Archive for December, 2015

Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection

N Engl J Med 2015 Dec 24; V.373  N.26 P.2512-2521

William M. Geisler, M.D., M.P.H., Apurva Uniyal, M.A., Jeannette Y. Lee, Ph.D., Shelly Y. Lensing, M.S., Shacondra Johnson, B.S.P.H., Raymond C.W. Perry, M.D., M.S.H.S., Carmel M. Kadrnka, D.O., and Peter R. Kerndt, M.D., M.P.H.

From the Department of Medicine, University of Alabama at Birmingham, Birmingham (W.M.G.); the Departments of Preventive Medicine (A.U., P.R.K.) and Internal Medicine (P.R.K), University of Southern California, and Los Angeles County Department of Health Services, Juvenile Court Health Services  R.C.W.P., C.M.K.) — both in Los Angeles; the Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock (J.Y.L., S.Y.L.); and FHI 360, Durham, NC (S.J.). Address reprint requests to Dr. Geisler at the University of Alabama at Birmingham, 703 19th St. S., 242 Zeigler Research Bldg., Birmingham, AL 35294-0007, or at wgeisler@uab.edu.  

BACKGROUND

Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial reproductive morbidity. Recent studies have raised concern about the efficacy of azithromycin for the treatment of chlamydia infection.

METHODS

We conducted a randomized trial comparing oral azithromycin with doxycycline for the treatment of urogenital chlamydia infection among adolescents in youth correctional facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline (100 mg twice daily for 7 days). The treatment was directly observed. The primary end point was treatment failure at 28 days after treatment initiation, with treatment failure determined on the basis of nucleic acid amplification testing, sexual history, and outer membrane protein A (OmpA) genotyping of C. trachomatis strains.

RESULTS

Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin, and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each treatment group (65% male) made up the per-protocol population. There were no treatment failures in the doxycycline group. In the azithromycin group, treatment failure occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed difference in failure rates between the treatment groups was 3.2 percentage points, with an upper boundary of the 90% confidence interval of 5.9 percentage points, which exceeded the prespecified absolute 5-percentage-point cutoff for establishing the noninferiority of azithromycin.

CONCLUSIONS

In the context of a closed population receiving directly observed treatment for urogenital chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline was 100%. The noninferiority of azithromycin was not established in this setting. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00980148.)

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http://www.nejm.org/doi/pdf/10.1056/NEJMoa1502599

 

EDITORIAL

Treatment for Chlamydia Infection — Doxycycline versus Azithromycin

Thomas C. Quinn, M.D., and Charlotte A. Gaydos, Dr.P.H.

From the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (T.C.Q.), and the Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore (T.C.Q., C.A.G.) — both in Maryland.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection in the United States. In 2013, a total of 1.4 million cases were reported, and 3 million persons were estimated to be infected. Worldwide, 131 million persons are estimated to be infected with C. trachomatis. Untreated infections in women can result in pelvic inflammatory disease, infertility, ectopic pregnancy, and chronic pelvic pain. In men, the infection can be associated with urethritis, epididymitis, and, in men who have sex with men, proctitis. The Centers for Disease Control and Prevention (CDC) recommends that all sexually active women younger than 25 years of age undergo annual chlamydia screening.1 However, less than half of women 16 to 24 years of age who are enrolled in medical care programs were screened in 2013…..

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December 24, 2015 at 8:18 am

Infection Prevention and Evaluation of Fever After Laparoscopic Hysterectomy.

JSLS. 2015 Jul-Sep;19(3). pii: e2015.00065.

Lachiewicz MP, Moulton LJ, Jaiyeoba O.

Abstract

BACKGROUND:

Surgical site infection (SSI) is a common complication of hysterectomy. Minimally invasive hysterectomy has lower infection rates than abdominal hysterectomy. The lower SSI rates reflect the role and benefit in infection control of having minimal incisions, rather than a large anterior abdominal wall incision. Despite the lower rates, SSI after laparoscopic hysterectomy is not uncommon.In this article, we review pre-, intra-, and postoperative risk factors for infection. Rates of postoperative fever after laparoscopic hysterectomy and when evaluation for infection is warranted in a febrile patient are also reviewed.

DATABASE:

PubMed was searched for English-only articles using National Library of Medicine Medical Subject Headings(MESH) terms and keywords including but not limited to “postoperative,” “surgical site,” “infection,” “fever,” “laparoscopic,” “laparoscopy,” and “hysterectomy.”

CONCLUSIONS:

Reducing hospital-acquired infections such as SSI is one of the more effective ways of improving patient safety. Knowledge and understanding of risk factors for infection following laparoscopic hysterectomy enable the gynecologic surgeon or hospital to implement targeted preventive measures.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539492/pdf/e2015.00065.pdf

December 22, 2015 at 3:13 pm

Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim–sulfamethoxazole: Lessons from an observational cohort study.

