Comparison of antimicrobial in vitro activities against Streptococcus pneumoniae independent of MIC susceptibility breakpoints using MIC frequency distribution curves, scattergrams and linear regression analyses.

Comparing in vitro activities of antimicrobial agents against Streptococcus pneumoniae using per cent susceptible to recommended MIC breakpoints is not optimal. In this study, MICs of penicillin G, ampicillin/sulbactam, ceftriaxone, cefuroxime, erythromycin, tetracycline, trimethoprim/sulfamethoxazole, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin were determined for 646 strains. Drug activities were compared using MIC frequency distribution curves, scattergrams and linear regression analyses of MICs (log2). MIC frequency distributions did not always correspond to recommended breakpoints for distinguishing susceptible, intermediate and resistant strains. Penicillin G, ampicillin/sulbactam and ceftriaxone had similar activities and were each c. 1-1.5 dilution steps more active than cefuroxime. For all beta-lactam drug pairs, there was a high correlation of MICs with regression line slopes (a approximately equal to 1) and coefficients of determination (R(2) = 0.90-0.97). Although beta-lactam-resistant strains were more likely to be resistant to erythromycin, tetracycline and/or trimethoprim/sulfamethoxazole than were beta-lactam-susceptible strains, MIC correlations were relatively poor (R(2) = 0.14-0.46), as they were when the non-beta-lactam drugs were compared with each other (R(2) = 0.10-0.25). Trovafloxacin and moxifloxacin were each c. 2.5 dilution steps more active than ciprofloxacin and levofloxacin. There was no correlation of quinolone MICs with MICs of any other drug class (R(2) 0.02). Among the quinolones, however, there was a high correlation of MICs with a approximately equal to 1 and R(2) = 0.81-0.92. With the quinolone drug pairs, lines of best fit were second-order polynomial equations, consistent with a dissociation of low level resistance mechanisms. In summary, beta-lactam and quinolone MICs were predictable within drug classes and testing multiple derivatives within each class is probably not necessary. Although there was some relationship between beta-lactam, erythromycin, tetracycline and trimethoprim/sulfamethoxazole MICs, predictability of MICs between drug classes was poor. There was no relationship between quinolone MICs and MICs of any of the other drugs tested.

The utility of non-beta-lactam antimicrobial MICs as markers to distinguish oxacillin-resistant from oxacillin-susceptible strains of Staphylococcus epidermidis.

Among 6,068 strains of Staphylococcus epidermidis, 75.5% were oxacillin-resistant. Oxacillin-susceptible strains were more frequently susceptible to erythromycin, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, and tetracycline than oxacillin-resistant strains. With the exception of erythromycin, non-beta-lactam MICs were less discriminatory for identifying oxacillin-resistant strains with oxacillin MICs < or = 2 micrograms/ml than for those with oxacillin MICs > or = 4 micrograms/ml.

In vitro activities of quinolones, beta-lactams, tobramycin, and trimethoprim-sulfamethoxazole against nonfermentative gram-negative bacilli.

From 1991 to 1995, 8,975 nonfermentative gram-negative bacilli were isolated from patients at The Ohio State University Medical Center: 71% Pseudomonas aeruginosa, 14% Stenotrophomonas maltophilia, 7.6% Acinetobacter baumannii, and < 2% each of 25 other species. The MICs of trovafloxacin (CP-99,219), ciprofloxacin, ofloxacin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, ceftazidime, cefoperazone, ceftriaxone, imipenem, tobramycin, and trimethoprim-sulfamethoxazole (TMP-SMZ) were determined for 308 isolates, representing 13 species, by a standardized broth microdilution method. The activities of all drugs were species dependent. The fluoroquinolones had inconsistent activity against most species, although several relatively uncommon nonfermenters were consistently susceptible or resistant. Trovafloxacin was considerably more active than ciprofloxacin and ofloxacin against S. maltophilia, A. baumannii, and several less common species. Among the beta-lactams, relative activities varied considerably; overall, imipenem had the broadest spectrum of activity but was inactive against S. maltophilia and Burkholderia cepacia isolates. Tobramycin and TMP-SMZ had stereotypic spectra of activity. Tobramycin was active against most species except S. maltophilia, Alcaligenes xylosoxidans subsp. xylosoxidans, Burkholderia spp., and Weeksella virosa. TMP-SMZ was active against most species except P. aeruginosa and Pseudomonas fluorescens-putida. A review of laboratory records indicated few changes in susceptibility patterns from 1991 to 1995; the only clear trend was toward increasing P. aeruginosa resistance to all classes of drugs.

