Biomedical subjects

Stephen G Jenkins

Publications and source records attributed to Stephen G Jenkins.

12 recordsLinked to original sources

PubMed2006

Prevalence and antibacterial susceptibility of mef(A)-positive macrolide-resistant Streptococcus pneumoniae over 4 years (2000 to 2004) of the PROTEKT US Study.

In the United States, approximately 30% of Streptococcus pneumoniae isolates are macrolide (erythromycin [ERY]) resistant (ERSP), most commonly due to expression of the mef(A) gene previously associated with lower-level ERY resistance (ERYr; MIC=1 to 4 microg/ml). The data from the PROTEKT US surveillance study were analyzed to evaluate the prevalence and antibacterial susceptibility of mef(A)-positive ERSP. In all, 26,634 isolates of S. pneumoniae were collected in the United States between 2000 and 2004 from centers common to all years. ERYr was stable at approximately 29% over the 4 years, but the proportion of ERSP isolates positive for mef(A) alone decreased (year 1 [2000 to 2001], 69.0%; year 4 [2003 to 2004], 60.7%), with the sharpest declines seen in isolates from patients from 0 to 2 years of age. Conversely, the proportion isolates positive for both erm(B) and mef(A) increased over the duration of the present study (year 1, 9.3%; year 4, 19.1%), a change that was again most marked in patients aged <or=2 years. The majority of ERSP isolates expressing mef(A) alone exhibited higher than previously reported levels of ERYr (MIC90=16 microg/ml). However, the ketolide antibacterial telithromycin consistently demonstrated in vitro activity against these isolates over the 4 years of the study (MIC90=0.5 to 1 microg/ml).

Anti-Bacterial Agents↗

PubMed2006

Rhinosinusitis: developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗

PubMed2006

Stage of change behavioral assessment tool fails to predict the prevalence of chlamydia in an urban adolescent health clinic.

STUDY OBJECTIVE: Strategies to reduce STI among adolescents and young adults have failed to consistently demonstrate effectiveness. A universal approach may not be appropriate because individuals are at different stages with respect to self-management behaviors. Thus, the Stage of Change Transtheoretical Model has been advocated. This study was conducted to determine whether staging could be accomplished in an urban adolescent clinic and whether it provides a tool to predict STI risk. DESIGN: Participants were interviewed and staged according to a standardized instrument with respect to sexual risk behaviors and contraceptive use. SETTING: Urban adolescent health clinic. PARTICIPANTS: 103 females (ages 18-24). INTERVENTIONS: A physical examination and diagnostic tests for syphilis, HSV, HCV, chlamydia, gonorrhea and HPV were performed. MAIN OUTCOME MEASURES: Stages for behaviors to reduce STI risk and to utilize contraception and STI prevalence. RESULTS: 78% of the participants were in the three earliest stages of behavior (precontemplative, contemplative, and ready for action) with respect to condom use for STI prevention; conversely only 47% were in early stages with respect to birth control practices. Of the participants tested, 12/81 (15%) had chlamydial infection detected by molecular techniques, whereas no participants had gonorrhoeae. Among the subset tested for HPV DNA, 18/45 (40%) were positive. The diagnostic behavior stage for STI prevention did not correlate with the presence of chlamydia. CONCLUSIONS: A staging instrument can be implemented into adolescent health clinic practice, but cannot be used as a risk assessment tool for the presence of chlamydia. Additionally females are more likely to protect themselves against pregnancy than against an STI.

Adolescent↗

PubMed2006

Rhinosinusitis: Developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗

PubMed2005

Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in the USA, 2000-2003: PROTEKT US years 1-3.