Infection 2015 Oct 15

Dina Creemers-Schild, Frank P. Kroon, Ed. J. Kuijper, Mark G. J. de Boer

Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands

Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands

Background

The recommended treatment of Pneumocystis jirovecii pneumonia (PCP) is high-dose trimethoprim–sulfamethoxazole (TMP–SMX) in an equivalent of TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day for 2 or 3 weeks. High rates of adverse events are reported with this dose, which raises the question if lower doses are possible.

Methods

All adult patients diagnosed with PCP in various immune dysfunctions and treated with TMP–SMX between January 1, 2003 and July 1, 2013 in a tertiary university hospital were included. Per institutional protocol, patients initiated treatment on intermediate-dose TMP–SMX (TMP 10–15 mg/kg/day) and could be stepped down to low-dose TMP–SMX (TMP 4–6 mg/kg/day) during treatment. Clinical variables at presentation, relapse rate and mortality rates were compared between intermediate- and step-down treatment groups by uni- and multivariate analyses.

Results

A total of 104 patients were included. Twenty-four patients (23 %) were switched to low-dose TMP–SMX after a median of 4.5 days (IQR 2.8–7.0 days). One relapse (4 %) occurred in the step-down group versus none in the intermediate-dose group. The overall 30-day mortality was 13 %. There was 1 death in the step-down group (4 %) compared to 13 deaths (16 %) in the intermediate-dose group.

Conclusions

We observed high cure rates of PCP by treatment with intermediate-dose TMP–SMX. In addition, a step-down strategy to low-dose TMP–SMX during treatment in selected patients appears to be safe and does not compromise the outcome of treatment.

abstract

http://link.springer.com/article/10.1007%2Fs15010-015-0851-1

PDF

http://download.springer.com/static/pdf/174/art%253A10.1007%252Fs15010-015-0851-1.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs15010-015-0851-1&token2=exp=1450784605~acl=%2Fstatic%2Fpdf%2F174%2Fart%25253A10.1007%25252Fs15010-015-0851-1.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs15010-015-0851-1*~hmac=631be9d6e6d51a6cab7261bbad2f902231fc812d7b9685ea6777ac3747563a2c

December 22, 2015 at 8:31 am

Telavancin Hospital-Acquired Pneumonia Trials: Impact of Gram-Negative Infections and Inadequate Gram-Negative Coverage on Clinical Efficacy and All-Cause Mortality

Clinical Infectious Diseases SEP 15, 2015 V.61 Suppl.2 S87-S93

Melinda K. Lacy, Martin E. Stryjewski, Whedy Wang, Thomas C. Hardin, Boris Nogid, David R. Luke, Andrew F. Shorr, G. Ralph Corey, and Steven L. Barriere

1Theravance Biopharma US, South San Francisco, California

2Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Ciudad Autónoma de Buenos Aires, Argentina

3Pulmonary and Critical Care Medicine, Washington Hospital Center, Washington D.C

4Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina

Correspondence: Melinda K. Lacy, PharmD, Theravance Biopharma US, 901 Gateway Blvd, S San Francisco, CA 94080 (mlacy@theravance.com).

Background

When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia).

Methods

This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive–only infections, (2) gram-positive–only and mixed infections-adequate GNC, and (3) gram-negative–only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin.

Results/Conclusions

In the ATTAIN safety population there were 16 more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative–only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups.

PDF

http://cid.oxfordjournals.org/content/61/suppl_2/S87.full.pdf

December 20, 2015 at 4:54 pm

The Role of Telavancin in Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia

Clinical Infectious Diseases SEP 15, 2015 V.61 Suppl.2 S79-S86

Christian E. Sandrock and Andrew F. Shorr

1Division of Pulmonary and Critical Care, University of California Davis School of Medicine, Sacramento

2Department of Pulmonary and Critical Care, Washington Hospital Center, Washington D.C

Correspondence: Christian E. Sandrock, MD, MPH, FCCP, UC Davis Medical Group–Davis, 4150 V St #3400, Sacramento, CA 95817 (cesandrock@ucdavis.edu).

Hospital-acquired pneumonia (HAP) due to gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause of morbid conditions and death. Telavancin is a lipoglycopeptide antibiotic with potent in vitro activity against a range of gram-positive pathogens, including MRSA, methicillin-susceptible S. aureus, and Streptococcus species. In 2 phase 3 clinical trials, telavancin was noninferior to vancomycin in patients with HAP due to gram-positive pathogens. Clinically evaluable patients with S. aureus as the sole pathogen or S. aureus with a vancomycin minimum inhibitory concentration >1 µg/mL, however, had higher cure rates with telavancin than with vancomycin. In patients with bacteremic HAP, telavancin resulted in clearance of blood cultures. It was associated with increased serum creatinine levels and higher mortality rates in patients with moderate to severe renal impairment at baseline; however, on subsequent analysis, the outcomes seemed to have been at least partially affected by the adequacy of empiric gram-negative antimicrobial therapy. Thus, clinicians need to consider the risk-benefit balance when choosing telavancin in patients with severe renal impairment at baseline. Overall, these data support the use of telavancin in the treatment of HAP due to S. aureus, including MRSA and strains with elevated vancomycin minimum inhibitory concentrations, but clinicians should always weigh the risks and benefits of various treatment options.

