Archive for March, 2006

Original Investigation – Management of Acute Pharyngitis in Adults Reliability of Rapid Streptococcal Tests and Clinical Findings

Source: Arch of Inter Med March 27, 2006 Vol.166 N.6 p.640-644

Jean-Paul Humair, MD, MPH; Sylvie Antonini Revaz, MD; Patrick Bovier, MD, MPH; Hans Stalder, MD Background

How to use clinical score, the rapid streptococcal antigen test (RSAT), and culture results is uncertain for efficient management of acute pharyngitis in adults.

Methods This prospective cohort study included 372 adult patients with pharyngitis treated at a Swiss university-based primary care clinic. In eligible patients with 2 to 4 clinical symptoms and signs (temperature 38°C, tonsillar exudate, tender cervical adenopathy, and no cough or rhinitis), we performed an RSAT and obtained a throat culture. We measured sensitivity and specificity of RSAT with culture as a gold standard and compared appropriate antibiotic use with cost per patient appropriately treated for the following 5 strategies: symptomatic treatment, systematic RSAT, selective RSAT, empirical antibiotic treatment, and systematic culture.

Results RSAT had high sensitivity (91%) and specificity (95%) for the diagnosis of streptococcal pharyngitis. Systematic throat culture resulted in the highest antibiotic use, in 38% of patients with streptococcal pharyngitis. Systematic RSAT led to nearly optimal treatment (94%) and antibiotic prescription (37%), with minimal antibiotic overuse (3%) and underuse (3%). Empirical antibiotic treatment in patients with 3 or 4 clinical symptoms or signs resulted in a lower rate of appropriate therapy (59%) but higher rates of antibiotic use (60%), overuse (32%), and underuse (9%). Systematic RSAT was more cost-effective than strategies based on empirical treatment or culture: $15.00, $26.00, and $32.00, respectively, per patient appropriately treated.

Conclusions The RSAT we used is a valid test for diagnosis of pharyngitis in adults. A clinical approach combining this RSAT and clinical findings efficiently reduces inappropriate antibiotic prescription in adult patients with acute pharyngitis. Empirical therapy in patients with 3 or 4 clinical symptoms or signs results in antibiotic overuse.

Author Affiliations: Medical Outpatient Clinic, Department of Community Medicine, University Hospital of Geneva, Geneva, Switzerland.

March 28, 2006 at 6:26 pm Leave a comment

Original Investigation – Current Antibiotic Therapy for Isolated Urinary Tract Infections in Women

Source: Arch of Intern Med March 27, 2006 Vol.166 N.6 p.635-639

Alexander J. Kallen, MD; H. Gilbert Welch, MD, MPH; Brenda E. Sirovich, MD, MS

Background  Sulfa antibiotics, such as a combination product of trimethoprim and sulfamethoxazole, have traditionally been the drugs of choice for urinary tract infections (UTIs) and remained the most common treatment as recently as a decade ago. However, increasing sulfa resistance among Escherichia coli may have led to changes in prescribing practices.

Methods  We used the 2000-2002 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey to obtain nationally representative data on antibiotics prescribed for women with isolated outpatient UTIs following visits to physicians' offices, hospital clinics, and emergency departments (n = 2638). Logistic regression was used to determine predictors of quinolone use.

Results  Quinolones were more commonly prescribed than sulfa antibiotics in each year evaluated. In the most recent year of data, quinolones were prescribed in 48% and sulfas in 33% of UTI visits (P<.04). Quinolones were significantly more likely to be prescribed to older patients and in visits occurring in the Northeast; however, no difference in quinolone prescribing was seen when evaluating insurance status, setting, race, ethnicity, health care provider type, and year. Approximately one third of the quinolones used were broader-spectrum agents.

Conclusions  Quinolones have surpassed sulfas as the most common class of antibiotic prescribed for isolated outpatient UTI in women. Few significant predictors of quinolone use exist, suggesting that the increase is not confined to a certain subset of patients. This pervasive growth in quinolone use raises concerns about increases in resistance to this important class of antibiotics.

Author Affiliations: VA Outcomes Group, VA Medical Center, White River Junction, Vt, and Dartmouth Medical School, Hanover, NH.