OBJECTIVES: To determine geographic and temporal trends in anti-bacterial resistance among Streptococcus pneumoniae isolated from patients with respiratory tract infections as part of the PROTEKT US surveillance study (2000-2003). METHODS: From 2000 to 2003, 31 001 isolates of S. pneumoniae were collected. Anti-bacterial minimum inhibitory concentrations were determined at a central laboratory using the CLSI broth microdilution method. Macrolide resistance genotypes were determined by PCR. RESULTS: Overall, 29.4, 22.5, 0.9, and 0.02% of S. pneumoniae isolates were resistant to erythromycin, penicillin, levofloxacin, and telithromycin, respectively, with considerable regional variability. Multidrug resistance was stable at approx. 31%. Among macrolide-resistant isolates, mef(A) was the most prevalent resistance gene identified; however, the percentage of isolates with this gene decreased from 68.8% (2000) to 63.9% (2003), while the prevalence of isolates containing both the erm(B) and mef(A) genes increased (2000, 9.7%; 2003, 16.4%). Over 90% of these erm(B)+mef(A)-positive isolates were also resistant to penicillin, tetracycline, or trimethoprim-sulfamethoxazole, while 98.6% were susceptible to levofloxacin and 99.1% were susceptible to telithromycin. CONCLUSIONS: Penicillin and erythromycin resistance among isolates of S. pneumoniae from the U.S.A. remained high over the 3 years of the study. Telithromycin demonstrated potent in vitro activity against pneumococcal strains.

Adolescent↗

PubMed2005

Pharmacodynamic analysis of the microbiological efficacy of telithromycin in patients with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Telithromycin, a ketolide antibacterial, demonstrates concentration-dependent bactericidal activity against the major pathogens causing community-acquired respiratory tract infections. The objective of this study was to explore the relationships between pharmacokinetic/pharmacodynamic predictor variables, such as area under the plasma concentration-time curve (AUC) over minimum inhibitory concentration (MIC) [AUC/MIC], maximum plasma concentration (C(max)) over MIC (C(max)/MIC) and microbiological outcome from telithromycin therapy for community-acquired pneumonia (CAP). PATIENTS AND METHODS: Data were pooled from five phase III studies of oral telithromycin (800 mg once daily for 7-10 days) for the outpatient treatment of adults with CAP. Only subjects with a single pathogen isolated at baseline, a telithromycin MIC determination and at least one plasma pharmacokinetic sample were included. Bacteriologically modified intent-to-treat (bmITT) and bacteriologically evaluable per protocol (PPb) populations were analysed. Individual AUC and C(max) Bayesian estimates were obtained with a population pharmacokinetic model. Logistic regression, nonparametric smoothing, and classification analysis and regression tree (CART) were used to assess the relationship between AUC/MIC and C(max)/MIC and microbiological outcome by pathogen. RESULTS: The bmITT population included 224 patients (Streptococcus pneumoniae in 113, Haemophilus influenzae in 89 and Staphylococcus aureus in 22). Median telithromycin MIC was 0.015 microg/mL for S. pneumoniae, 2.0 microg/mL for H. influenzae and 0.12 microg/mL for S. aureus, with median AUC/MIC of 907.1, 6.9 and 98.4, and median C(max)/MIC of 172.0, 1.3 and 20.4 for the three pathogens, respectively. Both logistic regression and nonparametric smoothing showed the probability of microbiological cure to be consistently greater than 90% over the observed range of predictor variables. No reliable AUC/MIC or C(max)/MIC breakpoints were identified by CART. CONCLUSION: Telithromycin exhibits near-maximal efficacy against three major pathogens causing CAP at a dose of 800 mg once daily.

Adolescent↗

PubMed2005

Emergence and spread of Streptococcus pneumoniae with erm(B) and mef(A) resistance.

Streptococcus pneumoniae isolates (N = 31,001) were collected from patients with community-acquired respiratory tract infections during the PROTEKT US surveillance study (2000-2003). While the macrolide (erythromycin) resistance rate remained stable at approximately 29%, the prevalence of resistant isolates containing both erm(B) and mef(A) increased from 9.7% in year 1 to 16.4% in year 3, with substantial regional variability. Almost all (99.2%) dual erm(B) + mef(A) macrolide-resistant isolates exhibited multidrug resistance, whereas 98.6% and 99.0% were levofloxacin- and telithromycin-susceptible, respectively. These strains were most commonly isolated from the ear or middle-ear fluid of children. Of 152 representative erm(B)+mef(A) isolates, >90% were clonally related to the multidrug-resistant international Taiwan19F-14 clonal complex 271 (CC271). Of 366 erm(B)+mef(A) isolates from the PROTEKT global study (1999-2003), 83.3% were CC271, with the highest prevalence seen in South Africa, South Korea, and the United States. This study confirms the increasing global emergence and rapidly increasing US prevalence of this multidrug-resistant pneumococcal clone.