Emergence of bacterial resistance to imipenem and ciprofloxacin in a university hospital.

We have continuously monitored the in-vitro activities of imipenem and ciprofloxacin against large numbers of non-fastidious clinical isolates. After eight years of use, 97-100% of Enterobacteriaceae and Acinetobacter baumannii remained susceptible to imipenem, but susceptibility of Pseudomonas aeruginosa declined from 100% to 91%. After six years of use, 94%-100% of Enterobacteriaceae (except Providencia stuartii) remained susceptible to ciprofloxacin but susceptibility of P. stuartii, A. baumannii and P. aeruginosa declined from 100% to 46%, 66% and 84%, respectively. Oxacillin-resistant staphylococci were considered to be resistant to imipenem and all beta-lactams. There were no quinolone-resistant staphylococci observed in 1986, but susceptibilities of Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus to ciprofloxacin decreased to 85-93% for oxacillin-susceptible strains and to 7-39% for oxacillin-resistant strains. Enterococcus faecalis has remained susceptible to imipenem and the modal MIC of ciprofloxacin has remained 1 mg/L; however, susceptibility to ciprofloxacin 2 mg/L decreased from 94% to 64%. Imipenem-quinolone cross-resistance was observed for staphylococci but not for P. aeruginosa.

Isolation of fluconazole-resistant Candida albicans from human immunodeficiency virus-negative patients never treated with azoles.

Isolation of fluconazole-resistant strains of Candida species from human immunodeficiency virus (HIV)-infected patients after repeated or continuous courses of treatment has been reported with increasing frequency. During 1991-1992, MICs of fluconazole for 139 Candida albicans isolates from our institution were bimodally distributed: 102 strains were susceptible (MICs, < or = 4 micrograms/mL) and 37 were resistant (MICs, > or = 8 micrograms/mL). There was incomplete cross-resistance between fluconazole and ketoconazole or miconazole, and there was no cross-resistance between azoles and amphotericin B or flucytosine. Twenty of the 37 fluconazole-resistant strains were isolated from 17 HIV-negative patients, some with systemic infections, who had never been treated with azoles. There were no differences in characteristics or risk factors for those patients as compared with those for an equal number of HIV-negative patients from whom fluconazole-susceptible strains were isolated. Among patients with systemic infection, 6 (50%) of 12 with infection caused by fluconazole-resistant strains survived and 11 (69%) of 16 with infection caused by fluconazole-susceptible strains survived (P = .54). Survival was not found to be related to treatment regimen, but the number of patients was small. The emergence of fluconazole-resistant C. albicans among HIV-negative patients never exposed to azoles is of concern.

Penicillinase production and in vitro susceptibilities of Staphylococcus lugdunensis.

Of 59 clinical isolates of Staphylococcus lugdunensis, 76% were beta-lactamase negative, with penicillin G MICs of less than or equal to 0.13 microgram/ml, and 24% were beta-lactamase positive, with penicillin MICs of greater than or equal to 0.5 microgram/ml. Bimodal distributions were observed also with ampicillin, ampicillin-sulbactam, and amoxicillin-clavulanate. All strains were susceptible to oxacillin, cephalothin, gentamicin, rifampin, and vancomycin; 98% were erythromycin susceptible.