PDF

http://cid.oxfordjournals.org/content/61/suppl_2/S79.full.pdf

December 20, 2015 at 4:52 pm

Skin and Soft-Tissue Infections: A Critical Review and the Role of Telavancin in Their Treatment

Clinical Infectious Diseases SEP 15, 2015 V.61 Suppl.2 S69-S78

Amilcar F. Cardona and Samuel E. Wilson

Department of Surgery, University of California, Irvine

Correspondence: Samuel E. Wilson, MD, FACS, Department of Surgery, University of California, Irvine, Medical Center, City Tower, Ste 810, 333 City Blvd W, Orange, CA 92868-3298 (wilsonse@uci.edu).

Skin and soft-tissue infections (SSTIs) are an important cause of morbidity and mortality among hospitalized patients and a major therapeutic challenge for clinicians. Although uncomplicated SSTIs are managed successfully on an outpatient basis, more serious infections extending to the subcutaneous tissue, fascia, or muscle require complex management. Early diagnosis, selection of appropriate antimicrobials, and timely surgical intervention are key to successful treatment. Surgical-site infections, an important category of SSTI, occur in approximately half a million patients in North America annually. SSTIs are also a potential source for life-threatening bacteremia and metastatic abscesses. Gram-positive organisms, such as Staphylococcus aureus and Streptococcus pyogenes, are the dominant organisms isolated early in the infectious process, whereas gram-negative organisms are found in chronic wounds. Methicillin-resistant S. aureus (MRSA) is a potential bloodstream invader that requires aggressive antimicrobial treatment and surgery. Recent concerns regarding vancomycin activity include heteroresistance in MRSA and increase in the minimum inhibitory concentrations (>1 or 2 µg/mL); however, alternative agents, such as telavancin, daptomycin, linezolid, ceftaroline, dalbavancin, oritavancin, and tedizolid, are now available for the treatment of severe MRSA infections. Here, we present a review of the epidemiology, etiology, and available treatment options for the management of SSTIs.

PDF

http://cid.oxfordjournals.org/content/61/suppl_2/S69.full.pdf

December 20, 2015 at 4:51 pm

Telavancin: Mechanisms of Action, In Vitro Activity, and Mechanisms of Resistance

Clinical Infectious Diseases SEP 15, 2015 V.61 Suppl.2 S58-S68

James A. Karlowsky, Kim Nichol, and George G. Zhanel

1Department of Medical Microbiology, College of Medicine, University of Manitoba

2Diagnostic Services Manitoba, Winnipeg, Canada

Correspondence: George G. Zhanel, PhD, Clinical Microbiology, Health Sciences Centre, MS673-820 Sherbrook St, Winnipeg, Manitoba R3A 1R9, Canada (ggzhanel@pcs.mb.ca).

Telavancin is a semisynthetic lipoglycopeptide derivative of vancomycin. Telavancin has a dual mechanism of antibacterial action, disrupting peptidoglycan synthesis and cell membrane function. In 2014, the Clinical and Laboratory Standards Institute (CLSI) revised the antimicrobial susceptibility testing method for telavancin, resulting in minimum inhibitory concentration (MIC) determinations that are more accurate and reproducible and demonstrate greater in vitro potency than shown with the previous testing method. The CLSI testing method changes coincided with revised telavancin MIC interpretive break point criteria for susceptibility approved by the US Food and Drug Administration for Staphylococcus aureus (≤0.12 µg/mL), Streptococcus pyogenes (≤0.12 µg/mL), Streptococcus agalactiae (≤0.12 µg/mL), Streptococcus anginosus group (≤0.06 µg/mL), and Enterococcus faecalis (vancomycin susceptible, ≤0.25 µg/mL). Telavancin is equally potent against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). It demonstrates activity against isolates of heterogeneous vancomycin-intermediate S. aureus and vancomycin-intermediate S. aureus but is poorly active against vancomycin-resistant S. aureus. It also demonstrates potent activity against Staphylococcus epidermidis and Streptococcus spp. (MIC90 ≤0.03 µg/mL). Thus far, it has not been possible to select for high-level telavancin resistance in the laboratory using serially passaged clinical isolates of MRSA and MSSA.

PDF

http://cid.oxfordjournals.org/content/61/suppl_2/S58.full.pdf

December 20, 2015 at 4:49 pm

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