Archive for January, 2006

Clinical Evaluation of Macrolide-Resistant Mycoplasma pneumoniae

Source: Antimicrobial Agents and Chemotherapy Feb 2006 vol.50 N.2 p. 709-712


Satowa Suzuki,1 Tsutomu Yamazaki,2 Mitsuo Narita,3 Norio Okazaki,4 Isao Suzuki,5 Tomoaki Andoh,5 Mayumi Matsuoka,1 Tsuyoshi Kenri,1 Yoshichika Arakawa,1 and Tsuguo Sasaki1*

Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo,1 Department of Pediatrics, Saitama Medical School, Saitama,2 Sapporo Tetsudo Hospital, Hokkaido,3 Kanagawa Prefectural Institute of Public Health, Kanagawa,4 Department of Pediatrics, Chigasaki Municipal Hospital, Kanagawa, Japan5

Macrolide-resistant Mycoplasma pneumoniae (MR M. pneumoniae) has been isolated from clinical specimens in Japan since 2000. A comparative study was carried out to determine whether or not macrolides are effective in treating patients infected with MR M. pneumoniae. The clinical courses of 11 patients with MR M. pneumoniae infection (MR patients) treated with macrolides were compared with those of 26 patients with macrolide-susceptible M. pneumoniae infection (MS patients). The total febrile days and the number of febrile days during macrolide administration were longer in the MR patients than in the MS patients (median of 8 days versus median of 5 days [P = 0.019] and 3 days versus 1 day [P = 0.002], respectively). In addition, the MR patients were more likely than the MS patients to have had a change of the initially prescribed macrolide to another antimicrobial agent (63.6% versus 3.8%; odds ratio, 43.8; P * Corresponding author. Mailing address: Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan. Phone: (81) 425610771. Fax: (81) 425653315. E-mail:

January 26, 2006 at 11:11 am Leave a comment

Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection

Source: Antimicrobial Agents and Chemotherapy Feb 2006 vol.50 N.2 p. 658-666

A. J. Ullmann,1* O. A. Cornely,2 A. Burchardt,1 R. Hachem,3 D. P. Kontoyiannis,3 K. Töpelt,2 R. Courtney,4, D. Wexler,4 G. Krishna,4 M. Martinho,4 G. Corcoran,4, and I. Raad3

Third Medical Department, Johannes Gutenberg-University, Mainz, Germany,1 University of Köln, Köln, Germany,2 The University of Texas MD Anderson Cancer Center, Houston, Texas,3 Schering-Plough Research Institute, Kenilworth, New Jersey4

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.).

Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P * Corresponding author. Mailing address: III Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz, Langenbeckstraße 1, 55101 Mainz, Germany. Phone: 49 6131 17 6564. Fax: 49 6131 17 476564. E-mail:

Present address: Pfizer, San Diego, CA.
Present address: Stiefel, Miami, FL.

January 26, 2006 at 11:09 am Leave a comment

Bloodstream Infections Caused by Extended-Spectrum-ß-Lactamase-Producing Klebsiella pneumoniae: Risk Factors, Molecular Epidemiology, and Clinical Outcome

Source: Antimicrobial Agents and Chemotherapy Feb 2006 vol.50 N.2 p. 498-504

Mario Tumbarello,1* Teresa Spanu,2 Maurizio Sanguinetti,2 Rita Citton,1 Eva Montuori,1 Fiammetta Leone,2 Giovanni Fadda,2 and Roberto Cauda1

Departments of Infectious Diseases,1 Microbiology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy2

Bloodstream infections caused by extended-spectrum-ß-lactamase (ESBL)-producing Klebsiella pneumoniae isolates are a major concern for clinicians, since they markedly increase the rates of treatment failure and death. One hundred forty-seven patients with K. pneumoniae bloodstream infections were identified over a 5-year period (January 1999 to December 2003). The production of ESBLs in bloodstream isolates was evaluated by molecular methods. A retrospective case-case-control study was conducted to identify risk factors for the isolation of ESBL-producing K. pneumoniae or non-ESBL-producing K. pneumoniae isolates in blood cultures. Forty-eight cases infected with ESBL-producing K. pneumoniae isolates and 99 cases infected with non-ESBL-producing K. pneumoniae isolates were compared to controls.

