M. E. Erwin

The prevalence of fluoroquinolone resistance among clinically significant respiratory tract isolates of Streptococcus pneumoniae in the United States and Canada—1997 results from the SENTRY Antimicrobial Surveillance Program

As part of the SENTRY antimicrobial resistance surveillance program, a total of 1100 clinically significant respiratory tract isolates of Streptococcus pneumoniae were tested for susceptibility to six fluoroquinolone antimicrobial agents: ciprofloxacin, levofloxacin, gatifloxacin, grepafloxacin, sparfloxacin, and trovafloxacin. Isolates were obtained during the 5-month period, February to June, 1997 from 27 United States medical center laboratories and seven laboratories in Canadian health care institutions. All testing was performed in a single center. Of 1100 test strains, 3 (0.3%), all from different U.S. centers, were fluoroquinolone resistant. Among the remaining 1097 fluoroquinolone-susceptible isolates, the rank order of activity among the six agents tested in this study was grepafloxacin (modal MIC = 0.25 microgram/mL) = trovafloxacin (modal MIC = 0.25 microgram/mL) = sparfloxacin (0.25 microgram/mL) > gatifloxacin (0.5 microgram/mL) > levofloxacin (1 microgram/mL) = ciprofloxacin (1 microgram/mL). Fluoroquinolone resistance is currently uncommon among respiratory tract isolates of S. pneumoniae in North America, but there exist clear differences between the in vitro activities of different fluoroquinolones for this organism.

Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines

SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthyridone that has a broad spectrum of activity, especially against Gram-positive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxacin, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp. isolated recently from more than 30 medical centers in North and South America. These included 70 isolates with decreased susceptibility to recently released fluoroquinolones (levofloxacin MIC, > or = 4 micrograms/mL). All strains were tested by reference microdilution methods in lysed horse blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 beta-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptococcus pneumoniae were resistant to penicillin, respectively. SB-265805 potency against 301 pneumococci (MIC90, 0.06 microgram/mL) was fourfold more active than moxifloxacin and was > or = eightfold more potent than other quinolones. Against beta-haemolytic streptococci, SB-265805 and moxifloxacin were the most active (MIC90, 0.06 and 0.25 microgram/mL, respectively), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 microgram/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 microgram/mL) were fourfold lower than sparfloxacin or grepafloxacin, and twofold more active than moxifloxacin. A nine-laboratory quality control (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a modal SB-265805 MIC of 0.016 microgram/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 microgram/mL). The SB-265805 disk (5-microgram) QC range was 28-34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activity against Streptococcus species was superior to sparfloxacin, grepafloxacin, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug for its potential human clinical application against streptococcal infections.

In vitro activity of OPC-17116 compared to other broad-spectrum fluoroquinolones

The in vitro activity of OPC-17116 was compared to that of five similar fluoroquinolones (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and temafloxacin). A total of 700 isolates from recent cases of clinical bacteremia were tested. Fifty additional stock strains with well-characterized resistance mechanisms were also processed. The minimal concentrations inhibiting 90 % of strains (MIC90) ofEnterobacteriaceae species were for OPC-17116 0.015–0.5 µg/ml and for ciprofloxacin 0.015–0.25 µg/ml.Moraxella catarrhalis, Haemophilus influenzae andNeisseria gonorrhoeae were very susceptible to OPC-17116 (MIC90 0.015 µg/ml) thus being fourfold more active than ciprofloxacin. For all β-hemolytic streptococci and pneumococci OPC-17116 MICs were ≤0.5 µg/ml. The most resistant enteric bacilli were among theCitrobacter freundii andProvidencia rettgeri strains (MIC90 0.5 µg/ml).Pseudomonas aeruginosa strains were comparably susceptible to OPC-17116 (MIC90 0.5 µg/ml). Low pH and CO2 incubation had an adverse effect on OPC-17116 MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas and someEnterobacteriaceae.

