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

Abstract

After infusion of 2 g ampicillin and 1 g sulbactam the concentrations of these two beta-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 Cmax 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 beta-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.

The American Association for Thoracic Surgery consensus guidelines for the management of empyema

“…For patients with community-acquired pleural empyema in whom the risk for methicillin-resistant S aureus and highly resistant gram-negative infection is low, a second-generation or a nonpseudomonal, third-generation cephalosporin (eg, ceftriaxone) or an aminopenicillin with b-lactamase inhibitor (eg, ampicillin/sulbactam) will provide activity against the most commonly identified organisms. [54][55][56][57][58] Anaerobic organisms should be treated empirically and, whereas ampicillin/sulbactam is active against a range of anaerobes, ceftriaxone requires the addition of an agent such as metronidazole. Clindamycin is a suitable alternative to metronidazole for most upper gastrointestinal and respiratory anaerobic infections.…”

Outcomes of Adjunctive Therapy with Intravenous Cefoperazone-Sulbactam for Ventilator-Associated Pneumonia Due to Carbapenem-Resistant Acinetobacter baumannii

“…Previous animal studies and a study in healthy human volunteers have demonstrated low levels of colistin in lung tissue and epithelial lining fluid after administration of IV colistin. 11,13,14…”

“…10 Furthermore, previous studies showed sufficient concentration of sulbactam in the lung tissues of animals and healthy human subjects to achieve therapeutic levels for treatment of pneumonia due to A. baumannii. [11][12][13][14] Hence, adjunctive therapy with intravenous cefoperazone-sulbactam (CEP-SUL) has been employed in addition to colistin and other agents for the treatment of CRAB mediated VAP in our hospital. In this retrospective analysis, the clinical outcome, characteristics, and factors associated with mortality of VAP patients due to CRAB were explored and the therapeutic effects of CEP-SUL adjunctive therapy were analyzed.…”

Ampicillin/sulbactam: Its potential use in treating infections in critically ill patients

“…Similarly, favourable penetration resulting in therapeutic exposure has been shown for other sites including costal cartilage, middle ear fluid, peritoneal fluid, intestinal mucosa, prostatic and appendicular tissue, sputum and peritonsillar abscess pus [43,44]. For infections involving the lower respiratory system, particularly VAP, achieving effective epithelial lining fluid concentrations of antibiotics can be challenging for some therapies [45,46], although SAM appears to penetrate well [47,48]. Adequate concentrations in abdominal tissues against common pathogens, i.e.…”