In vitro susceptibilities of four species of coagulase-negative staphylococci.

The in vitro susceptibilities of 260 strains of coagulase-negative staphylococci to penicillin G, oxacillin, nafcillin, methicillin, cephalothin, and seven non-beta-lactam antimicrobial agents were determined and compared with the susceptibilities of 54 strains of Staphylococcus aureus with known patterns of susceptibility. Penicillin G susceptibility for S. aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis was readily determined by using beta-lactamase tests with induced cells and with a standardized microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to the coagulase-negative species. Percentages of organisms susceptible were as follows: S. epidermidis, 7%; S. haemolyticus, 5%; and S. hominis, 47%. Oxacillin susceptibility for these four species was readily determined by using a modification of the microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to S. haemolyticus and S. hominis, but alternate criteria were necessary for S. epidermidis. Percentages of organisms susceptible were as follows: S. epidermidis, 29%; S. haemolyticus, 36%; and S. hominis, 97%. Staphylococcus saprophyticus differed from the other staphylococcal species; all strains were beta-lactamase negative and were penicillin susceptible but had higher penicillin G MICs than did susceptible strains of the other species. There was total cross resistance among the penicillinase-resistant penicillins and cephalothin for the coagulase-negative staphylococci as well as for S. aureus; oxacillin MICs were more reliable than MICs of the other drugs or a standardized disk diffusion test for distinguishing resistant from susceptible strains. Vancomycin, rifampin, and ciprofloxacin were consistently active against all staphylococci. Erythromycin, clindamycin, gentamicin, and trimethoprim-sulfamethoxazole were more active against oxacillin-susceptible staphylococci than against oxacillin-resistant staphylococci.

Biotypes of serologically nontypable Haemophilus influenzae isolated from the middle ears and nasopharynges of patients with otitis media with effusion.

A biotype analysis was performed on serologically nontypable Haemophilus influenzae isolates from the middle ear effusions and nasopharynges of 33 children with chronic otitis media with effusion (serous otitis media). Over 50% of the H. influenzae isolates from the middle ears belonged to biotype II. The incidence of beta-lactamase production was 17%. The results of this study indicate that future clinical or experimental investigations of chronic otitis media with effusion induced by serologically nontypable H. influenzae should focus on this clinically important biotype.

In vitro susceptibilities of Aeromonas hydrophila to 32 antimicrobial agents.

Minimal inhibitory concentrations of 32 antimicrobial agents for 20 strains fo Aeromonas hydrophila were determined by a microdilution method. Moxalactam was the most active drug tested. All strains were also susceptible to clinically achievable concentrations of mecillinam, cefamandole, cefuroxime, cefotaxime, aminoglycosides (except streptomycin), tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.

In vitro susceptibilities of nonfermentative gram-negative bacilli other than Pseudomonas aeruginosa to 32 antimicrobial agents.

The animal inhibitory concentrations of 32 antimicrobial agents for 322 strains of non-fermentative gram-negative bacilli, representing 30 species and unnamed groups other than Pseudomonas aeruginosa, were determined in cation-supplemented Mueller-Hinton broth with use of a microdilution method. The activities of beta-lactam antibiotics varied, but azlocillin, mezlocillin, piperacillin, cefotaxime, and moxalactam consistently were more active than were available penicillins and cephalosporins; the penicillin-like antibiotic mecillinam was less active. The activities of the aminoglycoside antibiotics were similar to each other although streptomycin and sometimes kanamycin were less active than the other aminoglycosides. Although minocycline and doxycycline usually were more active than tetracycline, the percentages of strains susceptible to the first two drugs at concentrations achievable in vivo were only occasionally higher than the percentage of strains susceptible to tetracycline. The activity of trimethoprim-sulfamethoxazole was variable. Chloramphenicol, erythromycin, clindamycin, and vancomycin were relatively inactive against most of the organisms tested, but the high degrees of activity of these drugs against specific species or strains, particularly those that were resistant to many drugs, indicated potential clinical usefulness of these agents.

