Increasing the usefulness of antibiotics: Treatment of infections caused by gram-negative bacilli

Resistance of gram-negative bacteria to many antibiotics often necessitates the use of relatively toxic antibiotics to treat infections caused by organisms that are resistant to less toxic ones. However, some relatively nontoxic antibiotics that appear to be ineffective against many gram-negative bacilli by conventional tests can, in some instances, be made much more active by appropriate adjunctive measures. The measures studied were: (1) the use o f analogues to inhibit destruction o f antibiotic by bacterial enzymes (more specifically penicillinases) and (2) adjustment o f the pH o f the medium to maximize antibiotic activity. Both were applied to patients with infections caused by gram-negative bacilli. Ampicillin plus a β-lactamase inhibitor, cloxacillin, were used to treat a patient with endocarditis due to Enterobacter cloacae. Gentamicin was found to be 100 or more times as active in vitro at pH 8.5 as at pH 5.0 against most strains of gram-negative bacilli that were studied. The concomitant use of bicarbonate or acetazolamide to alkalinize the urine permitted the use of this antibiotic in a much reduced dose.