen der beiden -Lactame im Serum und verschiedenen Kompartimenten des Respirationstraktes von insgesamt 22 Patienten bestimmt. In einer Gruppe von 15 Patienten betrugen etwa 30 min nach Infusion die Mittelwerte der Konzentrationen von Ampicillin und Sulbactam im Serum 97±9,5 mg/l bzw. 37,6±3,8 mg/l; in den Biopsieproben der Bronchialschleimhaut 38,6±7,2 mg/kg bzw. 28,1 ± 5,2 mg/kg und im Bronchialsekret 0,6±0,1 mg/l bzw. 0,3±0,1 mg/l. Von weiteren sieben Patienten konnten Serum- und Pleuraempyemproben bis etwa acht Stunden nach Infusion vergleichend analysiert werden. Im Pleuraempyem wurden die C_max-Mittelwerte von Ampicillin und Sulbactam 7,6±3,1 mg/l bzw. 6,2±1,6 mg/l etwa ein bis zwei Stunden nach der Infusion erreicht. Beide -Lactame wurden aus dem Empyem deutlich langsamer als aus dem Serum der Patienten eliminert. Die Ergebnisse von Patienten zeigen, daß Ampicillin und Sulbactam schnell in die verschiedenen untersuchten Kompartimente des Respirationstraktes penetrieren, dabei therapeutisch wirksame Konzentrationen erreichen und in einer ähnlichen Relation (2 : 1) wie im Serum vorliegen. Diese pharmakokinetischen Daten unterstreichen die Eignung von Ampicillin/Sulbactam für die perioperative Prophylaxe und die Therapie bakterieller Infektionen des unteren Respirationstraktes.

     

Failure of systemic antibiotics to eradicate gram-negative bacilli from the airway of mechanically ventilated very low-birth-weight infants

BACKGROUND: Gram-negative bacillary (GNB) airway colonization in mechanically ventilated newborns is associated with morbidity and mortality, which may be reduced if systemic antimicrobial therapy eradicates GNB from the airway. Efforts to do so in adults have met with variable success; similar experiences in newborns have not been reported. METHODS: From 1991 through 1998, 531 very low-birth-weight infants were mechanically ventilated longer than 2 weeks. The study group was 106 infants with GNB airway colonization. Sixty-four other neonates in whom GNB nosocomial bloodstream infections developed served as antibiotic treatment outcome control. RESULTS: Isolated from the airway were enteric (70 cases) and environmental (36 cases) GNB. Gentamicin alone or with ceftazidime (79), ceftazidime (11), piperacillin in combination with tazobactam or tobramycin (8), and tobramycin, in combination with ampicillin/sulbactam or mezlocillin (8) were the antimicrobials selected. Systemic antibiotics failed to eradicate GNB colonization in 97% of the cases. Six of the 106 infants with airway colonization died for reasons unrelated to infection. Sixty-four infants experienced 67 bloodstream infections as a result of enteric (53) and environmental (14) GNB. Gentamicin alone (23), with ceftazidime (26), or with clindamycin or ampicillin/sulbactam (9), piperacillin with tazobactam or tobramycin (3) and ceftazidime alone (6) were the antimicrobials selected. Survival occurred in 84% of the 67 nosocomial bloodstream infections. CONCLUSIONS: Systemic antibiotics do not consistently eradicate GNB from the airway of mechanically ventilated newborns, therefore its empirical use for prophylaxis or treatment of airway colonization should be discouraged.     

Perioperative antibiotic prophylaxis in general thoracic surgery.

A prospective study of the efficacy of ampicillin in combination with sulbactam, a beta-lactamase inhibitor, (A/S) in perioperative prophylaxis was performed. The study consisted of two independent parts performed at the same time. Part I included 60 patients with lobectomies and segmentectomies. Group A (A/S 1 x 3 g "single shot") was compared with group B (A/S 3 x 3 g). Superficial wound infections occurred in 3 patients of group A and in 2 patients of group B. There was no empyema. Bronchitis and pneumonia were found in 10 patients of group A and in 7 patients of group B. Part II examined 25 pneumonectomies receiving A/S 3 x 3 g for 3 days. Concentrations of ampicillin and sulbactam in serum and lung tissue were determined and showed adequate levels to cope with usual bacteria in lung surgery. There was one superficial wound infection, 2 cases of bronchitis, and 2 cases of pneumonia.