March 28, 2006 at 6:22 pm Leave a comment

State of the Art – Current Approaches to Diagnosis and Treatment of Invasive Aspergillosis

Source: Am. J. Respir. Crit. Care Med. Apr 2006 vol.173 n.7 p.707-717

Brahm H. Segal and Thomas J. Walsh

Department of Medicine, SUNY at Buffalo, Division of Infectious Diseases, Roswell Park Cancer Institute, Buffalo, New York; and Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Correspondence and requests for reprints should be addressed to Brahm H. Segal, M.D., Assistant Professor of Medicine, Department of Medicine, SUNY at Buffalo, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263. E-mail:

Filamentous fungi (moulds) are ubiquitous soil inhabitants whose conidia are inhaled into the respiratory tract, where they may cause life-threatening infections. Among these infections is invasive aspergillosis, which is a major cause of morbidity and mortality in the severely immunocompromised.

Risk factors for invasive aspergillosis include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. Invasive aspergillosis most commonly involves the sinopulmonary tract reflecting inhalation as the principal portal of entry. Chest computed tomography scans and new non-culture–based assays such as antigen detection and polymerase chain reaction may facilitate the early diagnosis of invasive aspergillosis, but have limitations.

Reflecting an important unmet need, there has been a significant expansion in the antifungal armamentarium. The second-generation triazole, voriconazole, was superior to conventional amphotericin B as primary therapy for invasive aspergillosis, and is the new standard of care for this infection.

There is significant interest in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B formulation as therapy for invasive aspergillosis.

In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials.


March 23, 2006 at 5:07 pm Leave a comment

MAJOR ARTICLE – CD4 Cell Response to Antiretroviral Therapy in Children with Vertically Acquired HIV Infection: Is It Associated with Age at Initiation?

Source: The Journal of Infectious Diseases 1 Apr 2006 vol.193 n.7   p.954-962

European Collaborative Study

Background. Considerable uncertainty remains as to whether early initiation of antiretroviral therapy (ART) in children with vertically acquired human immunodeficiency virus (HIV) infection increases the benefit in terms of immunological response.

Methods. The association between immunological outcome and early initiation of and/or more-potent ART was investigated, using age-standardized z scores for CD4 cell counts (hereafter, “CD4 z scores”), in 131 HIV-infected children enrolled in the European Collaborative Study, a birth cohort study.

Results. Median age at initiation of the most-potent ART was 4 years (range, 0.1–15.5 years). Initiation of treatment after 5 months of age resulted in nonsignificantly lower CD4 z scores 6 months after initiation. Time to a 20% increase in CD4 z score was associated with age at initiation of the most-potent ART (adjusted hazard ratios [AHRs], 0.37 [P 5 years of age, respectively, compared with Conclusions. We confirm the effectiveness of HAART with respect to the recovery of CD4 cell count and suggest a benefit of initiating ART before the age of 5 months. Age at initiation of the most-potent ART was not associated with the likelihood of sustaining the recovery of CD4 cell count.

Potential conflicts of interest: none reported.
Financial support: European Commission (concerted action grant QLK2-CT-2000-00002); United Kingdom Medical Research Council Sexual Health and HIV Strategy Committee (support to the European Collaborative Study Coordinating Centre). The views expressed here are those of the authors.
a Prepared by Marie-Louise Newell (Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, United Kingdom), Deven Patel (Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London), Tessa Goetghebuer (Hôpital St Pierre, Brussels, Belgium), and Claire Thorne (Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London). European Collaborative Study collaborators are listed at the end of the text.

March 22, 2006 at 11:39 am Leave a comment

MAJOR ARTICLE – The Spectrum of Genital Herpes Simplex Virus Infection in Men Attending a Sexually Transmitted Disease Clinic

Source: The Journal of Infectious Diseases 1 Apr 2006 vol.193 n.7 p.905-911

James M. Sizemore, Jr.,1,a Fred Lakeman,2 Richard Whitley,2 Annalee Hughes,1 and Edward W. Hook III1,3

1Division of Infectious Diseases, Department of Medicine, and 2Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, and 3Jefferson County Department of Health, Birmingham, Alabama

Background. The spectrum of genital herpes (GH) has been understudied in men, especially African American men.

Methods. Consecutive men attending a sexually transmitted diseases clinic were enrolled in a study of GH epidemiology. Consenting participants answered questionnaires detailing their sexual and social activities and underwent serological testing for herpes simplex virus types 1 and 2 (HSV-1 and -2) and collection of genital swabs for viral detection.

