Larry M. Baddour

Risk Factor Analysis of Permanent Pacemaker Infection

Background. Several host- and procedure-related factors have been reported to increase the risk of permanent pacemaker (PPM) infection on the basis of descriptive analyses of case series. The purpose of this study is to assess the risk factors for PPM infection using case-control study methods.Methods. All patients who had a PPM implanted at our institution from January 1991 to December 2003 were retrospectively reviewed. Each patient who experienced a PPM infection was matched with 2 control subjects by age, sex, year of implantation, and duration of follow-up. Univariate and multivariable analyses were performed to identify significant risk factors for PPM infection.Results. Twenty-nine case patients and 58 control subjects met inclusion criteria. The majority (83%) of case patients presented with a pocket infection; a minority (10%) had PPM-related endocarditis. Staphylococcus species (69%) were the most common pathogens. On univariate analysis, previous PPM infection, malignancy, long-term corticosteroid use, multiple device revisions, a permanent central venous catheter, the presence of >2 pacing leads, and a lack of antibiotic prophylaxis at the time of PPM placement were associated with an increased risk of PPM infection. A multivariable logistic regression model identified long-term corticosteroid use (odds ratio [OR], 13.90; 95% confidence interval [CI], 1.27-151.7; P=.03) and the presence of >2 pacing leads versus 2 leads (OR, 5.41; 95% CI, 1.44-20.29; P=.01) as independent risk factors for PPM infection. In contrast, use of antibiotic prophylaxis prior to PPM implantation had a protective effect (OR, 0.087; 95% CI, 0.016-0.48; P=.005).Conclusions. These findings should assist clinicians in identifying patients who are at increased risk of PPM infection, as well as in developing strategies to minimize the modifiable risks.

Temporal Trends in Permanent Pacemaker Implantation: A Population-Based Study

BACKGROUNDnLimited data exist regarding temporal trends in permanent pacemaker (PPM) implantation. To describe trends in incidence and comorbidities of PPM recipients, we conducted a retrospective population-based cohort study over a 30-year period.nnnMETHODSnAll 1291 adult residents of Olmsted County, Minnesota, undergoing PPM implantation between 1975 and 2004 were included in the study. Trends in PPM implantation incidence, pacing mode and indication, and comorbidities (via Charlson Comorbidity Index [CCI]) were assessed through the Rochester Epidemiology Project. Permanent pacemaker recipients were compared with age- and sex-matched PPM-free controls from the population.nnnRESULTSnAdjusted implantation incidence rates increased from 36.6 per 100,000 person-years during 1975 to 1979 to 99 per 100,000 person-years during 2000 to 2004 (P < .0001). After adjusting for age (hazard ratio [HR] 1.06 per year), male sex (HR 1.28), and implant year (HR 0.98), the HR for death among PPM recipients by CCI quartiles was 1.0, 1.79, 2.29, and 3.91 for CCI of 0 to 1 (reference), 2 to 3, 4 to 6, and > or = 7, respectively (P < .0001). Overall, PPM recipients had higher CCI than the population-based controls (P = .04), with higher mean CCI noted since 1990. Mean age-adjusted CCI increased from 3.15 to 4.60 among the cases (P < .0001) and from 3.06 to 3.54 among the age- and sex-matched controls (P = .047).nnnCONCLUSIONSnThere have been significant increases in incidence of PPM implantation over 30 years, and PPM recipients have had an age-independent increase in comorbidities relative to the underlying population, especially over the past 15 years.

Avian Influenza: A New Pandemic Threat?

n n In December 2003, the largest outbreak of highly pathogenic avian influenza H5N1 occurred among poultry in 8 Asian countries. A limited number of human H5N1 infections have been reported from Vietnam and Thailand, with a mortality rate approaching 70%. Deaths have occurred in otherwise healthy young individuals, which is reminiscent of the 1918 Spanish influenza pandemic. The main presenting features were fever, pneumonitis, lymphopenia, and diarrhea. Notably, sore throat, conjunctivitis, and coryza were absent. The H5N1 strains are resistant to amantadine and rimantadine but are susceptible to neuraminidase inhibitors, which can be used for treatment and prophylaxis. The widespread epidemic of avian influenza in domestic birds increases the likelihood for mutational events and genetic reassortment. The threat of a future pandemic from avian influenza is real. Adequate surveillance, development of vaccines, outbreak preparedness, and pandemic influenza planning are important. This article summarizes the current knowledge on avian influenza, including the virology, epidemiology, diagnosis, and management of this emerging disease.n n

Frequency of Permanent Pacemaker or Implantable Cardioverter-Defibrillator Infection in Patients with Gram-Negative Bacteremia