Adolescent↗

PubMed2004

Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus.

OBJECTIVES: Linezolid resistance in rare isolates of Staphylococcus aureus has been associated with G2576T mutations in domain V of the 23S rRNA gene. We report the analysis of a clinical S. aureus isolate that developed linezolid resistance (MIC of linezolid of 12 mg/L) after a 25 day course of the drug. Sequencing identified G2576T mutations in four of the five copies of the 23S rRNA gene. METHODS: To examine the stability of this resistance, we serially passaged this original isolate 60 times over a 75 day period on antimicrobial-free medium. RESULTS: After 30 passages, the MIC of linezolid had decreased to 8 mg/L and only two of the five copies of the 23S rRNA gene contained the G2576T mutation. After 60 passages, the MIC of linezolid fell to 2 mg/L and only one of the five 23S rRNA gene copies contained the mutation. The original and two passaged staphylococci were indistinguishable by pulsed-field gel electrophoresis. CONCLUSIONS: In the absence of antibiotic pressure, linezolid resistance was unstable in a clinical isolate that did not have all copies of the 23S rRNA gene mutated, although a single copy of mutant rDNA was maintained. Gene conversion was probably the mechanism for this reversion, using the wild-type 23S rRNA gene sequences to replace the G2576T mutation by homologous recombination.

Acetamides↗

PubMed2004

Distribution across the USA of macrolide resistance and macrolide resistance mechanisms among Streptococcus pneumoniae isolates collected from patients with respiratory tract infections: PROTEKT US 2001-2002.

BACKGROUND: Resistance to the macrolides has increased rapidly among isolates of Streptococcus pneumoniae from community-acquired respiratory tract infections (CARTIs). METHODS: A total of 10 012 S. pneumoniae isolates were submitted from 46 US states and the territory of Puerto Rico in the PROTEKT US Year 2 (2001-2002) surveillance study. Antimicrobial susceptibilities were determined according to NCCLS guidelines and genes encoding common macrolide resistance mechanisms were sought by PCR. RESULTS: Overall, 27.9% (n=2793) of S. pneumoniae isolates were macrolide (erythromycin) resistant; the highest prevalence was recorded in Louisiana (48.2%). Of the 2738 genotyped macrolide-resistant S. pneumoniae, 68.7% possessed mef(A) (state range: Delaware 40.0%-Georgia 84.8%), 16.8% of isolates harboured erm(B) (Georgia 6.1%-Idaho and Rhode Island both 36.4%) and 12.2% possessed erm(B) + mef(A) (Arkansas and Rhode Island 0%-South Dakota 32.9%). Five isolates possessed an erm(A) subclass erm(TR) gene (from California, Illinois, Missouri, Pennsylvania and Virginia), while the mechanisms for 56 isolates were not definable by the methods used in this study. Susceptibility to telithromycin was high, irrespective of macrolide resistance mechanism, with > or =96.4% of the macrolide-resistant isolates susceptible. CONCLUSIONS: The prevalence of macrolide resistance and the resistance mechanisms among S. pneumoniae isolates are highly variable among the US states. Telithromycin may represent an effective treatment option for CARTIs caused by macrolide-resistant pneumococci.

Anti-Bacterial Agents↗

PubMed2003

Emergence of fluoroquinolone resistance among Bacteroides species.

BACKGROUND: Several newer generation fluoroquinolones have demonstrated good in vitro activity against Bacteroides species; particularly when first introduced. However, resistance of Bacteroides to quinolones appears to be increasing. MATERIALS AND METHODS: From 1994 to 2001, consecutive non-duplicated Bacteroides isolates from clinical specimens in 12 US hospitals were sent to the Tufts anaerobe laboratory for identification and susceptibility testing. NCCLS recommended methodology for testing was employed. Breakpoints of 8 mg/l for trovafloxacin and 4 mg/l for moxifloxacin were used to examine susceptibility trends. RESULTS: In total, 4434 isolates were analysed. The geometric mean MIC increased significantly for clinafloxacin, trovafloxacin and moxifloxacin. Resistance to trovafloxacin (breakpoint of 8 mg/l) and moxifloxacin (breakpoint of 4 mg/l) increased from 8% to 25% and from 30% to 43%, respectively. Increased resistance was observed for all Bacteroides species, for all sites of isolation, and in 11 of 12 participating hospitals. Bacteroides vulgatus and isolates from decubitus ulcers were associated with increased resistance. During 2001, trovafloxacin and moxifloxacin resistance among blood isolates was 27% and 52%, respectively. The association between increased resistance and year of isolation remained significant after adjustment for hospital, species and site of isolation. CONCLUSIONS: Fluoroquinolone resistance among Bacteroides isolated in the US has markedly increased during the years 1994 to 2001. High rates of resistance among blood isolates are of particular concern.