Minimal inhibitory concentrations of 34 antimicrobial agents for control strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.

The use of control strains of bacteria is important to monitor the accuracy and precision of antimicrobial susceptibility testing. Knowledge of the minimal inhibitory concentrations of commonly used organisms would be useful to achieve a degree of inter- as well as intra-laboratory reproducibility. The minimal inhibitory concentrations of 34 antimicrobial agents for control strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853, as determined by a microdilution method in cation-supplemented Mueller-Hinton broth, are reported.

Effect of divalent cation concentrations on the antibiotic susceptibilities of nonfermenters other than Pseudomonas aeruginosa.

The effects of supplementing Mueller-Hinton broth with calcium and magnesium on the minimal inhibitory concentrations (MICs) of eight aminoglycosides, colistin, tetracycline, and carbenicillin for 11 nonfermenters other than Pseudomonas aeruginosa were studied and compared with the effects for Escherichia coli and P. aeruginosa. MICs were simultaneously performed in unsupplemented Mueller-Hinton broth and Mueller-Hinton broth supplemented to contain 5 mg of calcium and 2.5 mg of magnesium per dl. Changes in MICs were expressed as the increases in the number of log(2) concentrations caused by supplementation. The usual increases in MICs of aminoglycosides caused by supplementation were: zero concentrations for E. coli, one to six concentrations for P. aeruginosa, and one to two concentrations for most other nonfermenters. The largest increases (five to six concentrations) were observed with gentamicin and P. aeruginosa. The usual increases in MICs of colistin were: zero concentrations for E. coli, two concentrations for P. aeruginosa, and one to two concentrations for other nonfermenters. Increases in MICs of tetracycline were: one to five concentrations for all organisms tested. The usual increases in MICs of carbenicillin were: zero concentrations for E. coli and P. aeruginosa and zero to two concentrations for other nonfermenters. These observations indicated that supplementation of Mueller-Hinton broth to contain recommended concentrations of calcium and magnesium had little effect on MICs of aminoglycosides and colistin for E. coli but increased MICs for most nonfermenters, increased MICs of tetracycline for E. coli and all nonfermenters, and had little effect on MICs of carbenicillin for E. coli and P. aeruginosa but increased the MICs for several nonfermenters other than P. aeruginosa.

Campylobacter fetus sepsis with mycotic aortic aneurysm.

Campylobacter fetus is a fastidious, curved, Gram-negative bacillus that has been increasingly associated with human disease. To our knowledge, we are reporting the first documented case of C fetus sepsis associated with an aortic mycotic aneurysm. Typical of previously reported cases of infections caused by this organism, this case involved a debilitated patient who was seen initially with a subacute febrile illness associated with bacteremia, but who died suddenly when the unsuspected aneurysm ruptured. The isolate was presumptively identified by its growth characteristics, motility, curved shape, and the presence of a single polar flagellum.

Rapid identification of nonfermentative gram-negative rods by the Corning N/F system.

A total of 1,298 nonfermentative gram-negative rods were used to evaluate the performance of the individual biochemical tests in the N/F System and to determine whether the observed results included sufficient key reactions for rapid identification. The system included an oxidase test, two screening tubes providing 5 test reactions designed primarily to identify pigment-producing strains of Pseudomonas aeruginosa, and a plate providing 12 test reactions designed to identify other nonfermenters. With both the tubes and plates, most results were consistent with expected conventional test reactions. Use of the tubes permitted the identification of 90% of the strains of P. aeruginosa in 24 h and 97% in 48 h. Use of the plates permitted the identification of 95% of the other oxidative nonfermenters within 24 h and 96% within 48 h. Only 26% of weak and nonoxidative nonfermenters were identified because of the nonreactivity of these organisms in this system. There were no misidentifications based on misleading test results.