Jesse T. Jacob

Viral infections associated with haemophagocytic syndrome

Haemophagocytic syndrome (HPS) or haemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by a dysfunction of cytotoxic T cells and NK cells. This T cell/NK cell dysregulation causes an aberrant cytokine release, resulting in proliferation/activation of histiocytes with subsequent haemophagocytosis. Histiocytic infiltration of the reticuloendothelial system results in hepatomegaly, splenomegaly, lymphadenopathy and pancytopenia ultimately leading to multiple organ dysfunctions. Common clinical features include high fevers despite broad spectrum antimicrobials, maculopapular rash, neurological symptoms, coagulopathy and abnormal liver function tests. Haemophagocytic syndrome can be either primary, i.e. due to an underlying genetic defect or secondary, associated with malignancies, autoimmune diseases (also called macrophage activation syndrome) or infections. Infectious triggers are most commonly due to viral infections mainly of the herpes group, with EBV being the most common cause. HPS can be fatal if untreated. Early recognition of the clinical presentation and laboratory abnormalities associated with HPS and prompt initiation of treatment can be life saving. HPS triggered by viral infections generally does not respond to specific antiviral therapy but may be treated with immunosuppressive/immunomodulatory agents and, in refractory cases, with bone marrow transplantation. Copyright

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013

IMPORTANCE Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. RESULTS Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. CONCLUSIONS AND RELEVANCE In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

Aspergillus endocarditis: a review of the literature.

We present a case of cardiac device-related Aspergillus endocarditis in a patient with a pacemaker and an allogeneic bone marrow transplant to segue into a review of the Aspergillus endocarditis literature. Aspergillus endocarditis should be suspected in patients with underlying immunosuppression, negative cultures, and a vegetation on echocardiography. Diagnosis ultimately requires confirmation by tissue histology and culture. The optimal treatment approach often requires aggressive surgical debridement in conjunction with prolonged antifungal therapy.

Male genital tuberculosis.

A 51-year-old man presented with painless left testicular swelling for 1 month, with fevers, chills, night sweats, weight loss, and increased difficulty voiding over 6 months. He underwent radical orchiectomy; surgical pathology revealed granulomas containing acid-fast bacilli in the testis and epididymis. Male genital tuberculosis was diagnosed using nucleic acid amplification on urine and confirmed by positive urine and sputum cultures for Mycobacterium tuberculosis. Genital disease is an unusual extrapulmonary manifestation of tuberculosis, often seen in middle-aged men with renal or pulmonary tuberculosis. Clinical findings are variable, but commonly include dysuria with sterile pyuria or a painless testicular mass. Initial diagnosis is often incidentally made on pathological specimens and confirmed with nucleic acid amplification and cultures. Treatment using a standard four-drug regimen is usually sufficient; surgery is rarely required. This case is used to raise awareness of, and formulate a minimally invasive diagnostic approach to, this unusual but important entity.

Acute forms of tuberculosis in adults.

Although typically considered a chronic disease, tuberculosis (TB) has protean acute manifestations, the major forms of which are reviewed in this article. The pathogenesis of acute TB, although still incompletely understood, may be related to both epidemiologic and genetic host factors. Miliary TB manifests as a nonspecific clinical syndrome with a high mortality rate. The most well-known form of acute TB is meningitis, characterized by fever, nuchal rigidity, and a lymphocytic pleocytosis of the cerebrospinal fluid. Acute abdominal TB may present with obstruction or less commonly as perforated viscus or peritonitis. Critically ill patients may have acute respiratory distress syndrome, shock, or disseminated intravascular coagulopathy. The spectrum of disease makes diagnosis of acute TB difficult unless clinical suspicion of disease is high, but the high mortality mandates its consideration. Early initiation of therapy is crucial to optimize clinical outcome.

Emerging trends in antibiotic use in US hospitals: quality, quantification and stewardship

Three major trends in antibiotic use in US hospitals have emerged over the last few years: antibiotics as quality metrics, persistent use of different measures of antibiotic consumption and the emergence of antibiotic stewardship programs. Compared with Europe, where approaches are heterogeneous but generally consistent, the USA currently lacks the infrastructure to monitor antibiotic resistance and antibiotic consumption locally. Both have implemented programmatic strategies for prudent antibiotic use. The USA appears to have implemented processes more systematically to measure the quality of antibiotic use.