Antimicrobial activity of ten macrolide, linsosamine and streptogramin drugs tested againstLegionella species

RP59500, a semisynthetic pristinamycin combination, and 14 other antimicrobial agents were tested against 108Legionella strains. Of the ten macrolide, lincosamine and streptogramin agents tested, the new streptogramin RP59500 ranked seventh in order of activity againstLegionella pneumophila on the basis of MIC90 results as follows: clarithromycin = 14-OH clarithromycin (MIC90 0.12 mg/l) > roxithromycin > erythromycin = tylosin = virginiamycin > RP59500 (MIC90 1 mg/l) = azithromycin > dirithromycin > clindamycin (MIC90 8 mg/l). Of all 14 drugs tested in this study, rifampicin was the most potent with an MIC90 of 0.008 mg/l. In this retrospective study ofLegionella strains (1981–1990 isolates), we observed no trend toward resistance to the agents investigated.

Antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) against over 100 Legionella sp. isolates.

The antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) were compared with those of five similar compounds and four comparison drugs against 103 strains of Legionella pneumophila and five other Legionella species type strains. When concentrations inhibiting 90% of strains tested (MIC90s) for L. pneumophila were determined, CI-960 and temafloxacin emerged as the most active (0.015 microgram/ml) and were followed in potency by E4695 (0.03 microgram/ml). This activity was two- to fourfold greater than that of the reference drug, ciprofloxacin, and approached that of rifampin (MIC90, 0.008 microgram/ml). All fluoroquinolones studied were more active than erythromycin (MIC90, 0.5 microgram/ml). These two investigational fluoroquinolones appear well suited for further in vivo study of legionellosis therapy.

Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina

OBJECTIVES 1) To evaluate the antimicrobial susceptibility pattern of vancomycin-resistant enterococci to the antimicrobial agents that are commonly used to treat enterococci infections and to some alternative drugs. 2) To evaluate the accuracy of E test for susceptibility testing enterococci. MATERIAL AND METHOD We evaluated 87 clinical VRE isolates that were selected from a previous study which analyzed 1936 clinical isolates collected and processed in 97 US medical centers in the last quarter of 1992. The isolates were identified to the species level by using the API 20S System, the Vitek gram-positive identification cards and a modified version of the conventional method proposed by Facklam and Collins. The in vitro susceptibility testing was performed by broth microdilution, E test and disk diffusion methods, following the criteria described by the National Committee for Clinical Laboratory Standards (NCCLS). The VRE isolates were tested against antimicrobial agents commonly used to treat enterococci infections (vancomycin, teicoplanin, ampicillin, penicillin, gentamicin and streptomycin) and against ten potential alternative drugs (chloramphenicol, doxycycline, sparfloxacin, ciprofloxacin, clinafloxacin, erythromycin, spectinomycin, trospectomycin, trimetoprim-sulfametoxazol and novobiocin). RESULTS Our results showed a high rate of resistance to ampicillin and penicillin (86%). High level resistance to gentamicin and streptomycin was demonstrated by 82% and 85% respectively. Although teicoplanin and vancomycin belong to the same antibiotic group (glycopeptide), 29% of VRE were susceptible to teicoplanin. Among the alternative drugs, trospectomycin, doxycyclin and chloramphenicol showed the highest in vitro activity, with 94%, 92% and 82% susceptibility respectively. In addition, erythromycin, trimetoprim-sulfametoxazol and ciprofloxacin showed the highest rates of resistance (98%, 83% and 69%, respectively). CONCLUSION The treatment options for infections caused by vancomycin-resistant enterococci seem to be very narrow since a small percentage of those isolates were susceptible to the other antimicrobial agents commonly used to treat these infections and only a few of the alternative drugs tested showed good in vitro activity. Many regimens using various antibiotic combinations have been tested against VRE, most of them with fluoroquinolones. However further studies are necessary to evaluate the clinical role of these antibiotic combinations.OBJETIVOS. 1) Avaliar o padrao de sensibilidade in vitro de amostras clinicas de enterococos resistentes a vancomicina (ERV), aos antimicrobianos comumente utilizados no seu tratamento, bem como a antimicrobianos alternativos. 2) Avaliar a acuracia do E test, em comparacao aos outros testes de sensibilidade a antimicrobianos (microdiluicao em caldo e difusao em disco). MATERIAL E METODOS. Foram analisadas 87 amostras clinicas de ERVs selecionadas de 1.936 isolados de enterococos coletados em 97 hospitais norte-americanos, no ultimo trimestre de 1992. A identificacao em nivel de especie foi feita pelos sistemas API 20S, Vitek e uma versao modificada do metodo convencional proposto por Facklam e Collins. A avaliacao da sensibilidade in vitro aos antimicrobianos foi realizada pela tecnica de microdiluicao em caldo, E test e metodos de difusao em disco. As amostras foram testadas, tanto para antimicrobianos normalmente utilizados no tratamento de infeccoes enterococicas (vancomicina, teicoplanina, ampicilina, penicilina, gentamicina e estreptomicina), como tambem para drogas alternativas potencialmente uteis (cloranfenicol, doxiciclina, esparfloxacina, ciprofloxacina, clinafloxacina, eritromicina, espectinomicina, trospectomicina, trimetoprim-sulfametoxazol e novobiocina). RESULTADOS. A avaliacao dos testes de sensibilidade das 87 amostras de ERV revelou resistencia, a ampicilina em torno de 86%, o mesmo sendo observado para penicilina. Em relacao aos aminoglicosideos, obtivemos alto grau de resistencia, em torno de 82% e 85%, para gentamicina e estreptomicina, respectivamente. Apesar de pertencer a mesma classe da vancomicina, a teicoplanina foi ativa contra 29% das amostras de ERV. Entre os antimicrobianos alternativos testados, os que apresentaram maiores taxas de sensibilidade foram o cloranfenicol, a doxiciclina e a trospectomicina (82%, 92% e 94% de isolados suscetiveis, respectivamente). CONCLUSAO. O tratamento de infeccoes causadas por enterococos multirresistentes ainda e um desafio, e varios esquemas ja vem sendo propostos na literatura. Sao necessarios, no entanto, mais trabalhos analisando a efetividade clinica dessas combinacoes de antibioticos antes que recomendacoes definitivas possam ser feitas.

False resistance results using 5 µg cefixime disks to testHaemophilus influenzae

1. Bellini M,I, Peel RN, Teny RM: Chlamydia: its influence in chronic secretory otitis media. Journal of Laryngology and Otology 1988, 102: 673-676. 2. Barnes RC: Laboratory diagnosis of human chlamydial infections. Clinical Microbiology Reviews 1989, 2: 119136. 3. Watanakunaknru C, Levy DH: Pharyngitis and urethritis due to Chlamydia trachomatis. Journal of hffectious Diseases 1983, 147: 364. 4. San Joaquin VH, Rettig P J: Role of Chlamydia trachomatis in upper-respiratory-tract infections in children. Journal of Infectious Diseases 1986, 154: 193. 5. Grayston JT, Wang SP, Kuo CC, Campell LA: Current knowledge on Chlamydia pneumoniae, strain TWAR, an important cause of pneumonia and other acute respiratory diseases. European Journal of Clinical Microbiology and Infectious Diseases 1989, 8: 191-202.

In vitro activity of E-4868, a new trifluoroquinolone, compared to six similar compounds.

