Steven J. Lawrence

Chronic Active Hepatitis B Exacerbations in Human Immunodeficiency Virus-Infected Patients Following Development of Resistance to or Withdrawal of Lamivudine

Lamivudine is a nucleoside analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Patients coinfected with HIV and HBV may have hepatitis flares when lamivudine therapy is discontinued or when resistance of HBV to lamivudine emerges. This retrospective, descriptive study conducted in three tertiary care medical centers describes patients coinfected with HIV type 1 and HBV who presented with a spectrum of clinical and subclinical hepatitic responses to lamivudine withdrawal or resistance. One patient had fulminant hepatic failure and a second patient had subclinical hepatitis when lamivudine therapy was discontinued and a more efficacious antiretroviral regimen was substituted. Three patients had flares of hepatitis after 13 to 18 months of lamivudine therapy. Lamivudine withdrawal or emergence of lamivudine-resistant mutants in patients coinfected with HIV and HBV may result in severe hepatitis. Clinicians caring for patients with coinfection with HIV and HBV should be aware of the possibility that a hepatitis B flare may occur in previously asymptomatic carrier patients.

Surveillance for vancomycin-resistant enterococci: Type, rates, costs, and implications

OBJECTIVE To evaluate 2 active surveillance strategies for detection of enteric vancomycin-resistant enterococci (VRE) in an intensive care unit (ICU). DESIGN Thirty-month prospective observational study. SETTING ICU at a university-affiliated referral center. PATIENTS All patients with an ICU stay of 24 hours or more were eligible for the study. INTERVENTION Clinical active surveillance (CAS), involving culture of a rectal swab specimen for detection of VRE, was performed on admission, weekly while the patient was in the ICU, and at discharge. Laboratory-based active surveillance (LAS), involving culture of a stool specimen for detection of VRE, was performed on stool samples submitted for Clostridium difficile toxin detection. RESULTS Enteric colonization with VRE was detected in 309 (17%) of 1,872 patients. The CAS method initially detected 280 (91%) of the 309 patients colonized with VRE, compared with 25 patients (8%) detected by LAS; colonization in 4 patients (1%) was initially detected by analysis of other clinical specimens. Most patients with colonization (76%) would have gone undetected by LAS alone, whereas use of the CAS method exclusively would have missed only 3 patients (1%) who were colonized. CAS cost Dollars 1,913 per month, or Dollars 57,395 for the 30-month study period. Cost savings of CAS from preventing cases of VRE colonization and bacteremia were estimated to range from Dollars 56,258 to Dollars 303,334 per month. CONCLUSIONS A patient-based CAS strategy for detection of enteric colonization with VRE was superior to LAS. In this high-risk setting, CAS appeared to be the most efficient and cost-effective surveillance method. The modest costs of CAS were offset by the averted costs associated with the prevention of VRE colonization and bacteremia.

Precise Dissection of an Escherichia coli O157:H7 outbreak by Single Nucleotide Polymorphism Analysis

ABSTRACT The current pathogen-typing methods have suboptimal sensitivities and specificities. DNA sequencing offers an opportunity to type pathogens with greater degrees of discrimination using single nucleotide polymorphisms (SNPs) than with pulsed-field gel electrophoresis (PFGE) and other methodologies. In a recent cluster of Escherichia coli O157:H7 infections attributed to salad bar exposures and romaine lettuce, a subset of cases denied exposure to either source, although PFGE and multiple-locus variable-number tandem-repeat analysis (MLVA) suggested that all isolates had the same recent progenitor. Interrogation of a preselected set of 3,442,673 nucleotides in backbone open reading frames (ORFs) identified only 1 or 2 single nucleotide differences in 3 of 12 isolates from the cases who denied exposure. The backbone DNAs of 9 of 9 and 3 of 3 cases who reported or were unsure about exposure, respectively, were isogenic. Backbone ORF SNP set sequencing offers pathogen differentiation capabilities that exceed those of PFGE and MLVA.

Current practices for treatment of respiratory syncytial virus and other non-influenza respiratory viruses in high-risk patient populations: a survey of institutions in the Midwestern Respiratory Virus Collaborative.

The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non‐influenza respiratory viruses in Midwestern transplant centers.