Distribution of Pathogens in Central Line–Associated Bloodstream Infections among Patients with and without Neutropenia following Chemotherapy: Evidence for a Proposed Modification to the Current Surveillance Definition

OBJECTIVE Many bloodstream infections (BSIs) occurring in patients with febrile neutropenia following cytotoxic chemotherapy are due to translocation of intestinal microbiota. However, these infections meet the National Healthcare Safety Network (NHSN) definition of central line-associated BSIs (CLABSIs). We sought to determine the differences in the microbiology of NHSN-defined CLABSIs in patients with and without neutropenia and, using these data, to propose a modification of the CLABSI definition. DESIGN Retrospective review. SETTING Two large university hospitals over 18 months. METHODS All hospital-acquired BSIs occurring in patients with central venous catheters in place were classified using the NHSN CLABSI definition. Patients with postchemotherapy neutropenia (500 neutrophils/mm(3) or lower) at the time of blood culture were considered neutropenic. Pathogens overrepresented in the neutropenic group were identified to inform development of a modified CLABSI definition. RESULTS Organisms that were more commonly observed in the neutropenic group compared with the nonneutropenic group included Escherichia coli (22.7% vs 2.5%; P < .001) but not other Enterobacteriaceae, Enterococcus faecium (18.2% vs 6.1%; P = .002), and streptococci (18.2% vs 0%; P < .001). Application of a modified CLABSI definition (removing BSI with enterococci, streptococci, or E. coli) excluded 33 of 66 neutropenic CLABSIs and decreased the CLABSI rate in one study hospital with large transplant and oncology populations from 2.12 to 1.79 cases per 1,000 line-days. CONCLUSIONS Common gastrointestinal organisms were more common in the neutropenia group, suggesting that many BSIs meeting the NHSN criteria for CLABSI in the setting of neutropenia may represent translocation of gut organisms. These findings support modification of the NHSN CLABSI definition.

The stigmatization of leprosy in India and its impact on future approaches to elimination and control.

Traditionally, India holds the unenviable position of the origin of leprosy. The disease is thought to have then spread, via trade and war, to China, Egypt, and the Middle East, and later to Europe and the Americas. From antiquity to modernity, Indian society treated leprosy singularly with respect to custom and law, a response shaped by both scientific knowledge and cultural attitudes. Indias future challenges in leprosy control include multiple systems of medicine, stigma, and educational knowledge gaps. By looking through the historical window of leprosy in India, we propose that continued success in elimination and control requires a holistic approach addressing these issues (Image 1).

Severity of Human Rhinovirus Infection in Immunocompromised Adults Is Similar to That of 2009 H1N1 Influenza

ABSTRACT This retrospective chart review of patients at a tertiary referral center compares characteristics and clinical features of patients diagnosed with human rhinovirus (HRV) infection to those of patients with 2009 H1N1 influenza A (pH1N1) during the pandemic respiratory season of 2009 to 2010. Hospital admission rates, intensive care unit (ICU) admissions, and mortality were not statistically different between the HRV and pH1N1 groups; however, more patients in the HRV group were considered immunocompromised.

Transplantation and tropical infectious diseases

The number of transplant recipients with tropical infectious diseases is growing due to increasing international travel and the rising number of transplants taking place in the tropics and subtropics. With increases in population migration, the prevalence of individuals infected with geographically restricted organisms also rises. There are three potential categories of tropical infections in transplant patients: (1) donor-related infections transmitted by the graft or through transfusion of blood products; (2) reactivation or recrudescence of latent infections in the donor recipient; and (3) de novo acquisition of infection in the post-transplant period through the traditional route of infection. We present an overall discussion of the association of parasitic (protozoa and helminths) and non-parasitic (viral, bacterial, and fungal) tropical infectious diseases and solid-organ and hematopoietic transplantation. We also suggest potential screening guidelines for some of these tropical infections.