Penetration of ampicillin and sulbactam in the lower airways during respiratory infections

Abstract

We studied the penetration of ampicillin-sulbactam in the alveolar lining fluid (ALF) of eight patients after intravenous administration of 2,000 mg of ampicillin and 1,000 mg of sulbactam three times daily over 30 min. Bronchoalveolar lavage was performed on day 3, 30 min after the end of the morning drug administration. The mean penetration ratios (i.e., the ratios of the concentrations in ALF versus those in serum) were 53% (standard error, 12%) and 611% (standard error 31%) for ampicillin and sulbactam, respectively. The concentration ratio of ampicilin versus sulbactam in serum was not significantly different from that in ALF. From a pharmacokinetic point of view, ampicillin-sulbactam is a good choice for treatment of infectious exacerbation of chronic obstructive pulmonary disease and community-acquired bacterial pneumonia, since the concentrations of both drugs in ALF exceed the MICs for the respiratory pathogens responsible.The clinical outcome of bacterial lower respiratory tract infections is a function of two, main factors: the efficacy of the host defense mechanisms and institution of appropriate antimicrobial therapy. The antimicrobial drug concentration at the site of infection is supposed to be a determinative element for effective antimicrobial therapy (2). This concentration should equal or exceed the MIC for the respiratory pathogen responsible (3,17,22). The final bioactive antibiotic concentrations in the bronchial wall and in secretions and in the alveolar lining fluid (ALF), which are the sites of infection in the lower respiratory tract, are the results of a complex and dynamic process (1, 2, 14).We evaluated the pharmacokinetic behavior of parenterally administered ampicillin-sulbactam in serum and studied the disposition of both drugs in ALF by using the bronchoalveolar lavage (BAL) technique. BAL has been used to study the chemical compositions of ALF in both normal and pathologic situations, such as interstitial lung disease and asthma. With this technique, the concentrations of immunoglobulins, complement components, surfactant, a2-macroglobulin, ao-antitrypsin, and several mediators have been determined (8,28). Only a few studies have used BAL for evaluation of the concentrations of drugs such as corticosteroids and antibiotics in ALF (5-7).Sulbactam is a semisynthetic P-lactamase inhibitor (10,20). In combination with ampicillin, it restores and extends the antibacterial activity of ampicillin to include some ,Blactamase-producing strains of bacteria, such as Haemophilus influenzae and Branhamella catarrhalis, that would otherwise be resistant (10,15,24). The penetration and ampicillin/sulbactam ratio in ALF have not been studied previously. MATERIALS AND METHODSPatients. Seven males and one female (average age, 71 years) with bacterial respiratory tract infections were invited to participate in the study after giving informed consent. All patients had chronic obstructive pulmonary disease and were hospitalized because of infectious exacerbation. Five * Corresponding author.patients...

In Vitro Activities of the β-Lactamase Inhibitors Clavulanic Acid, Sulbactam, and Tazobactam Alone or in Combination with β-Lactams against Epidemiologically Characterized Multidrug-Resistant Acinetobacter baumannii Strains

“…It has been shown previously that ␤-lactamase inhibitors, sulbactam in particular, have intrinsic activity against A. baumannii (1,12,16,27,29). The activity of ␤-lactam-␤-lactamase inhibitor combinations used at a fixed ratio of ␤-lactam to inhibitor is reflected mainly by the MICs of the respective inhibitors alone.…”

“…This can be attributed to the intrinsic activity of the inhibitors and not to ␤-lactamase inhibition (7). Sulbactam has good intrinsic antimicrobial activity against multidrug-resistant Acinetobacter strains at concentrations readily achievable in human serum (29) and may therefore have some therapeutic implications in the treatment of infections caused by multidrug-resistant A. baumannii infections. However, A. baumannii strains with elevated sulbactam MICs (Ն32 mg/liter) exist, and the majority of these strains were outbreak related.…”

“…Alternative therapies are therefore needed. The ␤-lactamase inhibitors sulbactam and tazobactam have been reported to possess intrinsic antibacterial activity against Acinetobacter strains at concentrations achievable in humans (ϳ40 and 5.5 to 51 mg/ liter, respectively) (1,20,26,28,29). Sulbactam combinations are bactericidal against A. baumannii in in vivo models (21,32).…”

Prevalence, Genotyping of Escherichia coli and Pseudomonas aeruginosa Clinical Isolates for Oxacillinase Resistance and Mapping Susceptibility Behaviour

“…Sulbactam has been reported superior to clavulanic acid and tazobactam and may represent an alternative treatment option for infections due to multiresistant organisms [36]. It has reported that sulbactam has good intrinsic antimicrobial activity against multidrug-resistant Acinetobacter strains at concentrations readily achievable in human serum and may therefore have some therapeutic implications in the treatment of infections caused by multidrug-resistant A. baumannii infections whereas tazobactam and clavulanic acid were only moderately active or inactive [37].…”

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients

“…Concentrations in ELF were well correlated with concentrations in plasma, with mean ratios of 10.8 and 6.05% in groups A and B, respectively. Previous studies have evaluated the penetration of antibiotics into the ELF with very different results: the ratios of concentrations in ELF to concentrations in serum were 17% for roxithromycin (3), 53% for ampicillin, 51% for sulbactam (16), and 50% for tobramycin (2). These variations could have resulted from two main differences in these studies.…”