Original Investigation – Neutropenia in Human Immunodeficiency Virus Infection

Source: Archives of Internal Medicine Vol.166 N.4 Feb 27, 2006 p.405-410

Data From the Women’s Interagency HIV Study

Alexandra M. Levine, MD; Roksana Karim, MBBS, MS; Wendy Mack, PhD; D. Jay Gravink, MA; Katherine Anastos, MD; Mary Young, MD; Mardge Cohen, MD; Meg Newman, MD; Michael Augenbraun, MD; Stephen Gange, PhD; D. Heather Watts, MD

Background:  Neutropenia is well described in individuals infected with human immunodeficiency virus (HIV) and occurs in approximately 10% to 50% of cases. Neither the effect of highly active antiretroviral therapy (HAART) on neutrophil counts nor the significance of neutropenia in terms of survival has previously been evaluated.

Methods:  The prevalence of neutropenia among 1729 HIV-infected women, followed up as part of the Women’s Interagency HIV Study, was evaluated. The CD4 lymphocyte counts, HIV-1 RNA levels, and complete blood cell counts, including absolute neutrophil counts, were obtained at 6-month intervals.

Results:  Neutropenia was common among HIV-infected women; at baseline, 44% had neutrophil counts less than 2000/µL, whereas 7% had counts less than 1000/µL. During 7.5 years of follow-up, neutrophil counts less than 2000/µL occurred on at least 1 occasion in 79%, whereas absolute neutrophil counts less than 1000/µL were documented in 31%. Worsening HIV disease parameters, such as lower CD4 cell counts (PConclusions:  Worsening HIV disease parameters are associated with neutropenia in HIV-infected women. Treatment with HAART, without zidovudine in the regimen, protects against development of neutropenia, whereas HAART use and higher CD4 cell counts are associated with resolution of neutropenia. Neutropenia is not associated with decreased survival in HIV-infected women.

Author Affiliations: Department of Medicine, Division of Hematology (Dr Levine and Mr Gravink), and Department of Preventive Medicine, Division of Biostatistics (Drs Karim and Mack), Keck School of Medicine, University of Southern California, Los Angeles; Department of Medicine, Montefiore Medical Center, Bronx, NY (Dr Anastos); Department of Medicine, Georgetown University School of Medicine, Washington, DC (Dr Young); Care Center, Cook County Bureau of Health Services, Department of Medicine, Rush Medical College, Chicago, Ill (Dr Cohen); Department of Medicine, Division of AIDS, San Francisco General Hospital, University of California School of Medicine, San Francisco (Dr Newman); Department of Medicine, Maimonides Medical Center and State University of New York, Health Sciences Center at Brooklyn, Brooklyn, NY (Dr Augenbraun); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md (Dr Gange); and the Pediatric, Adolescent, and Maternal AIDS Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Rockville, Md (Dr Watts).

BRIEF REPORT – Repeat Infective Endocarditis: Differentiating Relapse from Reinfection

Source: Clinical Infectious Diseases 1 Aug 2005 vol.41 N.3 p.406-409

Vivian H. Chu,1,2 Daniel J. Sexton,1 Christopher H. Cabell,1,2 L. Barth Reller,1,4 Paul A. Pappas,2 Rakesh K. Singh,3 Vance G. Fowler, Jr.,1,2 G. Ralph Corey,1,2 Olcay Aksoy,3 and Christopher W. Woods1,2,5

1Department of Medicine, 2Duke Clinical Research Institute, 3School of Medicine, and 4Clinical Microbiology Laboratory, Duke University Medical Center, and 5Clinical Microbiology Laboratory, Durham Veterans Affairs Medical Center, Durham, North Carolina

Repeat infective endocarditis due to the same species can represent relapse of the initial infection or a new infection. We used time-based clinical criteria and pulsed-field gel electrophoresisbased molecular criteria to classify 13 cases of repeat infective endocarditis as either relapse or reinfection. The agreement between clinical and molecular criteria was imperfect (agreement in 10 [77%] of 13 cases).