BACKGROUNDnDespite the frequent occurrence of bacteremia due to gram-negative organisms in patients with underlying permanent pacemakers (PPMs) or implantable cardioverter defibrillators (ICDs), the outcome and treatment of these patients has received scant attention. In patients with PPMs or ICDs who have Staphylococcus aureus bacteremia, 45% have PPM/ICD infection.nnnMETHODSnWe conducted a retrospective cohort study over a 7-year period to assess the clinical features and frequency of PPM/ICD infection in patients with gram-negative bacteremia, as well as the incidence of relapse in patients for whom the device was not removed.nnnRESULTSnForty-nine patients were included in the study; 3 (6%) had either definite (2 patients) or possible (1 patient) PPM/ICD infection. Both patients with definite PPM/ICD infection had clear infection of the generator pocket. None of the other patients with alternate sources of bacteremia developed PPM/ICD infection. Thirty-four patients with retained PPM/ICD were observed for >12 weeks (median time, 759 days), and 2 (6%) developed relapsing bacteremia, although they each had alternative sources of relapse.nnnCONCLUSIONSnIn sharp contrast to S. aureus infection, PPM/ICD infection in patients with gram-negative bacteremia was rare, and no patients appeared to have secondary PPM/ICD infection due to hematogenous seeding of the system. Despite infrequent system removal in these patients, relapsing bacteremia among patients who survived initial bacteremia was rarely seen. If secondary PPM/ICD infection occurs in patients with gram-negative bacteremia, it is either uncommon or it is cured with antimicrobial therapy despite device retention.

Impact of Prior Antiplatelet Therapy on Risk of Embolism in Infective Endocarditis

BACKGROUNDnEmbolism is a dreaded complication of infective endocarditis (IE). Currently, antimicrobial therapy is the only medical intervention proven to decrease the risk of embolism associated with IE. We hypothesized that, because platelet aggregation is operative in the pathogenesis of vegetation formation, embolism associated with IE should occur less frequently among patients who have received prior, continuous daily antiplatelet therapy for noninfectious reasons.nnnMETHODSnWe studied a retrospective cohort of adult patients with a diagnosis of IE who presented to the Mayo Clinic (Rochester, MN) during 1980-1998. The cohort was divided into 2 groups on the basis of whether they had received continuous daily antiplatelet therapy for at least 6 months prior to the time of hospitalization for IE. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine, or any of combination of these agents. The primary end point was a symptomatic embolic event that occurred prior to or during hospitalization. Multivariable logistic regression was used to assess the impact of continuous daily antiplatelet therapy on risk of symptomatic emboli associated with IE.nnnRESULTSnOne hundred forty-seven (24.5%) of 600 patients experienced a symptomatic embolic event; the most common embolic manifestation was stroke (in 48.2% of patients). Embolic events occurred significantly less often among those who had received prior, continuous daily antiplatelet therapy (12.0% of patients who had received therapy vs. 27.8% patients who had not receive therapy; P<.001). After adjustment for several covariates known to influence both risk of embolism and propensity for antiplatelet use, the adjusted odds ratio for a symptomatic embolic event was 0.36 (95% confidence interval, 0.19-0.68; P=.002) for patients receiving continuous daily antiplatelet therapy.nnnCONCLUSIONSnThe risk of symptomatic emboli associated with IE was reduced in patients who received continuous daily antiplatelet therapy before onset of IE.

Correlation of Histopathologic Findings with Clinical Outcome in Necrotizing Fasciitis

BACKGROUNDnNecrotizing fasciitis is an uncommon disease with high morbidity and mortality rates. Little is known about the role of histopathologic examination in disease prognosis.nnnMETHODSnA retrospective study was conducted to determine what correlations, if any, exist between the histopathologic features of resected tissue in patients with necrotizing fasciitis and clinical outcome.nnnRESULTSnEighty-two cases of necrotizing fasciitis that occurred between January 1990 and December 2002 were identified. Histopathologic findings were available for review in 63 cases. A novel histopathologic classification scheme, based on hematoxylin-eosin and Gram stain results, was developed. The classification scheme included 3 stages: stage I, characterized by an intense neutrophilic response and an absence of bacteria in infected tissue; stage II, characterized by the presence of a moderate-to-severe neutrophilic response and positive Gram stain results or by minimal to absent neutrophilic response with a negative Gram stain result; and stage III, characterized by the presence of few or no polymorphonuclear leukocytes and a Gram stain result positive for bacteria during histopathologic examination. Patients with stage I findings had a significantly lower risk of death than patients with stage III findings (7.1% vs. 47%; odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01-0.8; P=.03). Patients with stage II findings had a significantly lower mortality rate than patients with stage III findings (14.2% vs. 47%; OR, 0.2; 95% CI, 0.04-0.9; P=.04). Due to the small number of deaths (n=11) in patients for whom histopathologic examination of resected tissue was performed, multivariate analysis was not done.nnnCONCLUSIONSnResults of this study suggest that histopathologic findings may correlate with clinical outcome in cases of necrotizing fasciitis. Because the histopathologic scheme is based on results of commonly available stains, it could be easily adopted for use in other institutions that could further evaluate its usefulness as a prognostic tool.

