In Vitro Studies of the Combined Effect of Ampicillin and Sulfonamides on Nocardia asteroides and Results of Therapy in Four Patients

Abstract

The minimal inhibiting concentrations (MIC) of ampicillin, trisulfapyrimidines, and various combinations of these drugs were determined for four clinical isolates of Nocardia asteroides on Mueller-Hinton agar. The combination of ampicillin and sulfonamides was found to be synergistic for three of the four isolates when an inoculum of 10 3 to 10 4 organisms per ml was used. (Synergism was defined as occurring when the MIC of each of the drugs in combination was one-quarter or less of the MIC of each drug alone.) All four isolates were inhibited by concentrations of the drugs in combination that were clinically achievable. Combined therapy with ampicillin and sulfonamides was used in four immunologically suppressed renal transplant patients who had pulmonary infection with N. asteroides . Clinical improvement was noted within 2 weeks in all patients, and the pulmonary infiltrates cleared by 6 months in three patients. One patient died from an unrelated illness 10 days after starting therapy. The disease was arrested in two patients who were maintained on full immunosuppressive therapy.

Nocardia species: host-parasite relationships

“…Since this first report, several hundred cases of primary pulmonary nocardiosis occurring in both healthy and immunocompromised individuals have been described in the literature. The pathologic feature of pulmonary nocardiosis is usually a suppurative response, but a granulomatous response or a mixture of these resulting in radiographic presentations that are pleomorphic and not specific may occur (38,237,393,395,506,734). The manifestation within the lungs may vary from a mild, diffuse infiltration to a lobar or multilobar consolidation (Fig.…”

“…1A). There may be solitary masses, reticulonodular infiltrates, large irregular nodules (frequently with cavitation), interstitial infiltrates, and pleural effusions (38,237,393,395,411,478,506,527,734). The lesions produced in the lungs may be necrotizing abscesses that usually are not encapsulated, or they may be sharply circumscribed (273,393).…”

“…There are reports of Nocardia spp. colonizing airway passages without inducing disease; however, on the basis of studies with animal models, these should probably be interpreted as representing subclinical infections rather than simple colonization (37, 59-61, 64, 67, 69-71, 74, 82, 89, 122, 203, 253, 254, 388, 566, 734 (18,38,186,198,203,237,247,253,254,393,395,478,486,506,527,623,703,734 [303,311,702], wood splinter [180], traumatic accident [352,378], bullet wound [283,463,468], insect bite [156,277], or animal bite [429]). Thus, when lesions are found at two or more locations within the body, the infection is defined as systemic or disseminated nocardiosis.…”

Antibiotic Sensitivity of Some Nocardioform Bacteria and its Value as a Criterion for Taxonomy

“…It is for these reasons that other antimicrobial agents are now used, in conjunction with, or as an alternative to, the sulphonamides. It is by no means clear which additional or alternative drugs should be recommended; cycloserine (Rhoades, Riley & Muchmore, 1961 ;Hoeprich et al 1968), ampicillin (Orfanakis et al 1972)~ septrin (Baikie, MacDonald & Mundy, 1970), and erythromycin and sulphone (Vasarinsh, 1968) have been tried. It can be concluded from the present study that erythromycin, miconazole nitrate and the aminoglycoside antibiotics, especially gentamycin and tobramycin, might be effective in treating Nocardia infections.…”

“…Most of these studies have provided little data of taxonomic value because the test strains have usually been restricted to a few poorly described clinical isolates (Wilson & Williams, 1966;Black & McNellis, I 970;Orfanakis, Wilcox & Smith, 1972). In similar studies Bach, Sabath & Finland (1973 b) and Lerner.…”