Archive for December, 2008

Infections Caused by Viridans Streptococci in Patients with Neutropenia

Clinical Infectious Diseases  1 Jun 2002  V.34  N.11  p.1524-1529


Allan R. Tunkel1 and Kent A. Sepkowitz2

1Division of Infectious Diseases, Department of Medicine, MCP Hahnemann University, Philadelphia, Pennsylvania; and 2Clinical Infectious Disease Section, Memorial Sloan-Kettering Cancer Center, New York, New York

The frequency of isolation of viridans streptococci from the blood of neutropenic patients with cancer has significantly increased over the course of the last 10–15 years. Risk factors in this patient population include severe neutropenia, oral mucositis, administration of high-dose cytosine arabinoside, and antimicrobial prophylaxis with either trimethoprim-sulfamethoxazole or a fluoroquinolone. In some patients with cancer and neutropenia who develop viridans streptococcal bacteremia, a toxic shock–like syndrome has been described; Streptococcus mitis has been the causative species in most cases. Because resistance of viridans streptococci to a variety of antimicrobial agents is increasingly recognized, penicillin susceptibility cannot be assumed, and empirical vancomycin therapy should be used to treat neutropenic patients with cancer who have shock or are developing acute respiratory distress syndrome. Given the seriousness of septicemia caused by viridans streptococci and the potential for selection of other resistant microorganisms, the routine practice of antimicrobial prophylaxis for neutropenic patients with cancer should be reconsidered.




December 26, 2008 at 5:09 pm Leave a comment

Linezolid and Serotonergic Drug Interactions: A Retrospective Survey

Clinical Infectious Diseases  15 July 2006  V.43  N.2  p.180-187

Jeremy J. Taylor,2,a John W. Wilson,1 and Lynn L. Estes2

1Division of Infectious Diseases and 2Department of Pharmacy, Mayo Clinic, Rochester, Minnesota

Background.  Linezolid is a reversible, nonselective monoamine oxidase inhibitor. There are currently 11 published case reports of serotonin syndrome being associated with linezolid and selective serotonin reuptake inhibitors (SSRIs). Controversy exists regarding whether linezolid and SSRIs can be given concomitantly. The purpose of this study was to report the incidence of serotonin syndrome in patients receiving linezolid and SSRIs.

Methods.  This study was a retrospective chart review of inpatients at the Mayo Clinic (Rochester, MN) with concomitant orders or therapy within 14 days for linezolid and an SSRI from 2000 to 2004. The Sternbach criteria and Boyer criteria for diagnosis of serotonin syndrome were used to identify clinical features of serotonin syndrome.

Results.  Seventy-two patients received linezolid and an SSRI or venlafaxine within 14 days of each other. Fifty-two patients (72%) received concomitant therapy with linezolid and an SSRI or venlafaxine, and 20 patients (28%) did not receive concomitant therapy but received linezolid and an SSRI within a 14-day period. Overall, only 2 patients (3%) had a high probability of serotonin syndrome. In both patients with high probability, symptoms reversed rapidly on discontinuation of serotonergic therapy. The Boyer criteria were much more specific than the Sternbach criteria for identification of serotonin syndrome.

Conclusions.  On the basis of our experience, we suggest that, if the clinical situation warrants use of linezolid in a patient receiving an SSRI, linezolid may be used concomitantly with SSRIs, without a 14-day washout period and with careful monitoring for signs and symptoms of serotonin syndrome. Serotonergic agents should be promptly discontinued if serotonin syndrome is suspected.




