Biomedical subjects

D J Hoban

Publications and source records attributed to D J Hoban.

At least 19 recordsLinked to original sources

PubMed2004

In vitro activity of gemifloxacin and contemporary oral antimicrobial agents against 27247 Gram-positive and Gram-negative aerobic isolates: a global surveillance study.

This study was a multi-centre, multi-country surveillance of 27247 Gram-positive and Gram-negative isolates collected from 131 study centres in 44 countries from 1997 to 2000. MICs of gemifloxacin were compared with penicillin, amoxicillin-clavulanic acid, cefuroxime, azithromycin, clarithromycin, trimethoprim-sulphamethoxazole, ciprofloxacin, grepafloxacin and levofloxacin by broth microdilution. Penicillin resistance in Streptococcus pneumoniae was extremely high in the Middle East (65.6%), Africa (64.0%) and Asia (60.4%) and lower in North America (40.3%), Europe (36.9%) and the South Pacific (31.8%). Macrolide resistance in S. pneumoniae was highest in Asia (51.7%) but varied widely between laboratories in Europe (26.0%), North America (21.6%), the Middle East (13.7%), the South Pacific (10.6%) and Africa (10.0%). All the study quinolones were highly active against penicillin-resistant and macrolide-resistant S. pneumoniae. Overall, gemifloxacin had the lowest MIC(90) at 0.06 mg/l with MICs 4-64-fold lower than ciprofloxacin, levofloxacin and grepafloxacin against S. pneumoniae. Gemifloxacin MICs were more potent than grepafloxacin > levoflaxacin > ciproflaxin against the Gram-positive aerobes and shared comparable Gram-negative activity with ciprofloxacin and levofloxacin.

Administration, Oral↗

PubMed2004

Determining incidence of extended spectrum beta-lactamase producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus in 38 centres from 17 countries: the PEARLS study 2001-2002.

The PEARLS study prospectively monitored selected nosocomial pathogens from 38 centres in 13 European, three Middle Eastern countries and South Africa during 2001-2002. Extended spectrum beta-lactamase (ESBL) production rates among Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. were 5.4% (142/2609), 18.2% (401/2,206) and 8.8% (204/2,328), respectively, for all study sites. The overall ESBL production rate for the combined Enterobacteriaceae was 10.5% (747/7,143), highest in Egypt, 38.5%, and Greece, 27.4%, and lowest in The Netherlands, 2.0%, and Germany, 2.6%. IEF, PCR and DNA sequencing determined 10.7% false positives among Enterobacter spp. when using NCCLS guidelines to screen for ESBL production. The prevalence of nosocomial methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium was 32.4% (294/908) and 8.7% (83/949), respectively. PEARLS provides baseline data against which prospective changes in resistant determinants and outcomes can be measured in this ongoing study.

Anti-Bacterial Agents↗

PubMed2004

Designing fluoroquinolone breakpoints for Streptococcus pneumoniae by using genetics instead of pharmacokinetics-pharmacodynamics.

We determined fluoroquinolone microbiological resistance breakpoints for Streptococcus pneumoniae by using genetic instead of pharmacokinetic-pharmacodynamic parameters. The proposed microbiological breakpoints define resistance as the MIC at which >50% of the isolates carry quinolone resistance-determining region mutations and/or, if data are available, when Monte Carlo simulations demonstrate a <90% chance of bacteriological eradication. The proposed microbiological resistant breakpoints are as follows (in micrograms per milliliter): gatifloxacin, >0.25; gemifloxacin, >0.03; levofloxacin, >1; and moxifloxacin, >0.12. Monte Carlo simulations of the once daily 400-mg doses of gatifloxacin and 750-mg doses levofloxacin demonstrated a high level of target attainment (free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio of 30) by using these new genetically derived breakpoints.

Anti-Bacterial Agents↗

PubMed2003

Comparative in vitro surveillance of amoxicillin-clavulanic acid and four oral comparators against 21232 clinical isolates from europe.