Academic Medical Centers↗

PubMed2003

Adenovirus infection in pediatric small bowel transplantation recipients.

BACKGROUND: The purpose of this study was to determine the prevalence of adenoviral infection in pediatric small bowel transplantation (SBT) recipients, examine risk factors for progression to histologic disease, and examine the impact of adenovirus on outcome. METHODS: Beginning in July 2000, all SBT recipients had viral cultures for adenovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) obtained routinely during graft biopsies. The medical records were retrospectively reviewed for frequency and site of viral culture, types and doses of immunosuppressive drugs, episodes of rejection, histology of allograft biopsies, and other infections. Adenoviral isolates were typed by polymerase chain reaction and type-specific neutralization assays. RESULTS: All 14 SBT recipients who met enrollment criteria had evidence of adenoviral infection (intestinal graft, 13; liver graft, 1). Eight of 14 developed histologic disease with identifiable adenoviral intranuclear inclusions. In contrast, CMV enteritis was identified in only one patient, who subsequently also developed adenoviral disease. No other viruses were detected. Adenoviral cultures were first positive within 30 days of transplant in nine. Patients with histologic disease were more likely than those without to have received intensive corticosteroid therapy (P<0.007), had virus isolated from more than one site (P=0.03), and had persistent positive cultures (P<0.01). CONCLUSIONS: Adenovirus was commonly isolated from children undergoing intestinal transplantation. Progression to disease may be associated with more intensive immunosuppressive therapy and inability to clear virus.

Adenoviridae Infections↗

PubMed2003

In vitro activity of gatifloxacin alone and in combination with cefepime, meropenem, piperacillin and gentamicin against multidrug-resistant organisms.

OBJECTIVES: To study the in vitro interaction of gatifloxacin in combination with gentamicin and with the beta-lactams cefepime, meropenem and piperacillin against clinical isolates of Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae, vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). METHODS: The activity of each drug alone was determined by an agar dilution method. Chequerboard synergy testing was then performed against all the isolates. Time-kill assays were done on selected isolates to assess correlation with the chequerboard results. RESULTS: Synergy was demonstrated with the following combinations at achievable serum concentrations: gatifloxacin/piperacillin for 80% and gatifloxacin/cefepime for 60% of S. maltophilia; gatifloxacin/gentamicin for 60%, and gatifloxacin/cefepime for 50% of ESBL-producing K. pneumoniae, and in all drug combinations for 50-70% of P. aeruginosa. Indifference was noted for the majority of B. cepacia and VRE isolates. Antagonism at therapeutic serum levels was observed with gatifloxacin/piperacillin against a single isolate of B. cepacia. No distinct trend in drug interaction was seen with the different drug combinations against MRSA. Time-kill analyses against selected isolates confirmed the synergic activity of the following drug combinations seen in the chequerboard assays: gatifloxacin/cefepime and gatifloxacin/piperacillin against P. aeruginosa, gatifloxacin/gentamicin against B. cepacia, and gatifloxacin/gentamicin and gatifloxacin/meropenem against ESBL-producing K. pneumoniae. CONCLUSIONS: Gatifloxacin was synergic with the beta-lactams piperacillin, cefepime and meropenem, and with gentamicin against some drug-resistant pathogens. Some of the time-kill analyses against P. aeruginosa, B. cepacia and ESBL-producing K. pneumoniae were in accordance with chequerboard results. Time-kill analyses against S. maltophilia did not confirm the synergy seen in chequerboard testing.

Anti-Bacterial Agents↗