Penetration of ampicillin into human bronchial secretions

Bergogne-Bérézin, E; Berthelot, G; Kafé, H; Morel, C.

doi:10.1007/bf01659772

Infection

1979

DOI: 10.1007/bf01659772

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Penetration of ampicillin into human bronchial secretions

E Bergogne-Bérézin

G Berthelot

H Kafé

et al.

Abstract: Ampicillin concentrations in serum and bronchial secretions after oral administration of bacampicillin were evaluated. Twenty-eight hospitalized patients with acute bronchopulmonary infections received a single dose of 800 mg of bacampicillin. Samples of bronchial secretions were obtained during diagnostic bronchoscopy and blood samples were drawn simultaneously. Significant concentrations of ampicillin were found in bronchial secretions, the peak level, reached after approximately two hours, being 0.27 microg… Show more

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Cited by 11 publications

(4 citation statements)

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“…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).…”

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“…(10,26). tract using sputum or bronchial secretions as the study material have been performed (3,4,16,23 administration, but there was no corresponding increase in penetration into sputum (27). The ratio between bronchial concentrations and simultaneous concentrations in serum usually ranged between 3 and 5%.…”

mentioning

confidence: 99%

“…The ratio between bronchial concentrations and simultaneous concentrations in serum usually ranged between 3 and 5%. Local vasodilation and increased vascular permeability, which are features of inflammation, increase the penetration of ampicillin into bronchial secretions (3,16). Single-dose oral administration of 750 mg of sultamicillin in four patients with chronic respiratory tract infections resulted in ranges of peak levels in sputum of 0.2 to 1.3 and 0.13 to 0.52 ,ug/ml for sulbactam and ampicillin, respectively.…”

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

Valcke

Rosseel

Pauwels

et al. 1990

Antimicrob Agents Chemother

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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...

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

Valcke

Rosseel

Pauwels

et al. 1990

Antimicrob Agents Chemother

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“…Several alternative approaches, all with limitations, have been used to estimate tissue penetration. Sputum and bronchial studies show wide variations in results, possibly because of sample 10%), cefoxitin (25%), cefuroxime (18%), and cefotaxime (25%) (1,2,17). The penetration of tetracycline antibiotics itito bronchial secretions varies widely, as shown with minocycline (37%), doxycycline (18%), and rolitetracycline (71%).…”

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Vancomycin entry into lung lymph in sheep

May

Stratton

Denney

et al. 1987

Antimicrob Agents Chemother

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The distribution of antibiotics into target tissues is a crucial factor in therapeutic efficacy. To estimate the availability of systemically administered vancomycin to the interstitial fluid in the lung, we have used a sheep model with a chronic pulmonary lymph fistula to collect simultaneously series of plasma and pulmonary lymph specimens during a 6-h period after an intravenous dose of vancomycin (7 mg/kg). After a minor delay in transit from blood to lymph, vancomycin was completely distributed to pulmonary lymph with a ratio of free drug in lymph to free drug in plasma of 0.9. This suggests that vancomycin is an excellent choice for treating pulmonary infections by susceptible organisms.Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by staphylococci and enterococci. These pathogens are capable of causing pulmonary infections (3,4,8 RESULTS Peak levels in serum were comparable to those achieved in humans after a single dose of 7.0 mg/kg (7, 11). Immediately after infusion, total (bound plus free) vancomycin concentration in lymph was approximately 65% of total concentration in plasma. After a 30-min lag, total vancomycin concentration in lymph was at least 80% of the corresponding total concentration in plasma. Elimination of vancomycin from both sheep plasma and lymph appeared to be a multiexponential process (Fig. 1). Terminal half-lives and their associated rate constants in plasma and lymph were similar. Protein concentrations were slightly lower than those of 1689

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Aminopenicillins: Concluding remarks

Bergan

1979

Infection

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This symposium has focused on the bacteriological, pharmacokinetic, therapeutic, and adverse effects of the aminopenicillins. The compounds which are currently being assessed are primarily amoxycillin, ampicillin, bacampicillin, pivampicillin, and talampicillin. The three last mentioned are prodrugs which upon gastrointestinal absorption are rapidly split to yield circulating ampicillin. Pharmacokinetics and side-effects are reasons why one may narrow the selection of most suitable compounds within this group down to three. Ampicillin and amoxycillin are primary choices for parenteral dosage, and amoxycillin and bacampicillin the most suitable for oral therapy.

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Penetration of ampicillin into human bronchial secretions

Cited by 11 publications

References 5 publications

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

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

Vancomycin entry into lung lymph in sheep

Aminopenicillins: Concluding remarks

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