Imipenem sensitive pretherapy isolates (MICs 1-2 mg/l) and the corresponding resistant posttherapy isolates (MICs 16 mg/l) of Pseudomonas aeruginosa from three patients undergoing imipenem treatment were analyzed to establish the resistance mechanism. The identity of pyocin types, serotypes, DNA restriction endonuclease profiles and plasmid profiles strongly suggested isogenicity of pre- and posttherapy isolates. The imipenem resistant posttherapy isolates showed cross-resistance only to another carbapenem, meropenem. There were neither qualitative nor quantitative differences between pre- and posttherapy isolates in beta-lactamase production. Affinity of the penicillin-binding proteins 1A, 1B, 2, 3, 4,4' and 5 for [14C]imipenem was the same in pre- and posttherapy isolates. One-dimensional and two-dimensional gel electrophoresis of outer membrane protein preparations showed diminished expression of an outer membrane protein of about 46.5 and 47.5 kilodaltons, respectively, in the posttherapy isolates. This protein had an apparent isoelectric point of about pH 5.2 in two-dimensional gel electrophoresis. Growth in proteose peptone no. 2 broth did not reduce expression of this outer membrane protein, which spoke against its identity with the outer membrane protein D1. The permeability of the outer membrane for imipenem was reduced in the posttherapy isolates, since addition of 0.5 or 0.25 of the MIC of the permeabilizing agent ethylene-diaminetetraacetate reduced the MICs of imipenem for all isolates from each patient to the same (susceptible) level. The diminished expression of one of the outer membrane proteins might be the reason for this reduced permeability.

Minimal inhibitory concentrations of the monobactam carumonam (RO 17-2301) and twelve other antimicrobials were determined using agar dilution against 140 recent non-replicate clinical isolates of Pseudomonas aeruginosa. The most active drugs were ciprofloxacin, amikacin, imipenem and ceftazidime, inhibiting 96, 91, 90 and 86 percent of the strains, respectively, at or below the susceptibility threshold. The monobactams carumonam and aztreonam were active against 78 and 65 percent of the strains, respectively. Tobramycin inhibited 68 percent of the strains, and gentamicin and netilmicin 50 and 21 percent, respectively. Analysis of correlation coefficients revealed a low correlation between imipenem and the other beta-lactams and a remarkably good correlation between the beta-lactams (excepting imipenem) and the aminoglycosides.

Imipenem was examined with standardized agar dilution procedures against a wide range of bacteria. Geometric mean MICs against the genera Escherichia, Klebsiella, Enterobacter, Citrobacter and Serratia were 0.1-0.4 mg/l, and Proteus and Providencia spp. were inhibited by 0.25-4 mg/l. Acinetobacter calcoaceticus var. anitratum strains were inhibited by concentrations ranging from 0.12-0.5 mg/l. Methicillin-susceptible staphylococci were highly susceptible to the drug (MICs: less than or equal to 0.03 mg/l) and enterococci were inhibited by 0.25-16 mg/l. Most of the multi-resistant JK corynebacteria were resistant to imipenem. Imipenem was more active than any other beta-lactam against methicillin-resistant staphylococci; this was also demonstrated in a population analysis. Imipenem-resistant minorities in populations, however, were also observed. Cefotaxime-resistant and -intermediate Enterobacter and Citrobacter strains were inhibited by concentrations of 0.5 mg/l or less. No third-generation cephalosporin nor any other beta-lactam showed similarly high activity against these groups of organisms. Among 20 ceftazidime-resistant and 20 ceftazidime-susceptible isolates of Pseudomonas aeruginosa, no strain was resistant and only five ceftazidime-resistant strains were intermediately susceptible (MIC, 8 mg/l) to imipenem.

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Mycobacterial infections were confirmed in 629 HIV-infected persons (1.4%). Five patients had a generalized infection with Mycobacterium avium complex (MAC), four an extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (M. tbc). In general, the tuberculosis was the first severe opportunistic infection, while infections with MAC were more frequent in patients with already manifest AIDS. Common to all patients were a septic temperature and definite shift to the left of neutrophil granulocytes. Four of five patients with MAC also had diarrhoea, and three of four with tuberculosis additionally had peripheral lymphomas. The chest x-ray films were normal in six of the nine patients. The diagnosis was made in six patients primarily by the microscopic demonstration of acid-fast bacteria in lymph node tissue or stool, in three patients by culture from blood or liver tissue. Microscopic stool examination was helpful: in three of five patients with MAC and one of two with M. tbc in the stool culture, acid-fast bacteria had already been demonstrated. In an individual case MAC infections could not be distinguished either clinically or morphologically from infections with M. tbc, but only by culture.