The present study was conducted to determine the in vitro activity of amoxicillin-clavulanic acid compared to that of four newer antimicrobial agents (ampicillin, azithromycin, cefuroxime and trimethoprim-sulfamethoxazole). All of the agents were tested against 21232 recent clinical isolates encompassing 37 species submitted from 16 European countries between 1997 and 1999. After 20 years of clinical use, amoxicillin-clavulanic acid continues to retain much of its initial activity against targeted gram-positive organisms, selected gram-negative organisms and major respiratory pathogens.

Administration, Oral↗

PubMed2003

Comparative in vitro potency of amoxycillin-clavulanic acid and four oral agents against recent North American clinical isolates from a global surveillance study.

The in vitro activity of amoxycillin-clavulanic acid was compared with four comparator oral antimicrobial agents; ampicillin, azithromycin, cefuroxime and trimethoprim-sulphamethoxazole against 4536 recent clinical isolates covering 29 species isolated in the US and Canada between 1997 and 1999. Based upon Minimum inhibitory concentrations (MICs), amoxycillin-clavulanic acid was the most active agent against many Gram-positive species and phenotypes including methicillin susceptible Staphylococcus aureus (MSSA) Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae including penicillin intermediate and macrolide resistant strains and was as active as ampicillin against Streptococcus agalactiae, penicillin resistant S. pneumoniae and viridans streptococci. Against Enterobacteriaceae amoxycillin-clavulanic acid in general, displayed weak activity with only Proteus mirabilis and Proteus vulgaris displaying levels of susceptibility above the 90th percentile. Amoxycillin-clavulanic acid had significant activity against many species of Gram-negative non-Enterobacteriaceae including Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis but negligible activity against Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Amoxycillin-clavulanic acid continues to retain excellent activity against the majority of targeted pathogens despite 20 years of clinical use.

Administration, Oral↗

PubMed2002

Prevalence and characterization of macrolide resistance in clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes from North America.

Resistance to macrolides is not a new phenomenon but it deserves attention because of the widespread use of these agents and their inclusion in many clinical guidelines for respiratory tract infections. The most common mechanisms by which Streptococcus pneumoniae and Streptococcus pyogenes develop resistance to macrolides is by target site modification (erythromycin ribosome methylase, erm) and efflux of the drug out of the organisms (macrolide efflux, mef). Target site modification may be of greater concern because it confers high-level resistance to all antimicrobials in the macrolide-lincosamide-streptograminB (MLSB) group. The genotype profiles of macrolide-resistant S. pneumoniae and S. pyogenes differ somewhat across regions in the US and between the US and Canada and other countries. There is some evidence for an association between macrolide resistance and treatment failure but this must be researched more fully. S. pneumoniae and S. pyogenes isolates resistant to macrolides are generally susceptible to ketolide antimicrobials because these agents bind more strongly to the relevant domain of the ribosomal subunit (withstanding erm resistance) and are less vulnerable to efflux compared to the macrolides.

Anti-Bacterial Agents↗

PubMed2001

Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997-1999.

The in vitro activities of numerous antimicrobials against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from patients with bloodstream and respiratory tract infections in the United States, Canada, Europe, Latin America, and the Asia-Pacific region were studied in the SENTRY Antimicrobial Surveillance Program. Penicillin resistance (minimum inhibitory concentration, > or =2 microg/mL) was noted in all 5 geographic regions, and a high and increasing rate of macrolide resistance among S. pneumoniae isolates was observed. Elevated rates of resistance to clindamycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline were seen. beta-Lactamase-mediated resistance in H. influenzae to amoxicillin and variable trimethoprim-sulfamethoxazole resistance by region were documented. Resistance to several drugs continues to emerge among pneumococci worldwide, but more stable resistance patterns have been noted for H. influenzae and M. catarrhalis. Continued surveillance of this pathogen group appears to be prudent.

Anti-Bacterial Agents↗

PubMed2001

Antibiotic susceptibilities among recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis from fifteen countries.

Between July 1998 and July 1999, 3,060 Haemophilus influenzae and 1,486 Moraxella catarrhalis strains were isolated in 31 centers in 15 countries in order to determine their antimicrobial susceptibilities and the presence of beta-lactamase production in Haemophilus influenzae. Overall 17.1% of the Haemophilus influenzae isolates were beta-lactamase positive, while more than 95% were susceptible to amoxicillin/clavulanate, cefaclor, loracarbef, cefuroxime, azithromycin and ciprofloxacin. Eleven (0.3%) isolates were beta-lactamase positive and ampicillin resistant and 7 (0.2%) isolates were ciprofloxacin resistant. The minimum inhibitory concentrations for 90% of the isolates tested were lowest for ciprofloxacin (0.03) and highest for cefprozil (8) against Moraxella catarrhalis.