Risk factors for isolation of ESBL-producing K. pneumoniae isolates were exposure to antibiotic therapy (odds ratio [OR], 11.81; 95% confidence interval [CI], 2.72 to 51.08), age (OR, 1.14; 95% CI, 1.08 to 1.21), and length of hospitalization (OR, 1.10; 95% CI, 1.04 to 1.16). Independent determinants for isolation of non-ESBL-producing K. pneumoniae were previous urinary tract infection (OR, 8.50; 95% CI, 3.69 to 19.54) and length of hospitalization (OR, 1.07; 95% CI, 1.04 to 1.10). When the initial response was assessed at 72 h after antimicrobial therapy, the treatment failure rate for the ESBL-producing K. pneumoniae-infected group was almost twice as high as that of the non-ESBL-producing K. pneumoniae-infected group (31% versus 17%; OR, 2.19; 95% CI, 0.98 to 4.89). The 21-day mortality rate for all patients was 37% (54 of 147); it was 52% (25 of 48) for patients with ESBL-producing K. pneumoniae bloodstream infections and 29% (29 of 99) for patients with non-ESBL-producing K. pneumoniae bloodstream infections (OR, 2.62; 95% CI, 1.28 to 5.35). In summary, this investigation identifies epidemiological characteristics that distinguish ESBL-producing K. pneumoniae infections from non-ESBL-producing K. pneumoniae ESBL bloodstream infections.

* Corresponding author. Mailing address: Istituto Malattie Infettive, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy. Phone: 39-06-30155373. Fax: 39-06-3054519. E-mail:

January 26, 2006 at 11:06 am Leave a comment

Antimicrobial practice – Adjustment of antibiotic treatment according to the results of blood cultures leads to decreased antibiotic use and costs

Source: Journal of Antimicrobial Chemotherapy 2006 vol.57 N.2 p.326-330

Dag Berild1,*, Atefeh Mohseni1, Lien My Diep2, Mogens Jensenius1 and Signe Holta Ringertz3

1 Department of Internal Medicine, Aker University Hospital, N-0514 Oslo, Norway; 2 Research Centre, Aker University Hospital, N-0514 Oslo, Norway; 3 Department of Microbiology, Aker University Hospital, N-0514 Oslo, Norway

* Corresponding author. Tel: +47-22894808; Fax: +47-22894008; E-mail:

Introduction: To avoid the use of unnecessary broad-spectrum antibiotics, empirical therapy of bacteraemia should be adjusted according to the results of blood cultures.

Objectives: To investigate whether the results of blood cultures led to changes in antibiotic use and costs in a tertiary-care university hospital in Norway.

Methods: Medical records from all patients with positive blood cultures in 2001 were analysed retrospectively. Factors predisposing to infections, results of blood cultures, antibiotic use and outcome were recorded. The influence of blood culture results on antibiotic treatment and costs were analysed.

Results: The antibiotic use in 226 episodes of bacteraemia in 214 patients was analysed. According to the guidelines empirical antibiotic treatment should be adjusted in 166 episodes. Antibiotic use was adjusted in 146 (88%) of these 166 episodes, which led to a narrowing of therapy in 118 (80%) episodes. Compared with empirical therapy there was a 22% reduction in the number of antibiotics. Adjustment of therapy was more often performed in Gram-negative bacteraemia and polymicrobial cultures than in Gram-positive bacteraemia. In bacteraemia caused by ampicillin-resistant Escherichia coli, ampicillin was mostly replaced by ciprofloxacin. The cost for 7 days adjusted therapy in 146 episodes was 19 800 (23%) less than for 7 days of empirical therapy.

Conclusions: Adjustment of antibiotic therapy according to the results of blood cultures led to a reduction in the number of antibiotics and a narrowing of antibiotic therapy. The costs for antibiotics decreased.