Outbreak of Salmonella javiana infection at a children's hospital

OBJECTIVE To determine the source of an outbreak of Salmonella javiana infection. DESIGN Case-control study. PARTICIPANTS A total of 101 culture-confirmed cases and 540 epidemiologically linked cases were detected between May 26, 2003, and June 16, 2003, in hospital employees, patients, and visitors. Asymptomatic employees who had eaten in the hospital cafeteria between May 30 and June 4, 2003, and had had no gastroenteritis symptoms after May 1, 2003, were chosen as control subjects. SETTING A 235-bed academic tertiary care childrens hospital. RESULTS Isolates from 100 of 101 culture-confirmed cases had identical pulsed-field gel electrophoresis patterns. A foodhandler with symptoms of gastroenteritis was the presumed index subject. In multivariate analysis, case subjects were more likely than control subjects to have consumed items from the salad bar (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.3-12.1) and to have eaten in the cafeteria on May 28 (aOR, 9.4; 95% CI, 1.8-49.5), May 30 (aOR, 3.6; 95% CI, 1.0-12.7), and/or June 3 (aOR, 4.0; 95% CI, 1.4-11.3). CONCLUSIONS Foodhandlers who worked while they had symptoms of gastroenteritis likely contributed to the propagation of the outbreak. This large outbreak was rapidly controlled through the use of an incident command center.

High-throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient

A 40‐year‐old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide‐based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities.

Epidemiology of infections following haploidentical peripheral blood hematopoietic cell transplantation

The use of T‐cell replete haploidentical hematopoietic cell transplant (haplo‐HCT) has increased substantially since the introduction of post‐transplant cyclophosphamide (PTCy) regimens. Limited data exist concerning infectious complications of haplo‐HCT utilizing mobilized peripheral blood (PB) hematopoietic cells.

Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies

BACKGROUND Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZVIN) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZVIN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). METHODS This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZVIN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZVIN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. RESULTS ZVIN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion. Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZVIN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. CONCLUSIONS In adults with HM receiving anti-CD20 monoclonal antibodies, ZVIN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4. CLINICALTRIALS.GOV identifier: NCT01460719.

Smoking association with influenza infection in renal transplant recipients

We identified 22 cases of influenza infection among renal transplant recipients and matched them with 66 controls by influenza season to explore risk factors for influenza infection. Active cigarette smoking was associated with influenza infection in this population (adjusted odds ratio 13.1; 95% confidence interval 2.3–76; P = 0.004).

Preparing for and Responding to Bioterrorist Attacks

Components of disease management that are applicable to the development of services for bioterrorism preparedness and response include collaborative practice models, population identification processes, reporting/feedback loops, process and outcome measurements, patient self-management education, and evidence-based practice guidelines. This management system should be flexible and applicable to all possible diseases associated with bioterrorism, while including specific management recommendations for each disease.There are many gaps in the US’s ability to respond to a bioterrorist attack that can only be filled by collaborative research among disciplines involved with bioterrorism preparedness; namely, basic, clinical, and behavioral sciences, public health, and law. Laboratory scientists will need to develop new and improved diagnostic tests, treatments, and protective measures. Behavioral science will have to treat many victims, both the sick and the ‘worried well’. While some states have adequate laws in place to facilitate public health authorities’ efforts to isolate sick patients and quarantine those exposed, many states do not, and their laws will require modification. Public health agencies must develop and evaluate information technologies and decision support systems for the early detection of a bioterrorist attack, for the tracking of victims who will require prophylactic treatment, and to assist physicians with diagnosis and treatment. Public health and hospitals must also prepare for the treatment of large numbers of patients by increasing surge capacity. Finally, one of the most notable deficiencies in response to recent bioterrorism events has been the inability of public health to provide timely and accurate information. Effective communication is a fundamental element of all aspects of an effective response to emergencies. Before a bioterrorist attack, the nation’s preparedness efforts should be evaluated through tabletop and full-scale exercises that are preceded by extensive professional and community education.The US Army Medical Research Institute of Infectious Diseases has identified six primary agents that may be potentially used in bioterrorism: Bacillus anthracis, variola virus, Yersinia pestis, Francisella tularensis, botulinum toxin, and the hemorrhagic fever viruses. These six were identified on the basis of the following criteria: availability of the agent, ease of production, lethality, infectivity, and stability. Disease management requires an understanding of exposure mechanisms and dose response because the route of exposure and the dose will impact on the way a disease presents. In addition to disease management strategies for bioterrorism in general, this article briefly reviews specific diagnosis, treatment, and infection control recommendations for the six primary bioterrorism diseases agents.