Anti-Bacterial Agents↗

PubMed2001

Comparative in vitro potency of gemifloxacin and fluoroquinolones against recent European clinical isolates from a global surveillance study.

Gemifloxacin, a new fluoroquinolone with enhanced activity against gram-positive aerobes, was compared to ciprofloxacin, levofloxacin and ofloxacin against 21,464 recent isolates from 16 European countries. Gemifloxacin was the most potent fluoroquinolone against streptococci including penicillin-, macrolide- and ciprofloxacin-resistant Streptococcus pneumoniae, Staphylococcus aureus, coagulase-negative staphylococci, Acinetobacter spp., Haemophilus spp. and Moraxella catarrhalis. This drug was more potent than or comparable to ciprofloxacin against members of the family Enterobacteriaceae, Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Gemifloxacin is a promising fluoroquinolone with potent in vitro activity.

Anti-Infective Agents↗

PubMed2001

Antimicrobial susceptibilities of clinical isolates of Haemophilus influenzae and Moraxella catarrhalis collected during 1999-2000 from 13 countries.

OBJECTIVE: To determine antimicrobial activity against Haemophilus influenzae and Moraxella catarrhalis. METHODS: A central laboratory performed NCCLS susceptibility testing for all isolates and beta-lactamase and capsular serotype determinations for H. influenzae. RESULTS: A total of 2712 H. influenzae and 1079 M. catarrhalis were collected. H. influenzae susceptibilities were >90% for amoxicillin/clavulanate, cefaclor, loracarbef, cefprozil, cefuroxime, ciprofloxacin, azithromycin and clarithromycin and were <80% for trimethoprim/sulfamethoxazole and ampicillin. 19.3% were beta-lactamase positive. The most common serotype was type-b (5.6%); 86.1% were nontypeable. M. catarrhalis had MIC90 within therapeutic range for all antimicrobials except ampicillin. CONCLUSION: The conclusion of the study is that antimicrobials, except ampicillin and trimethoprim/sulfamethoxazole, remain good empiric choices against H. influenzae and M. catarrhalis.

Adolescent↗

PubMed2001

In vitro pharmacodynamic modelling simulating free serum concentrations of fluoroquinolones against multidrug-resistant Streptococcus pneumoniae.

An in vitro pharmacodynamic model was used to compare bacterial killing and the development of resistant mutants in the presence of respiratory fluoroquinolones and ciprofloxacin. Free (protein unbound) serum concentrations were simulated using peak serum concentrations and AUC(24), achieved after standard oral doses for treatment of community-acquired respiratory infections. Respiratory fluoroquinolones reduced the inoculum of isolates of multidrug-resistant Streptococcus pneumoniae below the level of detection in the model at 12 h and did not allow regrowth to occur over 48 h. In contrast, ciprofloxacin had a bacteriostatic (<3 log(10) reduction of the initial inoculum) effect, with rapid regrowth occurring over 48 h. Bacterial regrowth and the development of resistant mutants did not occur with any of the respiratory fluoroquinolones. Rapid regrowth and the development of resistant mutants, with MICs two- to eight-fold higher than the MIC before treatment, occurred with ciprofloxacin. These data suggest that the new respiratory fluoroquinolones with a free AUC(24)/MIC of 35-63 reduce the inoculum of multidrug-resistant S. pneumoniae below the level of detection without regrowth or development of resistance over 48 h. This study also demonstrated the poor activity of ciprofloxacin against S. pneumoniae.

Administration, Oral↗

PubMed2001

Nitrofurantoin is active against vancomycin-resistant enterococci.

The activity of nitrofurantoin was tested against 300 isolates of Enterococcus faecium, Enterococcus faecalis, and Enterococcus gallinarum. No isolates tested were resistant to nitrofurantoin (MIC, >/=128 microg/ml), including vancomycin-resistant E. faecium isolates with vanA- and vanB-positive genotypes and vancomycin-resistant E. gallinarum isolates. We conclude that nitrofurantoin may provide effective treatment of urinary tract infections caused by vancomycin-resistant enterococci.