December 26, 2008 at 5:00 pm Leave a comment

Comparison of Ampicillin-Sulbactam and Imipenem-Cilastatin for the Treatment of Acinetobacter Ventilator-Associated Pneumonia

Clinical Infectious Diseases  1 Jun 2002  V.34  N.11  p.1425-1430

G. Christopher Wood,1 Scott D. Hanes,1 Martin A. Croce,2 Timothy C. Fabian,2 and Bradley A. Boucher1

1Department of Clinical Pharmacy, The University of Tennessee College of Pharmacy, and 2Department of Surgery, University of Tennessee College of Medicine, Memphis

Acinetobacter organisms, which are a common cause of ventilator-associated pneumonia (VAP) in some health care centers, are becoming more resistant to such first-line agents as imipenem-cilastatin (Imi-Cil). Sulbactam has good in vitro activity against Acinetobacter organisms; thus, ampicillin-sulbactam (Amp-Sulb) may be a viable treatment alternative. The outcomes for critically ill trauma patients with Acinetobacter VAP treated with either Amp-Sulb or Imi-Cil were compared retrospectively. A total of 77 episodes in 75 patients were studied. Fourteen patients were treated with Amp-Sulb, and 63 patients were treated with Imi-Cil. Treatment efficacy was similar in the Amp-Sulb and Imi-Cil groups (93% vs. 83%, respectively;  ). No statistically significant differences between groups were noted with regard to associated mortality, duration of mechanical ventilation, or length of stay in the intensive care unit or hospital. However, adjunctive aminoglycoside therapy was used more often in the Amp-Sulb group. Patients generally received Amp-Sulb because of imipenem resistance. Amp-Sulb was effective in treating a small number of patients with Acinetobacter VAP; however, more data are needed.




December 25, 2008 at 10:12 pm Leave a comment

Reappraisal of Community-Acquired Bacteremia: A Proposal of a New Classification for the Spectrum of Acquisition of Bacteremia

Clinical Infectious Diseases  1 Jun 2002  V.34  N.11  p.1431-1439

Yardena Siegman-Igra,1 Boaz Fourer,1 Ruth Orni-Wasserlauf,1 Yoav Golan,1 Aliza Noy,1 David Schwartz,2 and Michael Giladi1,2

1Infectious Diseases Unit and 2Microbiology Laboratory, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Israel

In recent years, dramatic changes in health care systems have shifted much of the care of sick individuals from hospitals to the community. Consequently, infections traditionally classified as community-acquired or hospital-acquired infections cannot now be readily classified into either category. We thus propose a new classification based on a wider spectrum of acquisition. A total of 1028 episodes of bloodstream infection (BSI) were divided into 5 categories: true community-acquired infections (370 episodes [36%]), infections in recently discharged patients (110 [11%]), infections associated with invasive procedures performed just before or at the time of admission (56 [5%]), infections in patients admitted from nursing homes (68 [7%]), and hospital-acquired infections (424 [41%]). Thus, 234 (39%) of the 604 bloodstream infections traditionally defined as community acquired were reclassified into 3 newly defined groups, each of which has distinct epidemiologic, clinical, and bacteriologic characteristics, as well as distinct antimicrobial susceptibility profiles. There is a conceptual and practical need for such a new classification.




December 25, 2008 at 10:02 pm Leave a comment

Community-Acquired Methicillin-Resistant Staphylococcus aureus: A Meta-Analysis of Prevalence and Risk Factors

Clinical Infectious Diseases  15 January 2003  V.36  N.2  p.131-139

Cassandra D. Salgado, Barry M. Farr, and David P. Calfee

University of Virginia Health System, Charlottesville

Reports suggest that carriage of methicillin-resistant Staphylococcus aureus (MRSA) among persons without health care–associated risks has increased. A meta-analysis of studies reporting the prevalence of community-acquired MRSA (CA-MRSA) among MRSA isolates from hospitalized patients or the prevalence of MRSA colonization among community members was conducted. The CA-MRSA prevalence among hospital MRSA was 30.2% in 27 retrospective studies and 37.3% in 5 prospective studies; 85% of all patients with CA-MRSA had 1 health care–associated risk. The pooled MRSA colonization rate among community members was 1.3% (95% confidence interval [CI], 1.04%–1.53%), but there was significant heterogeneity among study populations. Community members from whom samples were obtained in health care facilities were more likely to be carrying MRSA than were community members from whom samples were obtained outside of the health care setting (relative risk, 2.35; 95% CI, 1.56–3.53). Among studies that excluded persons with health care contacts, the MRSA prevalence was 0.2%. Moreover, most persons with CA-MRSA had 1 health care–associated risk, which suggests that the prevalence of MRSA among persons without risks remains low (0.24%). Effective control of dissemination of MRSA throughout the community likely will require effective control of nosocomial MRSA transmission.




