Nancy F. Crum

Comparisons of causes of death and mortality rates among HIV-infected persons : Analysis of the pre-, early, and late HAART (Highly active antiretroviral therapy) eras

Methods:Comparisons of death-related variables during the 3 eras were performed. Results:The number of deaths declined over the study period, with 987 deaths in the pre-HAART era, 159 deaths in the early HAART era (1997-1999), and 78 deaths in the late HAART era (2000-2003) (P < 0.01). The annual death rate peaked in 1995 (10.3 per 100 patients) and then declined to <2 deaths per 100 persons in the late HAART era (P < 0.01). The proportion of deaths attributable to infection decreased, but infection remained the leading cause of death in our cohort, followed by cancer. Of those who died, there was an increasing proportion of non-HIV-related deaths (32% vs. 9%; P < 0.01), including cardiac disease (22% vs. 8%; P < 0.01) and trauma (8% vs. 2%; P = 0.01) in the post-HAART versus pre-HAART era. Despite the absence of intravenous drug use and the low prevalence of hepatitis C coinfection in our cohort, an increasing proportion of deaths in the HAART era were attributable to liver disease, although the numbers are small. Conclusions:Despite increasing concerns regarding antiretroviral resistance, the death rate among HIV-infected persons in our cohort continues to decline. Our data show a lower death rate than that reported among many other US HIV-infected populations; this may be the result of open access to health care. A shift in the causes of death toward non-HIV-related causes suggests that a more comprehensive health care approach may be needed for optimal life expectancy; this may include enhanced screening for malignancy and heart disease as well as preventive measures for liver disease and accidents.

Pyogenic liver abscess with a focus on Klebsiella pneumoniae as a primary pathogen: an emerging disease with unique clinical characteristics.

OBJECTIVES:Pyogenic liver abscess is a common intraabdominal infection. Historically, Escherichia coli (E. coli) has been the predominant causative agent. Klebsiella liver abscess (KLA) was first reported in Taiwan and has surpassed E. coli as the number one isolate from patients with hepatic abscesses in that country and reports from other countries, including the United States, have increased. We examined the microbiologic trends of pyogenic liver abscess at our institution to determine if a similar shift in etiologic agents was occurring.METHODS:We examined all cases of liver abscess at our institution from 1999 to 2003 via a retrospective chart review of inpatient records and reviewed the English literature via a MEDLINE search for all U.S. cases of KLA.RESULTS:Since 1966, only 12 cases of KLA have been reported in the United States. We report six cases of KLA at our institution alone; 2 patients were not Asian, and 4 were not diabetic. Klebsiella pneumoniae (K. pneumoniae) was the most common cause of pyogenic hepatic abscess at our institution over the last 5-yr period. When comparing Klebsiella versus other causes of pyogenic liver abscess, there were no significant differences in demographics or laboratory findings; however, most of our Klebsiella cases occurred among Filipinos. Review of the 18 cases of K. pneumoniae liver abscess in the United States showed that Klebsiella cases occurred predominantly among middle-aged men; 83% had concurrent bacteremia and 28% had metastatic complications. An increasing number of cases were reported from the United States since the mid-1990s.CONCLUSIONS:These data suggest that KLA may represent an emerging disease in Western countries, such as the United States. The diagnosis of K. pneumoniae should be considered in all cases of liver abscess, and appropriate antibiotic therapy and a diagnostic work-up for metastatic complications should be employed.