MAJOR ARTICLE – Hospital-Acquired Invasive Group A Streptococcal Infections in Ontario, Canada, 19922000

Source: Clinical Infectious Diseases 1 Aug 2005 vol.41 N.3 p.334-342

N. Daneman,1 A. McGeer,1,2 D. E. Low,1,2 G. Tyrrell,6 A. E. Simor,1,3 M. McArthur,2 B. Schwartz,7 P. Jessamine,5 R. Croxford,4 and K. A. Green,2 for the Ontario Group A Streptococcal Study Group

1University of Toronto, 2Mount Sinai Hospital, 3Sunnybrook & Women’s College Health Sciences Centre, and 4Institute for Clinical Evaluative Science, Toronto, and 5Ottawa Hospital and University of Ottawa, Ontario; 6National Centre for Streptococcus, Edmonton, Alberta; and 7Centers for Disease Control and Prevention, Atlanta, Georgia

Background. A significant proportion of invasive group A streptococcal infections are hospital acquired. No large, prospective studies have characterized this subgroup of cases and evaluated the risk of transmission in hospitals.

Methods. We conducted prospective, population-based surveillance of invasive group A streptococcal infections in Ontario, Canada, from 1992 to 2000. Epidemiologic and microbiologic investigations were conducted to identify cross-transmission.

Results. We identified 291 hospital-acquired cases (12.4%) among 2351 cases of invasive group A streptococcal disease. Hospital-acquired invasive group A streptococcal infections are heterogeneous, including surgical site (96 cases), postpartum (86 cases), and nonsurgical, nonobstetrical infections (109 cases). Surgical site infections affected 1 of 100,000 surgical procedures and involved all organ systems. Postpartum infections occurred at a rate of 0.7 cases per 10,000 live births and exhibited an excellent prognosis. Nonsurgical, nonobstetrical infections encompassed a broad range of infectious syndromes (case-fatality rate, 37%). Nine percent of cases were associated with in-hospital transmission. Transmission occurred from 3 of 142 patients with community-acquired cases of necrotizing fasciitis requiring intensive care unit (ICU) admission, compared with 1 of 367 patients with community-acquired cases without necrotizing fasciitis admitted to the ICU and 1 of 1551 patients with other cases (P Conclusions. Presentation of hospital-associated invasive group A streptococcal infections is diverse. Cross-transmission is common; illness occurs in patients but rarely in staff. Isolation of new cases of necrotizing fasciitis and intervention after a single nosocomial case may also prevent transmission.

MAJOR ARTICLE – Comparison of Mortality Associated with Vancomycin-Resistant and Vancomycin-Susceptible Enterococcal Bloodstream Infections: A Meta-analysis

Source: Clinical Infectious Diseases 1 Aug 2005 vol.41 N.3 p.327-333

Carlos A. DiazGranados,1,3 Shanta M. Zimmer,1 Mitchel Klein,2 and John A. Jernigan1

1Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, and 2Rollins School of Public Health, Emory University, Atlanta, Georgia; and 3Research Division, Fundación Universitaria de Ciencias de la Salud School of Medicine, Bogota, Colombia

Background. Whether vancomycin resistance is independently associated with mortality among patients with enterococcal bloodstream infection (BSI) is controversial. To address this issue, we performed a systematic literature review with meta-analysis.

Methods. Data sources were studies identified using the MEDLINE database (for articles from 1988 through March 2003), the Cochrane Library (for articles published up to March 2003), and bibliographies of identified articles. Inclusion criteria were that the study assessed mortality after enterococcal BSI, compared mortality after vancomycin-resistant enterococci (VRE) BSI with that after vancomycin-susceptible enterococci (VSE) BSI, and adjusted for severity of illness. Study exclusion criteria were as follows: no report of the adjusted measure of effect (adjusted odds ratio [OR], adjusted hazard ratio, or adjusted relative risk) of vancomycin resistance on mortality available and/or its adjusted 95% confidence interval (95% CI). Data in the tables, figures, or text were independently extracted by 2 of the authors. Individual weights were calculated using the 95% CI of the adjusted measures of effect performing both fixed-effect and random-effects models.

Results. Nine studies were eligible (11 studies met the inclusion criteria, and 2 were excluded), with a total of 1614 enterococcal BSI episodes (683 VRE episodes and 931 VSE episodes). Patients with bacteremia caused by VRE were more likely to die than were those with VSE bacteremia (summary OR, 2.52; 95% CI, 1.93.4).