December 25, 2008 at 9:52 pm Leave a comment

The Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-Structure Infections

Clinical Infectious Diseases  15 June 2004  V.38  N.12  p.1673-1681

Robert D. Arbeit,1,a Dennis Maki,2 Francis P. Tally,1 Edward Campanaro,1 Barry I. Eisenstein,1 and the Daptomycin 98-01 and 99-01 Investigators

1Cubist Pharmaceuticals, Lexington, Massachusetts; and 2University of Wisconsin Medical School, Madison

Daptomycin is the first available agent from a new class of antibiotics, the cyclic lipopeptides, that has activity against a broad range of gram-positive pathogens, including organisms that are resistant to methicillin, vancomycin, and other currently available agents. Daptomycin (4 mg/kg intravenously [iv] every 24 h for 7–14 days) was compared with conventional antibiotics (penicillinase-resistant penicillins [4–12 g iv per day] or vancomycin [1 g iv every 12 h]) in 2 randomized, international trials involving 1092 patients with complicated skin and skin-structure infections. Among 902 clinically evaluable patients, clinical success rates were 83.4% and 84.2% for the daptomycin- and comparator-treated groups, respectively (95% confidence interval, −4.0 to 5.6). Among patients successfully treated with iv daptomycin, 63% required only 4–7 days of therapy, compared with 33% of comparator-treated patients ( ). The frequency and distribution of adverse events were similar among both treatment groups. Overall, the safety and efficacy of daptomycin were comparable with conventional therapy.




December 25, 2008 at 9:46 pm Leave a comment

Antimicrobial Prophylaxis for Surgery: An Advisory Statement from the National Surgical Infection Prevention Project

Clinical Infectious Diseases  15 June 2004  V.38  N.12  p.1706-1715

Dale W. Bratzler1 and Peter M. Houck,2 for the Surgical Infection Prevention Guidelines Writers Workgroupa

Oklahoma Foundation for Medical Quality, Oklahoma City, Oklahoma; and Centers for Medicare and Medicaid Services, Seattle, Washington

In January 2003, leadership of the Medicare National Surgical Infection Prevention Project hosted the Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW) meeting. The objectives were to review areas of agreement among the most-recently published guidelines for surgical antimicrobial prophylaxis, to address inconsistencies, and to discuss issues not currently addressed. The participants included authors from most of the groups that have published North American guidelines for antimicrobial prophylaxis, as well as authors from several specialty colleges. Nominal group process was used to draft a consensus paper that was widely circulated for comment. The consensus positions of SIPGWW include that infusion of the first antimicrobial dose should begin within 60 min before surgical incision and that prophylactic antimicrobials should be discontinued within 24 h after the end of surgery. This advisory statement provides an overview of other issues related to antimicrobial prophylaxis, including specific suggestions regarding antimicrobial selection.






December 25, 2008 at 9:38 pm Leave a comment

Tigecycline: A New Glycylcycline for Treatment of Serious Infections

Clin Infect Diseases 1 Sept 2005 V.41 N.S5 S303–S314   

Gary A. Noskin

Department of Medicine, Northwestern University, Feinberg School of Medicine, and Division of Infectious Diseases, Northwestern Memorial Hospital, Chicago, Illinois  

Tigecycline is a new semisynthetic glycylcycline for the treatment of serious infections. Of the glycylcyclines, tigecycline is the most studied and appears to hold promise as a new antimicrobial agent that can be administered as monotherapy to patients with many types of serious bacterial infections. For patients with serious infections, the initial choice for empirical therapy with broad-spectrum antibiotics is crucial, and, if the choice is inappropriate, it may have adverse consequences for the patient. Tigecycline has been designed to overcome many existing mechanisms of resistance among bacteria and confers broad antibiotic coverage against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and many species of multidrug-resistant gram-negative bacteria. Tigecycline has been efficacious and well tolerated in human clinical phase 2 studies, which warranted further evaluation of tigecycline in larger studies for treatment of many indications, including complicated skin and skin-structure infections, complicated intra-abdominal infections, and infections of the lower respiratory tract.  