January 24, 2006 at 5:18 pm Leave a comment

Oxazolidinone susceptibility patterns in 2004: report from the Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program assessing isolates from 16 nations

Source: Journal of Antimicrobial Chemotherapy 2006 vol.57 N.2 p.279-287

Ronald N. Jones1,2,*, James E. Ross1, Thomas R. Fritsche1 and Helio S. Sader1

1 JMI Laboratories, Inc., 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA; 2 Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA

* Corresponding author. Tel: +1-319-665-3370; Fax: +1-319-665-3371; E-mail:

Objectives: To investigate the activity of linezolid (an oxazolidinone), a potent choice for community- and hospital-acquired infections, via a worldwide surveillance network called the Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program.

Methods: A total of 4098 Gram-positive strains were collected from 42 laboratories located in North America (five sites in Canada), South America (10 sites), Europe (16 sites) and the Far East (11 sites). Each country or site submitted 200 isolates (Canada submitted 200 isolates for each of five sites; total 1000) for confirmation of organism identification and reference MIC processing. Nearly 25 comparator agents were tested along with quality control strains, and interpretative criteria from the CLSI, formerly the NCCLS, M100-S15 were applied. No linezolid resistance was detected in strains from 16 monitored countries in 2004.

Results: Linezolid remained highly active against Streptococcus pneumoniae, viridans group and ß-haemolytic streptococci (MIC90, 1 mg/L). Against Staphylococcus aureus, linezolid showed 99.5% of results at 0.5–2 mg/L with only one isolate at 4 mg/L. Oxacillin-resistant S. aureus rates varied between nations and ranged from 1.4% in Sweden to 29.5% in the UK to 65.2% in Mexico. Linezolid MIC values were generally one log2 dilution step lower for coagulase-negative staphylococci (CoNS) when compared with S. aureus. No CoNS strains produced a linezolid result at 4 mg/L. Compared with ZAAPS 2002 and 2003 results for enterococci where seven resistant strains were identified, the 2004 data revealed no resistance and 98.1% of linezolid MIC results were at 1 or 2 mg/L. Vancomycin-resistant enterococci (5.3% overall) varied markedly by country including a high of 47.2% in Korea.

Conclusions: Linezolid continues to be effective in vitro against Gram-positive pathogens from five continents and no oxazolidinone-resistant strains were identified among the 4098 systemically collected strains (2004) or among 20 158 non-United States isolates for the entire ZAAPS Program (2002–04).

January 24, 2006 at 5:15 pm Leave a comment

Systematic review – Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials

Source: Journal of Antimicrobial Chemotherapy 2006 vol.57 N.2 p.176-189

Mical Paul1,2,*, Dafna Yahav1, Abigail Fraser1 and Leonard Leibovici1,2

1 Department of Medicine E, Rabin Medical Center, Beilinson Campus, 49100 Petah-Tiqva, Israel; 2 Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

* Corresponding author. Tel: +972-3-9376501; Fax: +972-3-9376512; E-mail:

Objectives: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several ß-lactams are accepted for monotherapy. We asked whether patients’ outcomes are influenced by the chosen ß-lactam.

Methods: Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal ß-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same ß-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality.

Results: Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other ß-lactams (RR 1.44, 95% CI 1.06–1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24–3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality.

Conclusions: The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis.

Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.

January 24, 2006 at 5:13 pm Leave a comment

Meeting report – Resistance is futile—a conference to promote the rational use of antimicrobials in acute hospitals

Source: Journal of Antimicrobial Chemotherapy 2006 vol.57 N.2 p.171-175

Colin W. E. Drummond*

Editorial Office, Journal of Antimicrobial Chemotherapy, 11 The Wharf, 16 Bridge Street, Birmingham, B1 2JS, UK

* Tel: +44-121-633-0415; Fax: +44-121-643-9497; E-mail:

This article reports on the proceedings of a meeting held in London in July 2005 organized by the Specialist Advisory Committee on Antimicrobial Resistance in conjunction with the UK National Prescribing Centre and UK Department of Health. The focus of the meeting was the developing role of the antibiotic pharmacist. The main presentations tackled four aspects of hospital antimicrobial prescribing: the development, maintenance and presentation of guidelines; the role of prescriber education; the importance of team working in multidisciplinary prescribing networks; and preliminary findings on hospital antibiotic consumption in England. The speakers highlighted the progress that has been made and gave examples of good practice, in addition they drew attention to deficiencies and hence the challenges that lie ahead. These include the need for accurate hospital antibiotic usage data in the UK and more integration of clinical outcome data in studies on the control of antimicrobial consumption through the implementation of prescribing guidelines.

January 24, 2006 at 5:10 pm Leave a comment

Leading article – Reducing HIV-1 transmission through prevention strategies targeting HIV-1-seropositive individuals

Source: Journal of Antimicrobial Chemotherapy 2006 vol.57 N.2 p.163-166

R. Scott McClelland* and Jared M. Baeten

Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA

* Corresponding author. Tel: +1-206-543-4278; Fax: +1-206-543-4818; E-mail:

Prevention efforts for HIV-1 have traditionally focused on those at risk for acquiring the virus. Recently, there has been growing interest in directing prevention efforts towards HIV-1-seropositive individuals, who are seeking care in increasing numbers as a result of improving access to antiretroviral therapy in resource-limited countries. Biomedical interventions aimed at reducing the spread of HIV-1 by targeting those at risk for transmitting the virus will be guided in part by an understanding of the bidirectional interactions between HIV-1 and other sexually transmitted diseases (STDs). Among those who are infected with HIV-1, STDs are common, and immunosuppression may further increase STD risk. In turn, the presence of an STD increases the concentration of HIV-1 in genital mucosal secretions. Both antiretroviral therapy and treatment of STDs can lower genital HIV-1 concentrations, suggesting that these approaches may reduce infectivity. Thus, the growing availability of HIV-1 and STD treatment in the countries most affected by the HIV-1 epidemic provides a unique and important opportunity to develop prevention strategies that target HIV-1/STD interactions at multiple levels. Further work is urgently needed to develop, test and implement comprehensive strategies for prevention in positives.

January 24, 2006 at 5:06 pm Leave a comment

Candida Colonization of the Respiratory Tract and Subsequent Pseudomonas Ventilator-Associated Pneumonia*

Source: Chest. Jan 2006 vol.129 N.1 p.110-117

Elie Azoulay, MD, PhD; Jean-François Timsit, MD, PhD; Muriel Tafflet; Arnaud de Lassence, MD; Michael Darmon, MD; Jean-Ralph Zahar, MD; Christophe Adrie, MD, PhD; Maité Garrouste-Orgeas, MD; Yves Cohen, MD; Bruno Mourvillier, MD; Benoît Schlemmer, MD; the Outcomerea Study Group

* From the Medical ICU (Drs. Azoulay, Darmon, and Schlemmer), Saint Louis Teaching Hospital, Paris; Medical ICU (Dr. Timsit), Hospital Michallon, Grenoble; Department of Biostatistics (Ms. Tafflet), Outcomerea; Louis Mourier Teaching Hospital (Dr. de Lassence), Colombes; Microbiology Department (Dr. Zahar), Necker Teaching Hospital, Necker; Medical-Surgical ICU (Dr. Adrie), Delafontaine Hospital, Saint Denis; Medical-Surgical ICU (Dr. Garrouste-Orgeas), Saint Joseph Teaching Hospital, Paris; Medical-surgical ICU (Dr. Cohen), Avicenne Teaching Hospital, Bobigny; and Medical ICU (Dr. Mourvillier), Bichat Hospital, Paris, France.  The members of the Outcomerea study group are listed in the Appendix.