Results. Of the 516 men enrolled, 465 (90%) were African American. Antibodies to HSV-1 were present in 315 (61%) of participants, and 233 (45%) had antibodies to HSV-2. Factors associated with HSV-2 infection included older age and African American race. HSV was detected in genital swabs from 52 men; 43 (82.7%) swabs were HSV-2 positive, and 9 (17.3%) were HSV-1 positive. The overall viral shedding rate among men (n = 247) with evidence of GH (HSV-1 or HSV-2 infection) was 21.1%, and the asymptomatic shedding rate in this same group was 5.2%. The sensitivities of culture for detection of HSV-1 and HSV-2 were .22 and .58, respectively, compared with that of polymerase chain reaction.

Conclusions. Genital HSV infections are common and largely unrecognized among this segment of the population. HSV-1 infection constitutes a nontrivial proportion of GH in these men.

Presented in part: 2005 International Society of STD Research Conference, Amsterdam, The Netherlands, 10–13 July 2005 (abstract 817).
Potential conflicts of interest: E.W.H. and R.W. have received research support from—and E.W.H., R.W., and J.M.S. have received honoraria from—GlaxoSmithKline.
Financial support: University of Alabama at Birmingham Sexually Transmitted Diseases Cooperative Research Center (grant 5 U19 AI38514-07); GlaxoSmithKline.
a Present affiliation: University of Tennessee, Chattanooga.

March 22, 2006 at 11:37 am Leave a comment

Concentration of moxifloxacin in plasma and tonsillar tissue after multiple administration in adult patients

Source: Journal of Antimicrobial Chemotherapy Apr 2006 vol.57 n.4 p.789-792

Silvano Esposito1,*, Silvana Noviello1, Gioacchino D’Errico2, Gaetano Motta2, Desiderio Passali3, Claudia Aimoni4, Stefano Pilucchi4, Stefania Fallani5, Maria Iris Cassetta5, Teresita Mazzei5 and Andrea Novelli5

1 Dipartimento di Malattie Infettive, Seconda Università di Napoli, Italy; 2 Dipartimento di Otorinolaringoiatria, Seconda Università di Napoli, Italy; 3 Clinica Otorinolaringoiatrica, Università degli Studi di Siena, Italy; 4 Dipartimento di Discipline Medico Chirurgiche della Comunicazione e del Comportamento, Sez. ORL, Università degli Studi di Ferrara, Italy; 5 Istituto di Farmacologia Preclinica e Clinica, Università di Firenze, Italy

* Correspondence address. Clinica Malattie Infettive, Ospedale Gesù e Maria, Seconda Università degli Studi di Napoli, Via D. Cotugno 1, 80135 Napoli, Italy. Tel: +39-081-5666218; Fax: +39-081-5666203; E-mail:

Objectives: The antibacterial spectrum of moxifloxacin includes all the major respiratory pathogens, and its pharmacokinetics demonstrate high peak concentrations in plasma as well as at respiratory sites.

Nevertheless, tonsillar tissue concentrations have never been investigated. In this study we determined the moxifloxacin concentrations in plasma and tonsillar tissue after the administration of three doses of moxifloxacin 400 mg to adult patients with chronic or recurrent tonsillitis undergoing tonsillectomy.

Methods: This was an uncontrolled, open-label, randomized, parallel group study including 35 patients assigned randomly to five groups of 7 patients each, depending on the time between the last dose of moxifloxacin and plasma and tissue sampling. Moxifloxacin was given orally once daily for 3 days; its concentrations were measured using a validated HPLC assay and fluorescence detection. Each sample was analysed twice and the mean value obtained used for the statistical analysis. Pharmacokinetic data were analysed by presenting descriptive statistics of moxifloxacin concentrations in plasma and tonsillar tissue.

Results: Cmax occurred at 3 h in tonsillar tissue (mean 8.96 mg/L) and in plasma (mean 3.20 mg/L), the tissue/plasma concentration ratios (mean values) being constantly >2, ranging between 2.37 (after 2 h) and 2.93 (after 24 h), which indicates a prolonged maintenance of moxifloxacin concentration in tonsillar tissue compared with plasma. Variability among patients was present at 6 h, with the tonsillar tissue/plasma concentration ratio ranging between 0.8 and 3.4.

Conclusions: Moxifloxacin achieves a good penetration in tonsillar tissue, which compares favourably with that reported for other fluoroquinolones. The moxifloxacin concentrations we observed exceed the MICs for the usual respiratory tract pathogens.