Conclusions. Vancomycin resistance is independently associated with increased mortality among patients with enterococcal bloodstream infection.

Presented in part: 41st Meeting of the Infectious Diseases Society of America, San Diego, California, October, 2003 (abstract 491).

MAJOR ARTICLE – Increased Risk of Common Infections in Patients with Type 1 and Type 2 Diabetes Mellitus

Source: Clinical Infectious Diseases 1 Aug 2005 vol.41 N.3 p.281-288

L. M. A. J. Muller,1 K. J. Gorter,1 E. Hak,1 W. L. Goudzwaard,1 F. G. Schellevis,3 A. I. M. Hoepelman,2 and G. E. H. M. Rutten1

1Julius Center for Health Sciences and Primary Care and 2Department of Medicine, Division of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, and 3Netherlands Institute for Health Services Research NIVEL, Utrecht, The Netherlands

Background. Clinical data on the association of diabetes mellitus with common infections are virtually lacking, not conclusive, and often biased. We intended to determine the relative risks of common infections in patients with type 1 and type 2 diabetes mellitus (DM1 and DM2, respectively).

Methods. In a 12-month prospective cohort study conducted as part of the Second Dutch National Survey of General Practice, we compared 705 adult patients who had DM1 and 6712 adult patients who had DM2 with 18,911 control patients who had hypertension without diabetes. Outcome measures were medically attended episodes of infection of the respiratory tract, urinary tract, and skin and mucous membranes. We applied multivariable and polytomous logistic regression analysis to determine independent risks of infections and their recurrences in patients with diabetes, compared with control patients.

Results. Upper respiratory infections were equally common among patients with diabetes and control patients. Patients with diabetes had a greater risk of lower respiratory tract infection (for patients with DM1: adjusted odds ratio [AOR], 1.42 [95% confidence interval {CI}, 0.962.08]; for patients with DM2: AOR, 1.32 [95% CI, 1.131.53]), urinary tract infection (for patients with DM1: AOR, 1.96 [95% CI, 1.492.58]; for patients with DM2: AOR, 1.24 [95% CI, 1.101.39]), bacterial skin and mucous membrane infection (for patients with DM1: AOR, 1.59 [95% CI, 1.122.24]; for patients with DM2: AOR, 1.33 [95% CI, 1.151.54]), and mycotic skin and mucous membrane infection (for patients with DM1: AOR, 1.34 [95% CI, 0.971.84]; for patients with DM2: AOR, 1.44 [95% CI, 1.271.63]). Risks increased with recurrences of common infections.

Conclusions. Patients with DM1 and DM2 are at increased risk for lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection. Studies are warranted into management of such infections in patients with diabetes.

HEALTHCARE EPIDEMIOLOGY INVITED ARTICLE – Control of Vancomycin-Resistant Enterococci: One Size Fits All?

Source: Clinical Infectious Diseases 15 Jul 2005 Vol.41 N.2 p.210-216

Robert. A. Weinstein, Section Editor

Emilian Armeanu1 and Marc J. M. Bonten2,3 1Rush University Medical Center, Chicago, Illinois, and 2Department of

Internal Medicine, Division of General Medicine & Infectious Diseases, Julius Center for Health Sciences and Primary Care, and 3Department of Hospital Hygiene and Infection Prevention, University Medical Center Utrecht, The Netherlands

Infection caused by vancomycin-resistant enterococci (VRE) is associated with high morbidity and mortality rates; it poses a serious threat, in particular, to immunosuppressed patients. It generates high costs and challenges infection-control programs. Here, we look at the insights that mathematical models offer into the epidemiology of VRE colonization and infection, the potential benefits of various infection-control interventions, and the possibility of designing a tailored approach to controlling VRE. Models show that epidemics of VRE infection in diverse institutions may differ in the relative contributions of cross-transmission and the influx of new cases, as well as in the various mechanisms of local transmission. They also highlight the phenomenon of decreasing returns associated with many interventions and, hence, the need to identify the most important routes of transmission, to break the weakest links in the chain of transmission, and to contain the influx of cases of VRE infection. These observations also provide insights into the management of infection with other antibiotic-resistant nosocomial pathogens.