Infections associated with tumor necrosis factor-α antagonists

Abstract: Tumor necrosis factor (TNF)-α antagonists are promising therapeutic agents for patients with severe autoimmune and rheumatologic conditions. Unfortunately, their use has been associated with an increased rate of tuberculosis, endemic mycoses, and intracellular bacterial infections. Infliximab, 1 of 3 available drugs in this novel class, appears to be associated with the greatest risk of infection, likely because of its long half-life and induction of monocyte apoptosis. Prospective trials are necessary to determine the exact risk associated with these agents, particularly the newer TNF-α antagonists. More specific TNF-α blockers, which reduce inflammation while maintaining adequate immunity, are needed. In the meantime, a thorough work-up is mandatory for all febrile illness occurring in TNF-α blocker recipients. We present 4 patients who developed severe infections during TNF-α antagonist therapy, review the literature, and discuss current guidelines for surveillance and prophylaxis. Abbreviations: AIDS = acquired immunodeficiency syndrome, FDA = United States Food and Drug Administration, HIV = human immunodeficiency virus, PPD = purified protein derivative, RA = rheumatoid arthritis, TB = tuberculosis, TH1 = T-helper type 1, TNF = tumor necrosis factor, WBC = white blood cell count.

Incidence and risk factors for the occurrence of non‐AIDS‐defining cancers among human immunodeficiency virus‐infected individuals

The objective of this study was to determine the rates and predictors of non‐AIDS‐defining cancers (NADCs) among a cohort of human immunodeficiency virus (HIV)‐infected individuals.

Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies.

Abstract: Coccidioidomycosis is a fungal disease with protean manifestations endemic to the Lower Sonoran Life Zone, which includes the hot deserts of the southwestern United States and areas of Mexico. Two hundred and twenty-three patients were found to have coccidioidomycosis at our institution from 1994-2002, the largest reported cohort of coccidioidomycosis patients since the 1950s. Of these patients, 58% presented with isolated pulmonary disease, 14% had high (>1:16) complement fixation titers without clear evidence of dissemination, 22% had definite disseminated disease, and 5% had unclassified disease. Enzyme immunoassay was a reliable diagnostic tool in those with symptomatic disease, but had a low specificity in those who were asymptomatic. Complement fixation titers of ≥1:16 were associated with dissemination to bone or skin but were not helpful in evaluating central nervous system disease. Thirteen percent of patients with high complement fixation titers (>1:16) without clear evidence of dissemination on presentation and 7% of those with isolated pulmonary disease eventually progressed to disseminated disease; 30% of Filipino patients with pulmonary disease progressed to disseminated disease. Nonwhite race was a predictor for dissemination; African American patients more often developed disseminated bony disease while Filipinos were more likely to develop cutaneous or central nervous system disease. Relapse of disseminated coccidioidomycosis occurred in 24% of patients; the risk was highest (71%) among those with central nervous system disease. Azole therapy was generally inferior to amphotericin B in disseminated disease. Predictors of permanent disability included African American or Filipino race, central nervous system disease, and bony disease. Abbreviations:, CF = complement fixation, CNS = central nervous system, CSF = cerebrospinal fluid, CT = computed tomography, EIA = enzyme immunoassay, LDH = lactate dehydrogenase, MRI = magnetic resonance imaging, OR = odds ratio, VP = ventriculo-peritoneal.

Risk Factors for Community-Associated Methicillin-Resistant Staphylococcus aureus Infections in an Outbreak of Disease among Military Trainees in San Diego, California, in 2002

ABSTRACT An outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections was observed in a population of U.S. military trainees in the summer of 2002. A questionnaire was developed and administered to 206 trainees, 22 of whom had MRSA infections. Factors associated with infection were described by multivariable logistic regression modeling and included having a roommate in training with a prior skin infection (odds ratio [OR] = 3.44) or having a family member or friend who worked in a health care setting (OR = 2.79). Previous antibiotic use, hospitalization, or health problems were not associated with MRSA infection. This outbreak of MRSA skin infections in an otherwise-healthy, well-defined, military population provided an opportunity to describe risk factors for CA-MRSA which may help focus prevention efforts in this and other communities.

The emergence of severe, community-acquired methicillin-resistant Staphylococcus aureus infections

The number of community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections is rapidly increasing. Most CA-MRSA infections are localized soft tissue infections; however, severe life-threatening infections have been occasionally described. This report serves to increase the awareness of severe CA-MRSA infections by presenting a fulminant CA-MRSA infection with sepsis, endocarditis, septic pulmonary emboli, and extensive soft tissue and bone destruction. A review of the literature revealed 14 cases of severe CA-MRSA infections with a median age of 13 y; 93% had no underlying medical condition. Only 1 case was initially treated with antibiotics effective for MRSA. The fatality rate was 64%, and 40% of patients who survived had significant disabilities.

