Deborah A. Gerstein

Suppression of Intrinsic Resistance to Methicillin and Other Penicillins in Staphylococcus aureus

The pH of the medium in which staphylococcal susceptibility to penicillins was determined was found to make a profound difference (128- to 8,000-fold) in the expression of “intrinsic” resistance, whereas β-lactamase-mediated resistance was only slightly affected by pH; methicillin-resistant staphylococci that are β-lactamase-negative are models of pure intrinsic resistance, and the common β-lactamase-producing organisms (methicillin-susceptible) are examples of pure β-lactamase-mediated resistance. Methicillin-resistant staphylococci were unable to express their resistance at pH 5.2. However, growth of methicillin-resistant organisms in acid (pH 5.2) medium, followed by susceptibility testing at pH 7.4, showed no elimination of the genotype for intrinsic resistance, indicating that the pH effect was due to suppression, rather than to elimination of the gene determining the intrinsic resistance. These pH changes had little effect on the susceptibility of staphylococci that possessed neither intrinsic resistance nor β-lactamase-mediated resistance. Thus, the suppression of “intrinsic” resistance was highly specific, and probably not the result of a change in ionization of the antibiotic, which would have been expected to affect all cells essentially equally. It is unlikely that foci of inflammation in man become sufficiently acid to suppress methicillin resistance of the staphylococci causing infection and inflammation.

Serum Glutamic Oxalacetic Transaminase: False Elevations during Administration of Erythromycin

Abstract Transient and sometimes marked elevations of serum glutamic oxalacetic transaminase were found in each of seven young adult male volunteers by a standard colorimetric assay after oral administration of one or two courses of 4 gm of erythromycin estolate. These elevations were shown to be due not to the enzyme but to an unidentified, trypsin-stable substance related to the administration of the antibiotic.

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 of analogues to inhibit destruction of antibiotic by bacterial enzymes (more specifically penicillinases) and (2) adfustment of the pH of the medium to maximize antibiotic activity. Both were applied to patients with infections caused by gram‐negative bacilli. Ampicillin plus a ±‐Iactamase 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 allcalinize the urine permitted the use of this antibiotic in a much reduced dose.