MAJOR ARTICLE – Risk Factors for Colonization with Methicillin-Resistant Staphylococcus aureus (MRSA) in Patients Admitted to an Urban Hospital: Emergence of Community-Associated MRSA Nasal Carriage

Source: Clinical Infectious Diseases 15 Jul 2005 Vol.41 N.2 p.159-166

Alicia I. Hidron,1 Ekaterina V. Kourbatova,1 J. Sue Halvosa,2 Bianca J. Terrell,1 Linda K. McDougal,3 Fred C. Tenover,3 Henry M. Blumberg,1,2 and Mark D. King1,2

1Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 2Epidemiology Department, Grady Memorial Hospital, and 3Centers for Disease Control and Prevention, Atlanta, Georgia

Background. Surveillance cultures performed at hospital admission have been recommended to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) but require substantial resources. We determined the prevalence of and risk factors for MRSA colonization at the time of hospital admission among patients cared for at a public urban hospital.

Methods. Anterior nares cultures were obtained within 48 h after admission during a 1-month period. A case-control study and molecular typing studies were performed.

Results. A total of 53 (7.3%) of 726 patients had a nares culture positive for MRSA, and 119 (16.4%) had a nares culture that was positive for methicillin-susceptible S. aureus. In multivariate analysis, risk factors for MRSA colonization included antibiotic use within 3 months before admission (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.25.0), hospitalization during the past 12 months (OR, 4.0; 95% CI, 2.08.2), diagnosis of skin or soft-tissue infection at admission (OR, 3.4; 95% CI, 1.57.9), and HIV infection. A total of 47 (89%) of 53 case patients colonized with MRSA had at least 1 of these independent risk factors, in contrast to 343 (51%) of 673 control patients (OR, 7.5; 95% CI, 3.2 17.9). Molecular typing demonstrated that 16 (30%) of 53 MRSA nares isolates (2.2% of the 726 isolates) belonged to the USA300 community-associated MRSA (CA-MRSA) genotype.

Conclusion. The prevalence of MRSA colonization at the time of patient admission was high (>7%). Limiting surveillance cultures to patients with 1 of the identified risk factors may allow for targeted screening.

The emergence of CA-MRSA colonization represents a new, unrecognized reservoir of MRSA within hospitals, potentially increasing the risk for horizontal transmission.
 

MAJOR ARTICLE – Effect of Aminoglycoside and -Lactam Combination Therapy versus -Lactam Monotherapy on the Emergence of Antimicrobial Resistance: A Meta-analysis of Randomized, Controlled Trials

Source: Clinical Infectious Diseases 15 Jul 2005 Vol.41 N.2 p.149-158

Ioannis A. Bliziotis,1 George Samonis,3 Konstantinos Z. Vardakas,1

Stavroula Chrysanthopoulou,1 and Matthew E. Falagas1,2,4 1Alfa Institute of Biomedical Sciences (AIBS) and 2Department of Medicine, “Henry Dunant” Hospital, Athens, and 3Department of Medicine, University of Crete, School of Medicine, Iraklion, Greece; and 4Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts

Background. The addition of an aminoglycoside to a -lactam therapy regimen has been suggested to have a beneficial effect in delaying or preventing the development of antimicrobial resistance. We studied the effect of aminoglycoside/-lactam combination therapy versus -lactam monotherapy on the emergence of resistance.

Methods. We performed a meta-analysis of randomized, controlled trials (RCTs) that compared aminoglycoside/-lactam combination therapy with -lactam monotherapy and that reported data regarding the emergence of resistance (primary outcome) and/or development of superinfection, treatment failure, treatment failure attributable to emergence of resistance, treatment failure attributable to superinfection, all-cause mortality during treatment, and mortality due to infection. Data for this meta-analysis were identified from the PubMed database, Current Contents database, Cochrane central register of controlled trials, and references in relevant articles.