Coccidioidomycosis Outbreak among United States Navy SEALs Training in a Coccidioides immitis–Endemic Area—Coalinga, California

An outbreak of coccidioidomycosis among 22 Navy SEALs occurred during training exercises in Coalinga, California. Ten (45%) of the 22 men had serologic evidence of acute coccidioidomycosis, the highest attack rate ever reported for a military unit. All case patients were symptomatic, and 50% had abnormal chest radiographs. There were no cases of dissemination and no deaths to date. Coccidioidomycosis continues to be a threat to military members and civilians who reside or train in areas where Coccidioides immitis, the causative agent, is endemic.

Halting a pneumococcal pneumonia outbreak among United States Marine Corps trainees

BACKGROUND Streptococcus pneumoniae is the leading cause of bacterial pneumonia in all age groups. Identifying outbreaks of pneumococcal disease and key risk factors may lead to improvements in vaccination and prevention strategies for high-risk groups. A significant outbreak of S. pneumoniae pneumonia that occurred among Marine recruits is reported here. METHODS An outbreak was investigated using standard microbiologic procedures and epidemiologic evaluation to define the extent of the outbreak, determine the microbiologic causative agent(s), identify risk factors for the development of disease, and institute preventive measures against further cases of pneumonia among recruits. RESULTS Fifty-two cases of radiographically confirmed pneumonia occurred among 3367 Marine recruits over a 2-week period in November 2000. Twenty-five of these cases occurred in a single company of 481 men, with an attack rate of 5.2%. Twelve of the 25 cases were caused by S. pneumoniae, serotypes 4 and 9v. The outbreak rapidly ended following isolation of cases, prophylaxis with oral azithromycin, and administration of the 23-valent pneumococcal vaccine. CONCLUSIONS This outbreak of pneumococcal disease occurred in the setting of intense military training and a crowded environment. The use of the pneumococcal vaccine year-round in military trainees and other high-risk populations to reduce pneumococcal disease should be considered.

An Outbreak of Conjunctivitis Due to a Novel Unencapsulated Streptococcus pneumoniae among Military Trainees

BACKGROUND Bacterial conjunctivitis usually occurs as sporadic cases; outbreaks are uncommon and usually are associated with school campuses. We report an outbreak of Streptococcus pneumoniae conjunctivitis at a military training facility. METHODS An outbreak investigation was done. Each case of conjunctivitis was evaluated with an assessment tool including demographic and clinical data. Conjunctival swabs were obtained. Pneumococci underwent standard testing, including serotyping with the Quellung reaction, capsular staining, and multilocus sequence typing. Sequence types were compared with previous reported outbreak strains by construction of dendrograms. Carriage rates of S. pneumoniae were determined among previously undiagnosed case patients with conjunctivitis, and a case-control study was performed. Control measures included education to increase hand washing, distribution of alcohol-based hand gel, and prompt treatment of patients with conjunctivitis. RESULTS During a 6-week period, 92 cases of conjunctivitis occurred among 3500 persons, with an attack rate of 1.75 cases per 100 person-months. Eighty cases (87%) were due to S. pneumoniae; 45 (49%) were confirmed, and 35 (38%) were probable. Ten percent of recruits surveyed carried the outbreak strain. Twenty-two percent self-reported symptoms consistent with conjunctivitis during the outbreak period; sharing washcloths was associated with conjunctivitis (odds ratio, 11.7; P=.03). The causative organism was resistant to azithromycin but susceptible to telithromycin. The outbreak strain was an unencapsulated S. pneumoniae that has not been previously described; it was most closely related to the sequence type causing the Dartmouth College (Hanover, NH) outbreak of conjunctivitis in 2002. CONCLUSIONS We report a conjunctivitis outbreak among military trainees caused by a novel, unencapsulated strain of S. pneumoniae.