December 24, 2008 at 6:15 pm Leave a comment

The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data.

Clin Infect Diseases 1 Sept 2005 V.41 NS5 S354-67

Timothy Babinchak,1 Evelyn Ellis-Grosse,1 Nathalie Dartois,2 Gilbert M. Rose,1 and Evan Loh,1 for theTigecycline 301 and 306 Study Groupsa

1Medical Research Group, Wyeth Research, Collegeville, Pennsylvania; 2Wyeth, Paris, FranceBabinchak T, Ellis-Grosse E, Dartois N, et al.

This pooled analysis includes 2 phase 3, double-blind trials designed to evaluate the safety and efficacy of tigecycline, versus that of imipenem-cilastatin, in 1642 adults with complicated intra-abdominal infections. Patients were randomized to receive either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 h) or imipenem-cilastatin (500/500 mg intravenously every 6 h) for 5–14 days. The primary end point was the clinical response at the test-of-cure visit (12–42 days after therapy) in the co-primary end point microbiologically evaluable and microbiological modified intent-to-treat populations. For the microbiologically evaluable group, clinical cure rates were 86.1% (441/512) for tigecycline, versus 86.2% (442/513) for imipenem-cilastatin (95% confidence interval for the difference, −4.5% to 4.4%; for noninferiority). Clinical cure rates in the microbiological modified intent-to-treat population were 80.2% (506/631) for tigecycline, versus 81.5% (514/631) for imipenem-cilastatin (95% confidence interval for the difference, −5.8% to 3.2%; for noninferiority). Nausea (24.4% tigecycline, 19.0% imipenem-cilastatin [ ]), vomiting (19.2% tigecycline, 14.3% imipenem-cilastatin [ ]), and diarrhea (13.8% tigecycline, 13.2% imipenem-cilastatin [ ) were the most frequently reported adverse events. This pooled analysis demonstrates that tigecycline was efficacious and well tolerated in the treatment of patients with complicated intra-abdominal infections.



December 24, 2008 at 6:14 pm Leave a comment

The Efficacy and Safety of Tigecycline in the Treatment of Skin and Skin-Structure Infections: Results of 2 Double-Blind Phase 3 Comparison Studies with Vancomycin-Aztreonam

Clin Infect Diseases 1 Sept 2005 V.41 N.S5 S341-53

E. J. Ellis-Grosse,1 T. Babinchak,1 N. Dartois,2 G. Rose,1 and E. Loh,1 for the

Tigecycline 300 and 305 cSSSI Study Groupsa

1Medical Research Group, Wyeth Research, Collegeville, Pennsylvania; 2Wyeth, Paris, France

Two phase 3, double-blind studies in hospitalized adults with complicated skin and skin-structure infections (cSSSI) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam. Patients received tigecycline (100 mg, followed by 50 mg intravenously twice daily) or vancomycin (1 g intravenously twice daily) plus aztreonam (2 g intravenously twice daily) for up to 14 days. Populations were as follows: 1116 patients (566 treated with tigecycline, and 550 treated with vancomycin-aztreonam) constituted the modified intent-to-treat (mITT) population, 1057 patients (538 treated with tigecycline, and 519 treated with vancomycin-aztreonam) constituted the clinical mITT (c-mITT) population, and 833 patients (422 treated with tigecycline, and 411 treated with vancomycin-aztreonam) constituted the clinically evaluable population. Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar: c-mITT, 79.7% (95% confidence interval [CI], 76.1%–83.1%) versus 81.9% (95% CI, 78.3%–85.1%) ( ); and clinically evaluable, 86.5% (95% CI, 82.9%–89.6%) versus 88.6% (95% CI, 85.1%–91.5%) ( ). Adverse events were similar, with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group. Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI.



December 24, 2008 at 6:12 pm Leave a comment

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