Results. A total of 8 RCTs were included in the analysis. -Lactam monotherapy was not associated with a greater emergence of resistance than was the aminoglycoside/-lactam combination (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.561.47). Actually, -lactam monotherapy was associated with fewer superinfections (OR, 0.62; 95% CI, 0.420.93) and fewer treatment failures (OR, 0.62; 95% CI, 0.381.01). Rates of treatment failure attributable to emergence of resistance (OR, 3.09; 95% CI, 0.7512.82), treatment failure attributable to superinfection (OR, 0.60; 95% CI, 0.331.10), all-cause mortality during treatment (OR, 0.70; 95% CI, 0.401.25), and mortality due to infection (OR, 0.74; 95% CI, 0.461.21) did not differ significantly between the 2 regimens.

Conclusions. Compared with -lactam monotherapy, the aminoglycoside/-lactam combination was not associated with a beneficial effect on the development of antimicrobial resistance among initially antimicrobial-susceptible isolates.

MAJOR ARTICLE – Antimicrobial Resistance among Streptococcus pneumoniae in the United States: Have We Begun to Turn the Corner on Resistance to Certain Antimicrobial Classes?

Source: Clinical Infectious Diseases 15 Jul 2005 Vol.41 N.2 p.139-148

Gary V. Doern, Sandra S. Richter, Ashley Miller, Norma Miller, Cassie Rice, Kristopher Heilmann and Susan Beekmann

Department of Pathology, University of Iowa College of Medicine, Iowa City

Background. Antimicrobial resistance has emerged as a major problem in Streptococcus pneumoniae in the United States during the past 15 years. This study was undertaken to elucidate the current scope and magnitude of this problem in the United States and to assess resistance trends since 1994-1995.

Methods. A total of 1817 S. pneumoniae isolates obtained from patients with community-acquired respiratory tract infections in 44 US medical centers were characterized during the winter of 2002-2003. The activity of 27 antimicrobial agents was assessed. In addition, selected isolates were examined for the presence of mutations in the quinolone-resistance determining regions (QRDRs) of parC and gyrA that resulted in diminished fluoroquinolone activity. The results of this survey were compared with the results of 4 previous surveys conducted in a similar manner since 1994-1995.

Results. Overall rates of resistance (defined as the rate of intermediate resistance plus the rate of resistance) were as follows: penicillin, 34.2%; ceftriaxone, 6.9%; erythromycin, 29.5%; clindamycin, 9.4%; tetracycline, 16.2%; and trimethoprim-sulfamethoxazole (TMP-SMX), 31.9%. No resistance was observed with vancomycin, linezolid, or telithromycin; 22.2% of isolates were multidrug resistant; 2.3% of isolates had ciprofloxacin MICs of 4.0 g/mL. It was estimated that 21.9% of the isolates in this national collection had mutations in the QRDRs of parC and/or gyrA, with parC only mutations occurring most often (in 21% of all isolates). Trend analysis since 19941995 indicated that rates of resistance to -lactams, macrolides, tetracyclines, TMP-SMX, and multiple drugs have either plateaued or have begun to decrease. Conversely, fluoroquinolone resistance among S. pneumoniae is becoming more prevalent.

Conclusion. It appears that, as fluoroquinolone resistance emerges among S. pneumoniae in the United States, resistance to other antimicrobial classes is becoming less common.

MAJOR ARTICLE – White Blood Cell Counts and Malaria

Source: Journal of Infectious Diseases 15 Jul 2005 Vol.192 N.2 p.323-330

F. Ellis McKenzie,1 Wendy A. Prudhomme,1 Alan J. Magill,2 J. Russ Forney,2 Barnyen Permpanich,3 Carmen Lucas,4 Robert A. Gasser, Jr.,2 and Chansuda Wongsrichanalai5

1Fogarty International Center, National Institutes of Health, Bethesda, and 2Walter Reed Army Institute of Research, Silver Spring, Maryland; 3Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; 4US Naval Medical Research Center Detachment, Lima, Peru; 5US Naval Medical Research Unit No. 2, Jakarta, Indonesia

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparuminfected patients were lower than those in the Plasmodium vivaxinfected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparuminfected patients had WBC counts of Financial support: US Army Medical Research and Materiel Command. The views presented here are those of the authors and are not to be taken to represent those of our respective institutions