Quality and Strength of Evidence of the Infectious Diseases Society of America Clinical Practice Guidelines

OBJECTIVEnTo describe the distribution and temporal trends of the quality and strength of evidence supporting recommendations in the Infectious Diseases Society of America (IDSA) clinical practice guidelines.nnnMETHODSnGuidelines either issued or endorsed by IDSA from March 1994 to July 2009 were evaluated using the IDSA-US Public Health Service Grading System. In this system, the letters A-E signify the strength of the recommendation, and numerals I-III indicate the quality of evidence supporting these recommendations. The distribution of the guideline recommendations among strength of recommendation and quality of evidence classes was quantified. Temporal changes between the first and current guideline version were evaluated.nnnRESULTSnApproximately one-half (median, 50.0%; interquartile range [IQR], 38.1%-58.6%) of the recommendations in the current guidelines are supported by level III evidence (derived from expert opinion). Evidence from observational studies (level II) supports 31% of recommendations (median, 30.9%; IQR, 23.3%-43.2%), whereas evidence based on ≥ 1 randomized clinical trial (level I) constitutes 16% of the recommendations (median, 15.8%; IQR, 5.8%-28.3%). The strength of recommendation was mainly distributed among classes A (median, 41.5%; IQR, 28.7%-55.6%) and B (median, 40.3%; IQR, 27.1%-47.9%). Among guidelines with ≥ 1 revised version, the recommendations moved proportionately toward more level I evidence (+12.4%). Consequently, there was a proportional increase in class A recommendations (+11.1%) with a decrease in class C recommendations (-23.5%).nnnCONCLUSIONSnThe IDSA guideline recommendations are primarily based on low-quality evidence derived from nonrandomized studies or expert opinion. These findings highlight the limitations of current clinical infectious diseases research that can provide high-quality evidence. There is an urgent need to support high-quality research to strengthen the evidence available for the formulation of guidelines.

Pacemaker infection due to Mycobacterium fortuitum

Pacemaker infection with Mycobacterium fortuitum has not been reported previously. We describe a case of pacemaker generator pocket infection and intravascular lead endocarditis due to Mycobacterium fortuitum. The entire pacing system was removed and the patient was treated successfully with a multidrug regimen for a total of 6 months.

Decreases in Case-Fatality and Mortality Rates for Invasive Pneumococcal Disease in Olmsted County, Minnesota, during 1995–2007: A Population-Based Study

BACKGROUNDnFollowing the introduction of a 7-valent pneumococcal conjugate vaccine for children in 2000, there has been a decrease in the incidence of invasive pneumococcal disease among both children and adults in the United States. We evaluated the hypothesis that the case-fatality and mortality rates for invasive pneumococcal disease have also decreased since 2000.nnnMETHODSnWe conducted a population-based outcome study in Olmsted County, Minnesota, during the period 1995-2007 that involved patients of all ages.nnnRESULTSnFrom 1 January 1995 through 31 December 2007, a total of 180 eligible cases of invasive pneumococcal disease were identified in Olmsted County. During the 13-year study period, the overall case-fatality rate for invasive pneumococcal disease decreased from 19% (14 of 74 cases) in 1995-1999 to 5% (5 of 91 cases) in 2001-2007, an 83% decrease, after adjustment for age, sex, and Charlson comorbidity index score (P =.003). The largest decreases in case-fatality rate were seen among adults aged >/=65 years (an 86% decrease, from 31% [9 of 29 cases] to 8% [3 of 40 cases]; P=.02) and patients with invasive pneumonia (a 78% decrease, from 22% [12 of 55 cases] to 7% [5 of 72 cases]; P=.01). The overall mortality rate for invasive pneumococcal disease decreased from 2.9 deaths per 100,000 person-years in 1995-1999 to 0.7 deaths per 100,000 person-years in 2001-2007, a 78% decrease, after adjustment for age and sex in a Poisson regression model (P=.002).nnnCONCLUSIONSnSignificant decreases in the case-fatality and mortality rates for invasive pneumococcal disease were demonstrated in the population of Olmsted County. Additional studies are needed to confirm our findings in other populations.

Enterococcus avium endocarditis

We describe a rare case of Enterococcus avium endocarditis in a patient with an ovarian malignancy, and review 2 previously reported cases. We contend that Enterococcus avium bacteremia and endocarditis may be associated with gastrointestinal pathology.