March 19, 2006 at 9:47 pm Leave a comment

Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia

Source: Journal of Antimicrobial Chemotherapy Apr 2006 vol.57 n.4 p.699-704

George Sakoulas1,*, Howard S. Gold2,3, Robert A. Cohen2,3, Lata Venkataraman2, Robert C. Moellering2,3 and George M. Eliopoulos2,3

1 Westchester Medical Center and New York Medical College, Valhalla, NY, USA; 2 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3 Harvard Medical School, Boston, MA, USA

* Corresponding author. Tel: +1-914-594-4974; Fax: +1-845-361-1156; E-mail:

Objectives: To evaluate microbiological properties of methicillin-resistant Staphylococcus aureus (MRSA) during prolonged vancomycin therapy.

Methods: We evaluated vancomycin susceptibility and heteroresistance, accessory gene regulator (agr) function, autolysis, biofilm production and in vitro vancomycin killing in serial MRSA bloodstream isolates obtained over a 30 month period from a patient with a chronic endovascular infection.

Results: Despite the fact that the MRSA in this patient had the same genetic background as other clinical glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin administered for 9 months, maintaining serum concentrations >10 mg/L, did not select for GISA.

Minimal changes in vancomycin susceptibility were detected using agar dilution and population analysis methods. We noted increases in delta haemolysin production, autolysis and the bactericidal effects of vancomycin in vitro against the MRSA obtained after prolonged vancomycin suppressive therapy was discontinued.

Conclusions: Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.


March 19, 2006 at 9:44 pm Leave a comment

Identification and characterization of ceftriaxone resistance and extended-spectrum ß-lactamases in Malawian bacteraemic Enterobacteriaceae

Source: Journal of Antimicrobial Chemotherapy Apr 2006 vol.57 n.4 p.661-665

Katherine J. Gray1,2,*, Lorna K. Wilson1, Amos Phiri1, John E. Corkill2, Neil French1,3 and C. Anthony Hart2

1 Malawi-Liverpool-Wellcome Trust Laboratories, PO Box 30096, Blantyre, Malawi; 2 Department of Medical Microbiology, Royal Liverpool University Hospital, Liverpool L7 8XP, UK; 3 Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK

* Corresponding author. Tel: +265-167-6444; Fax: +265-167-5774; E-mail:

Objectives: To enumerate and characterize extended-spectrum ß-lactamases (ESBLs) amongst ceftriaxone-resistant coliforms in Blantyre, Malawi, where third-generation cephalosporin use is currently highly restricted.

Methods: Over the period April 2004–March 2005 all ceftriaxone-resistant isolates from blood cultures were examined for the presence of ESBLs. Isoelectric focusing was performed on enzyme extracts. PCR and DNA sequencing of amplicons were used to identify the underlying genetic determinants responsible for the ESBL phenotypes. Transferability of the ESBL phenotypes was tested by conjugation to a susceptible Escherichia coli J53.

Results: Enterobacteriaceae were isolated from 1191 blood cultures, of which 19 (1.6%) were ceftriaxone resistant. Ten isolates (0.7% of all isolates) demonstrated an ESBL phenotype but only eight were characterized as three isolates were from the same patient. Genotypes SHV-11 (n = 1), SHV-12 (n = 3), SHV-27 (n = 1), TEM-63 (n = 2) and CTX-M-15 (n = 1) were detected. Plasmid transfer of the ESBL resistance phenotype was successful for all the isolates.

Conclusions: In a clinical setting of minimal cephalosporin usage there is already a diversity of ESBL genotypes. Increased use of cephalosporins in this setting is likely to result in a rapid expansion of ESBLs and their prevalence will need to be carefully monitored.


March 19, 2006 at 9:42 pm Leave a comment

Molecular epidemiology and variants of the multidrug-resistant Streptococcus pneumoniae Spain14-5 international clone among Spanish clinical isolates

Source: Journal of Antimicrobial Chemotherapy Apr 2006 vol.57 n.4 p.654-660

José María Marimón1, Emilio Pérez-Trallero1,2,*, María Ercibengoa1, Alberto Gonzalez1, Asunción Fenoll3 on behalf of the Spanish Pneumococcal Infection Study Network (G03/103)

1 Servicio de Microbiología, Hospital Donostia Paseo Dr Beguiristain s/n 20014 San Sebastián, Spain; 2 Departamento de Medicina Preventiva y Salud Pública, Universidad del País Vasco, Paseo Dr Beguiristain s/n 20014 San Sebastián, Spain; 3 Centro Nacional de Microbiología, Majadahonda, Madrid, Spain

* Corresponding author. Tel: +34-94-300-7046; Fax: +34-94-300-7063; E-mail:

Objective: To analyse the molecular structure of several antimicrobial resistance determinants in isolates of the Spain14-5 clone to better understand its emergence and spread.