Anti-Bacterial Agents↗

PubMed2001

Influence of human serum on antifungal pharmacodynamics with Candida albicans.

Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum-20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (> or = 4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding.

Antifungal Agents↗

PubMed2001

Macrolide-resistant Streptococcus pneumoniae in Canada during 1998-1999: prevalence of mef(A) and erm(B) and susceptibilities to ketolides.

In this study (1998-1999), we collected 215 macrolide-resistant Streptococcus pneumoniae isolates from an ongoing Canadian Respiratory Organism Surveillance Study involving 23 centers representing all regions of Canada. The prevalence of erythromycin-resistant S. pneumoniae was 8% (215 of 2,688). Of the 215 isolates, 48.8% (105 of 215) were PCR positive for mef(A) and 46.5% (100 of 215) were PCR positive for erm(B). The ketolides telithromycin and ABT-773 demonstrated excellent activity against both mef(A) (MIC for 90% of strains [MIC(90)], 0.06 and 0.03 microg/ml, respectively) and erm(B) (MIC(90), 0.06 and 0.03 microg/ml, respectively) strains of S. pneumoniae.

Anti-Bacterial Agents↗

PubMed2001

Review of macrolides and ketolides: focus on respiratory tract infections.

The first macrolide, erythromycin A, demonstrated broad-spectrum antimicrobial activity and was used primarily for respiratory and skin and soft tissue infections. Newer 14-, 15- and 16-membered ring macrolides such as clarithromycin and the azalide, azithromycin, have been developed to address the limitations of erythromycin. The main structural component of the macrolides is a large lactone ring that varies in size from 12 to 16 atoms. A new group of 14-membered macrolides known as the ketolides have recently been developed which have a 3-keto in place of the L-cladinose moiety. Macrolides reversibly bind to the 23S rRNA and thus, inhibit protein synthesis by blocking elongation. The ketolides have also been reported to bind to 23S rRNA and their mechanism of action is similar to that of macrolides. Macrolide resistance mechanisms include target site alteration, alteration in antibiotic transport and modification of the antibiotic. The macrolides and ketolides exhibit good activity against gram-positive aerobes and some gram-negative aerobes. Ketolides have excellent activity versus macrolide-resistant Streptococcus spp. Including mefA and ermB producing Streptococcus pneumoniae. The newer macrolides, such as azithromycin and clarithromycin, and the ketolides exhibit greater activity against Haemophilus influenzae than erythromycin. The bioavailability of macrolides ranges from 25 to 85%, with corresponding serum concentrations ranging from 0.4 to 12 mg/L and area under the concentration-time curves from 3 to 115 mg/L x h. Half-lives range from short for erythromycin to medium for clarithromycin, roxithromycin and ketolides, to very long for dirithromycin and azithromycin. All of these agents display large volumes of distribution with excellent uptake into respiratory tissues and fluids relative to serum. The majority of the agents are hepatically metabolised and excretion in the urine is limited, with the exception of clarithromycin. Clinical trials involving the macrolides are available for various respiratory infections. In general, macrolides are the preferred treatment for community-acquired pneumonia and alternative treatment for other respiratory infections. These agents are frequently used in patients with penicillin allergies. The macrolides are well-tolerated agents. Macrolides are divided into 3 groups for likely occurrence of drug-drug interactions: group 1 (e.g. erythromycin) are frequently involved, group 2 (e.g. clarithromycin, roxithromycin) are less commonly involved, whereas drug interactions have not been described for group 3 (e.g. azithromycin, dirithromycin). Few pharmacoeconomic studies involving macrolides are presently available. The ketolides are being developed in an attempt to address the increasingly prevalent problems of macrolide-resistant and multiresistant organisms.

