Lorraine C. Steele

Antimicrobial susceptibility patterns of Nocardia asteroides.

Testing of the susceptibility to 12 antimicrobial agents, including beta-lactams, aminoglycosides, ciprofloxacin, and erythromycin, was performed by broth microdilution on 78 consecutive clinical isolates of Nocardia asteroides. Surprisingly, a limited number of patterns of susceptibility were identified that included all drug classes, with 95% of isolates exhibiting one of five patterns. One group (17%) exhibited resistance to the broad-spectrum cephalosporins, one group (18%) was susceptible to both ampicillin and erythromycin, one group (17%) was susceptible to ampicillin and carbenicillin but intermediate in susceptibility to imipenem, and the most common group (35%) was resistant to ampicillin but susceptible to the broad-spectrum cephalosporins and imipenem. The most active parenteral agents were amikacin (95%), imipenem (88%), ceftriaxone (82%), and cefotaxime (82%), while the most active oral agents were the sulfonamides (100%), minocycline (100%), and ampicillin (40%). Additional studies are needed to determine whether differences in beta-lactamases relate to varying beta-lactam resistance and whether taxonomic differences that correlate with the different susceptibility groups can be identified.

Susceptibility testing of nocardia species for the clinical laboratory

Not all patients are able to tolerate or show a favorable response to the treatment of choice for Nocardia, the sulfonamides. Many new drugs are available with good activity against N. asteroides, the most common pathogenic species, although susceptibility to these agents, including amikacin, amoxicillin/clavulanic acid, and the third generation cephalosporins, is variable. For these and other reasons, we recommend routine susceptibility testing of Nocardia. Disk diffusion testing on Mueller Hinton agar is the best currently available clinical method. A suggested control strain and tentative susceptible and resistant breakpoints for 12 antimicrobial agents are provided. This includes agents not previously evaluated, including cefotaxime, amikacin, ciprofloxacin, and doxycycline. The zones of inhibition were all larger than those currently used by the NCCLS for rapidly growing bacteria, and the disk breakpoints generally fit best with the MIC breakpoints used with the dilution susceptibility method (M7-T). A broth microdilution MIC method is described that showed good correlation with disk diffusion results, but need additional study. Because of limited experience in most laboratories with this species, reliance on a good reference laboratory for confirmatory susceptibility testing is recommended. Beta-lactamase testing is not helpful, as almost all Nocardia produce beta-lactamase, although many isolates retain susceptibility to selected beta-lactams.

Amoxicillin-clavulanic acid in the treatment of lower respiratory tract infections caused by beta-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis.

Twenty-one adult patients hospitalized with lower respiratory tract infections due to Branhamella catarrhalis or Haemophilus influenzae or both were treated with the combination of oral amoxicillin and potassium clavulanate (Augmentin) in an open, noncomparative clinical trial. Diseases included pneumonia, empyema, and exacerbations of bronchiectasis and chronic lung disease. Thirteen of 16 B. catarrhalis and six of nine H. influenzae isolates were beta-lactamase positive. The patients with B. catarrhalis were treated for a mean of 5.3 days, and those with H. influenzae were treated for a mean of 7.0 days. The overall response to therapy was excellent, with 18 of 19 beta-lactamase-producing strains eradicated on therapy. One patient secondarily infected with Pseudomonas aeruginosa was a clinical failure, and two patients with H. influenzae who became culture positive again after therapy were considered microbiologic failures. Gastrointestinal side effects (especially nausea) were common, although all patients completed a course of therapy. Sputum levels of amoxicillin were surprisingly low (less than 0.05 to 0.54 micrograms/ml), a finding which may explain the high relapse rate (22%) seen with H. influenzae, as these are below the usual MICs of amoxicillin for this organism. The combination of amoxicillin plus potassium clavulanate appears to be an excellent drug for treatment of beta-lactamase-producing strains of these two species, although mild gastrointestinal side effects are common.

Partial characterization of Nocardia farcinica beta-lactamases.

The beta-lactamases obtained from culture supernatants and cell extracts of 26 clinical strains and 5 reference strains of Nocardia farcinica were partially characterized. The enzymes exhibited two patterns on isoelectric focusing (IEF). beta-Lactamases from the majority of the 31 strains (87%) including the 5 reference strains exhibited two major bands with pIs of 4.56 and 4.49. The remaining strains had two similar major bands but with slightly higher pIs. Culture supernatants and cell extracts exhibited identical patterns. The two sets of enzymes were functionally indistinguishable by substrate and inhibitor profiles and lack of inducibility. By disk testing, ampicillin, amoxicillin, ticarcillin, amoxicillin-clavulanic acid, and imipenem were highly synergistic with cefotaxime. The enzymes were primarily penicillinases and hydrolyzed cephalosporins at rates of < or = 12% of those for penicillins. N. farcinica beta-lactamases were susceptible to inhibition by clavulanic acid and BRL 42715, exhibiting 50% inhibitory concentrations of 0.025 to 0.045 micrograms/ml (0.12 to 0.22 microM) and 0.05 to 0.1 micrograms/ml (0.31 to 0.63 microM), respectively, less susceptible to tazobactam, and least susceptible to sulbactam, cloxacillin, and imipenem. The beta-lactamases of N. farcinica are believed to mediate penicillin resistance and may play a secondary role in extended-spectrum cephalosporin resistance. The close similarity among N. farcinica beta-lactamases and their distinct differences from beta-lactamases of other Nocardia species support the taxonomic identity of this species. Images

Susceptibilities of Mycobacterium fortuitum biovariant fortuitum and the unnamed third biovariant complex to heavy-metal salts.

Fifty-three clinical isolates of Mycobacterium fortuitum were tested for susceptibility to heavy-metal salts and antimicrobial agents. The isolates exhibited a bimodal distribution for several heavy metals including mercury, whose resistance is often plasmid mediated. There was a biovariant difference in the incidence of resistance, and resistance to several metal ions was often observed together. There was no apparent relationship between resistance to heavy-metal salts and resistance to antimicrobial agents such as tetracycline.