Methods: The distinct genes and mechanism of resistance to penicillin, erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim were studied in an apparently homogeneous group of 117 isolates of the multidrug-resistant Spain14-5 major clone isolated in Spain between 1981 and 2004.

Results: Several genotyping techniques such as PFGE, BOX-PCR and multilocus sequence typing (MLST) revealed a high degree of homogeneity among these isolates over time. Nevertheless, distinct variants of the clone could be established according to the restriction fragment length polymorphism (RFLP) patterns of the penicillin-binding protein (pbp) genes and the sequences of the dihydrofolate reductase (dhfr) gene. In addition, an association between the pbp2b RFLP patterns, the ddl alleles identified by MLST and the dhfr alleles was found. The emergence of variants of the Spain14-5 clone, which had lost macrolide and tetracycline resistance, while harbouring the ins and xis genes of the Tn916–Tn1545 family of conjugative transposons, was documented. Two different tet(M) alleles were detected in isolates of the clone, one of them with a mosaic structure.

Conclusions: The finding of different patterns or alleles of the genes responsible for antibiotic resistance among isolates of the Spain14-5 clone from different Spanish cities indicates different evolutionary events within isolates of a unique Streptococcus pneumoniae clone.


March 19, 2006 at 9:39 pm Leave a comment

The role of aminoglycosides in combination with a ß-lactam for the treatment of bacterial endocarditis: a meta-analysis of comparative trials

Source: Journal of Antimicrobial Chemotherapy Apr 2006 vol.57 n.4 p.639-647

Systematic review

Matthew E. Falagas1,2,*, Dimitrios K. Matthaiou1 and Ioannis A. Bliziotis1

1 Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; 2 Department of Medicine, Tufts University School of Medicine, Boston, MA, USA

* Correspondence author. Tel: +30-694-611-0000; Fax: +30-210-683-9605; E-mail:

Background: The addition of an aminoglycoside to a ß-lactam for the treatment of patients with infective endocarditis has been supported by data from laboratory and animal studies.

Purpose: We sought to review the evidence from the available comparative clinical trials regarding the role of aminoglycosides in combination with a ß-lactam for the treatment of bacterial endocarditis caused by Gram-positive cocci.

Data sources: The studies for our meta-analysis were retrieved from searches of the PubMed and Cochrane Central Register of Controlled Trials databases, as well as from the references cited in relevant articles. No limits were set regarding the language and date of publication of the studies.

Study selection: Included studies were prospective studies that provided comparative data regarding the effectiveness of the treatment and/or mortality in patients receiving monotherapy with a ß-lactam or ß-lactam/aminoglycoside combination therapy.

Data extraction: Two independent reviewers performed the literature search, study selection and extraction of data from relevant studies.

Data synthesis: No clinical trial comparing ß-lactam monotherapy with ß-lactam/aminoglycoside combination therapy for the treatment of enterococcal endocarditis was found. We performed a meta-analysis of five available comparative trials [four randomized controlled trials (RCTs) and one comparative prospective trial], which included 261 patients with bacterial endocarditis in native valves due to Staphylococcus aureus (four studies) or streptococci of the viridans group (one study). There was no statistically significant difference between ß-lactam monotherapy and ß-lactam/aminoglycoside combination therapy regarding mortality [odds ratio (OR) = 0.59, 95% confidence interval (95% CI) = 0.21–1.66], treatment success (OR = 1.25, 95% CI = 0.49–3.05), treatment success without surgery (OR = 1.66, 95% CI = 0.64–4.30) or relapse of endocarditis (OR = 0.79, 95% CI = 0.15–4.29).

Nephrotoxicity was less common in the ß-lactam monotherapy arm than in the ß-lactam/aminoglycoside combination therapy arm (OR = 0.38, 95% CI = 0.16–0.88, P = 0.024). No difference between the two treatment arms was found in subanalyses of the four studies that included only patients with staphylococcal infections in terms of mortality (OR = 0.69, 95% CI = 0.26–1.86, fixed effects model), treatment success (OR = 1.27, 95% CI = 0.47–3.43, fixed effects model) or relapse (OR = 0.76, 95% CI = 0.12–4.92, fixed effects model).

Limitations: The relatively small number of available comparative trials was the major limitation of this meta-analysis.

Conclusions: The limited evidence from the available prospective comparative studies does not offer support for the addition of an aminoglycoside to ß-lactam treatment of patients with endocarditis caused by Gram-positive cocci. A large multicentre RCT is necessary to reach a definitive conclusion on this issue.

March 19, 2006 at 9:36 pm Leave a comment

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