The compound E-4868 (Laboratorios Dr. Esteve) is a trifluoro, 7-azetidinyl quinolone with properties resembling those of other fluoroquinolones. Its activity in vitro was compared to that of six other similar drugs against more than 700 nosocomial isolates using standard methods. The MIC50s of E-4868 for enteric bacilli ranged from 0.015 to 0.25 µg/ml, being highest forProvidencia spp.Pseudomonas aeruginosa strains were two-fold more susceptible to E-4868 than to ofloxacin. MICs of E-4868 forHaemophilus influenzae, Moraxella catarrhalis and pathogenicNeisseria spp. were all ≤ 0.12 µg/ml. E-4868 was equal in activity to or eight-fold more active than ciprofloxacin against gram-positive cocci. The MICs of E-4868 for pneumococci were all ≤ 0.5 µg/ml but anaerobes such asBacteroides fragilis were generally less susceptible (MIC90, 4 µg/ml). There was almost complete cross-resistance to several other fluoroquinolones. Resistant mutants were selected by a multiple passage technique but the rate of mutation to resistance was very low (< 10−8) at an 8 x MIC.

Gatifloxacin Susceptibility Testing Interpretive Criteria and Quality Control Guidelines for Dilution and Disk Diffusion Methods

Gatifloxacin (formerly AM-1155 or CG5501) is a newer 8-methoxy fluoroquinolone with a wide spectrum of antimicrobial activity.[1-4] Among the species inhibited by gatifloxacin are selected anaerobes, Chlamydia spp., Mycoplasma pneumoniae, mycobacteria, drug-resistant Streptococcus pneumoniae andNeisseria gonorrhoeae as well as many nonfastidious, rapid-growing bacteria. Gatifloxacin has excellent bioavailability, with an elimination half-life of 7 to 8 hours and peak serum concentrations of 3.35 and 5.41 mg/L, respectively, with single 400 and 600mg doses.[5] It penetrates macrophages and will concentrate 5to 7-fold within the cell. The drug was well tolerated and the intake of food had no adverse effect on the pharmacokinetic features, which allowed advancement to human clinical trials. The risk of phototoxicity was also considered low. In this study, we report the results of testing the activity of gatifloxacin against rapidly growing aerobic pathogens by 2 methods published by the National Committee for Clinical Laboratory Standards (NCCLS) to determine interpretive criteria for antimicrobial susceptibility testing.[6,7] In addition, the quality control guidelines were established for the gatifloxacin 5μg disks and broth microdilution tests by use of a 9-laboratory trial conforming to NCCLS study design.[8]

Antimicrobial Activity of Gatifloxacin Against Campylobacter jejuni and Anaerobic Bacteria

Campylobacter jejuni, a Gram-negative microaerophilic organism, has emerged as an important pathogen which can cause a variety of diseases, including severe gastroenteritis, septic arthritis, meningitis and bacteraemia, and has also been associated with Guillain-Barré syndrome.[1] It is estimated that more than 2 million infections per year are caused by this organism, an incidence greater than that attributed to Salmonella and Shigella combined.[1] The traditional and effective treatment regimen for C. jejuni infections has been erythromycin. Tetracycline and the fluoroquinolone ciprofloxacin have also been frequently prescribed. However, resistance rates to ciprofloxacin (50 to 81.6%), tetracycline (60%) and erythromycin (12.6%) among C. jejuni strains have been documented. As antimicrobial resistance increases among C. jejuni isolates, the need for alternative antimicrobial agents becomes critical. Gatifloxacin is a fluoroquinolone with antimicrobial properties similar to those of other newer drugs in its class. This compound has previously been shown to inhibit many Gram-positive and Gram-negative organisms including anaerobic species.[2] In this study, the antimicrobial activity of gatifloxacin against C. jejuni isolates from the US and Mexico was compared with that of 8 other antimicrobials by Etest,[3] as well as similar studies with strict anaerobic bacteria from patients in the US.We also compared the Etest and the reference agar dilution susceptibility testing[4,5]results to determine the ability of the stable-gradient test to detect antimicrobial resistance to gatifloxacin and other agents. Cross resistance between ciprofloxacin, gatifloxacin, levofloxacin and trovafloxacin was also examined. Materials and Methods