Correspondence to: Elie Azoulay, MD, PhD, Medical ICU, Saint Louis Teaching Hospital, 1 Ave Claude Vellefaux, 75010 Paris, France; e-mail:


Background: Recovery of Candida from the respiratory tract of a critically ill patient receiving mechanical ventilation (MV) usually indicates colonization rather than infection of the respiratory tract. However, interactions between Candida and bacteria, particularly Pseudomonas, have been reported. Thus, Candida colonization of the respiratory tract may predispose to bacterial ventilator-associated pneumonia (VAP).

Methods: In a multicenter study of immunocompetent critically ill patients receiving MV for > 2 days, we compared the incidence of pneumonia in patients with and without (exposed/unexposed) respiratory-tract Candida colonization, matched on study center, admission year, and MV duration.

Results: Over the 4-year study period, of the 803 patients meeting study inclusion criteria in the six study centers, 214 patients (26.6%) had respiratory tract Candida colonization. Candida albicans was the most common species (68.7%), followed by Candida glabrata (20.1%) and Candida tropicalis (13.1%). Extrapulmonary Candida colonization was more common in exposed patients (39.7% vs 8.3%, p = 0.01). Exposed patients had longer ICU and hospital stays but similar mortality to unexposed patients. The matched exposed/unexposed nested cohort study identified bronchial Candida colonization as an independent risk factor for pneumonia (24.1% vs 17.6%; adjusted odds ratio [OR], 1.58; 95% confidence interval [CI], 0.94 to 2.68; p = 0.0860); the risk increase was greatest for Pseudomonas pneumonia (9% vs 4.8%; adjusted OR, 2.22; 95% CI, 1.00 to 4.92; p = 0.049).

Conclusions: Candida colonization of the respiratory tract is common in patients receiving MV for > 2 days and is associated with prolonged ICU and hospital stays, and with an increased risk of Pseudomonas VAP.


January 21, 2006 at 11:29 am Leave a comment

Fulminant Community-Acquired Acinetobacter baumannii Pneumonia as a Distinct Clinical Syndrome*

Source: Chest. Jan 2006 vol.129 N.1 p.102-109

Wah-Shing Leung, MRCP; Chung-Ming Chu, FCCP; Kay-Yang Tsang, MRCP; Fu-Hang Lo, MRCP; King-Fan Lo, MRCP and Pak-Leung Ho, MRCPath

* From the Department of Medicine and Geriatrics (Drs. Leung, Chu, Tsang, F.-H. Lo, and K.-F. Lo), United Christian Hospital, Hong Kong SAR, Peoples Republic of China; and the Department of Microbiology (Dr. Ho), Division of Infectious Disease, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, Peoples Republic of China.

Correspondence to: Pak-Leung Ho, Division of Infectious Disease, Department of Microbiology and Centre of Infection, Queen Mary Hospital, University of Hong Kong, Pokfulam Rd, Pokfulam, Hong Kong SAR, Peoples Republic of China; e-mail:


Study objectives: Acinetobacter baumannii (AB) is an important cause of hospital-acquired pneumonia (HAP), and an uncommon but important cause of community-acquired pneumonia (CAP) with high mortality. To better characterize CAP-AB, we compared its clinical features and outcomes with a control group of HAP-AB patients.

Methods: This is a retrospective case-control study comparing CAP-AB and HAP-AB patients, which was performed at United Christian Hospital between July 2000 and December 2003.

Results: There were 19 cases of CAP-AB and 74 cases of HAP-AB. When compared with the HAP-AB group, the CAP-AB group had more ever-smokers (84.3% vs 55.4%, respectively; p = 0.031), more COPD patients (63.2% vs 29.7%, respectively; p = 0.014), and fewer median days of hospitalization (HAP-AB group, median, 0 days; CAP-AB group, 0 days [range, 0 to 30 days]; p = 0.049) in the previous year. The CAP-AB group had more patients with positive blood culture findings (31.6% vs 0%, respectively; p Conclusions: CAP-AB appears to be a unique clinical entity with a high incidence of bacteremia, ARDS, DIC, and death, when compared to HAP-AB. Further studies are needed to investigate the mechanism of the fulminant nature of CAP-AB.

January 21, 2006 at 11:27 am Leave a comment

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