Adolescent↗

PubMed2000

In vitro activity of selected cephalosporins and erythromycin against staphylococci and pneumococci isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

The SENTRY Antimicrobial Surveillance Program employs a worldwide network of hospitals to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with nosocomial and community-acquired bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY data is to extract information on the current North American susceptibility patterns of pneumococci and oxacillin-susceptible staphylococci from the comprehensive SENTRY program database. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of 34 530 North American bacterial isolates tested during 1997 and 1998, 565 (1.6%) were oxacillin-susceptible, coagulase-negative staphylococci (CoNS). Cefazolin, cefepime, and ceftriaxone all had excellent activity against these CoNS (97.3%-99. 3% susceptible), and 90.4% were susceptible to ceftazidime. A total of 4404 isolates (12.8%) were oxacillin-susceptible Staphylococcus aureus. Overall, 98.9% to 99.2% were susceptible to cefazolin, cefepime, and ceftriaxone; ceftazidime did not have acceptable activity against these S. aureus. Streptococcus pneumoniae accounted for 1665 (4.8%) of North American SENTRY isolates. A total of 1212 isolates (72.8%) were fully susceptible to penicillin (MIC </= 0.06 microg/ml), 250 (15%) were penicillin intermediate (MIC 0.12-1 microg/ml), and 203 (12.2%) were penicillin resistant (MIC >/= 2 microg/ml). The rate of penicillin susceptibility was highest in Canada, and lowest in the South Central and South East regions of the United States. Cefepime, cefuroxime, ceftazidime, and erythromycin all demonstrated excellent efficacy (94%-99.8% susceptibility) against fully penicillin-susceptible isolates of S. pneumoniae. Among pneumococci with intermediate penicillin resistance, 88% were susceptible to cefepime, 92% to cefotaxime, and only 14% to ceftazidime. None of the antimicrobial agents in this analysis demonstrated adequate activity against fully penicillin-resistant pneumococci. In summary, the fourth-generation cephalosporin, cefepime, demonstrated consistently excellent efficacy against oxacillin-susceptible staphylococci and most pneumococci, and remains an appropriate choice for empiric therapy of serious infections.

Anti-Bacterial Agents↗

PubMed2000

Comparison of the activity of two broad-spectrum cephalosporins tested against 2,299 strains of Pseudomonas aeruginosa isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

Pseudomonas aeruginosa is an important nosocomial pathogen. Resistance to certain beta-lactam antimicrobial agents among P. aeruginosa is increasing. The SENTRY Antimicrobial Surveillance Program was designed to employ a network of hospitals in the United States, Canada, Latin America, and Europe to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY results was to extract information on the current North American susceptibility pattern of P. aeruginosa for two antipseudomonal cephalosporins, ceftazidime, and cefepime. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory by using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of the 34, 530 North American bacterial isolates tested during 1997 and 1998, 2299 (6.7%) were P. aeruginosa. There were no substantial differences in regional rates of P. aeruginosa susceptibility to ceftazidime (range 78.8-81.9%) or cefepime (range 80.0-83.4%) The percentage of resistant isolates among the 1784 United States isolates was 13.3% for ceftazidime versus 7.1% for cefepime (p < 0.05). It is essential to continue surveillance of the in vitro efficacy of these and other beta-lactam agents against P. aeruginosa because of the clinical importance of these safe and broad-spectrum cephems used alone or in combination in current clinical practice.

Cefepime↗

PubMed2000

In vitro efficacy of six cephalosporins tested against Enterobacteriaceae isolated at 38 North American medical centres participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

The SENTRY Antimicrobial Surveillance Program is an ongoing international collaboration that monitors the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial infections. SENTRY data on the current cephalosporin susceptibility patterns (1997-98) of North American isolates of clinically important Enterobacteriaceae were analyzed. Susceptibility to a selection of cephalosporins was assessed at a central laboratory using reference broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. The third- and fourth-generation cephalosporins tested demonstrated excellent activity against Escherichia coli and Klebsiella pneumoniae, whereas some of the older agents maintained good efficacy. Extended spectrum beta-lactamases were detected in all regions of the United States and Canada (1.8-10.7%). Cefepime was the most active agent tested against pathogens with the potential for enzyme-mediated resistance due to Amp C. The third-generation agents maintained acceptable efficacy against Serratia marcescens, but were less effective against Citrobacter and Enterobacter species. The older cephalosporins were generally inadequate against these pathogens, in contrast to cefepime, which was the widest spectrum cephalosporin overall. Some significant regional variations in spectrum were detected.

Cefepime↗