Jorge P. Parada

Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy

Zygomycosis is increasingly reported as a cause of life-threatening fungal infections. A higher proportion of cases reported over the last decades have been in cancer patients, with or without hematopoietic stem cell transplantation (HSCT). The new anti-fungal agent voriconazole is a recently identified risk factor for developing zygomycosis. We reviewed the clinical characteristics and outcomes of a large cohort of cancer patients who developed zygomycosis after exposure to voriconazole. Health care professionals at 13 large cancer centers provided clinical information on cancer patients with zygomycosis and prior exposure to voriconazole. Criteria for inclusion were 5 days or more of voriconazole use and diagnostic confirmation with tissue or histology. Fifty-eight cases were identified among patients with hematologic malignancies, 62% including patients who underwent a HSCT procedure. Fifty-six patients received voriconazole for primary or secondary prophylaxis against fungal infection. In addition to prior exposure to voriconazole, patients also had several of the previously established risk factors for zygomycosis. Amphotericin B was the most commonly prescribed anti-fungal therapy. Overall mortality was 73%. We conclude that zygomycosis after exposure to voriconazole is a recently described entity that is frequently fatal, despite treatment with currently available anti-fungal agents and surgery.

Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands

BACKGROUND Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.

Corynebacterium endocarditis species-specific risk factors and outcomes

BackgroundCorynebacterium species are recognized as uncommon agents of endocarditis, but little is known regarding species-specific risk factors and outcomes in Corynebacterium endocarditis.MethodsCase report and Medline search of English language journals for cases of Corynebacterium endocarditis. Inclusion criteria required that cases be identified as endocarditis, having persistent Corynebacterium bacteremia, murmurs described by the authors as identifying the affected valve, or vegetations found by echocardiography or in surgical or autopsy specimens. Cases also required patient-specific information on risk factors and outcomes (age, gender, prior prosthetic valve, other prior nosocomial risk factors (infected valve, involvement of native versus prosthetic valve, need for valve replacement, and death) to be included in the analysis. Publications of Corynebacterium endocarditis which reported aggregate data were excluded. Univariate analysis was conducted with chi-square and t-tests, as appropriate, with p = 0.05 considered significant.Results129 cases of Corynebacterium endocarditis involving nine species met inclusion criteria. Corynebacterium endocarditis typically infects the left heart of adult males and nearly one third of patients have underlying valvular disease. One quarter of patients required valve replacement and one half of patients died. Toxigenic C. diphtheriae is associated with pediatric infections (p < 0.001). Only C. amycolatum has a predilection for women (p = 0.024), while C. pseudodiphtheriticum infections are most frequent in men (p = 0.023). C. striatum, C. jeikeium and C. hemolyticum are associated with nosocomial risk factors (p < 0.001, 0.028, and 0.024, respectively). No species was found to have a predilection for any particular heart valve. C. pseudodiphtheriticum is associated with a previous prosthetic valve replacement (p = 0.004). C. jeikeium infections are more likely to require valve replacement (p = 0.026). Infections involving toxigenic C. diphtheriae and C. pseudodiphtheriticum are associated with decreased survival (p = 0.001 and 0.032, respectively).ConclusionWe report the first analysis of species-specific risk factors and outcomes in Corynebacterium endocarditis. In addition to species-specific associations with age, gender, prior valvular diseases, and other nosocomial risk factors, we found differences in rates of need for valve replacement and death. This review highlights the seriousness of these infections, as up to 28% of patients required valve replacement and 43.5% died.

Onset of symptoms and time to diagnosis of Clostridium difficile-associated disease following discharge from an acute care hospital.

OBJECTIVE To identify patients with a diagnosis of Clostridium difficile-associated disease (CDAD) in the ambulatory care setting and determine the relationship of symptom onset and diagnosis to prior hospitalization and exposure to antimicrobials. DESIGN Single-center, retrospective study. METHODS Medical records were reviewed for outpatients and hospitalized patients with a stool assay positive for C. difficile toxin A from January 1998 through March 2005. Patients with recurrent CDAD or residing in an extended-care facility were excluded. CDAD in patients who had been hospitalized in the 100 days prior to diagnosis was considered potentially hospital-associated. RESULTS Of the 84 patients who met the inclusion criteria, 75 (89%) received a diagnosis 1-60 days after hospital discharge (median, 12 days), and 71 (85%) received a diagnosis within 30 days after discharge. Of the 69 patients whose records contained information regarding time of symptom onset, 62 (90%) developed diarrhea within 30 days of a previous hospital discharge, including 7 patients with symptom onset prior to discharge and 9 with onset on the day of discharge. The median time from symptom onset to diagnosis was 6 days. Of 84 patients, 77 (92%) had received antimicrobials during a prior hospitalization, but 55 (65%) received antimicrobials both as inpatients and as outpatients. CONCLUSION If all cases of CDAD diagnosed within 100 days of hospital discharge were assumed to be hospital-associated, 71 (85%) of 84 patients with CDAD were identified within 30 days, and 75 (89%) of 84 were identified by day 60. Continued outpatient antimicrobial exposure confounds determination of whether late-onset cases are community- or hospital-associated.

Epidemiology of hospital-acquired infections in veterans with spinal cord injury and disorder.

OBJECTIVE To describe the epidemiology of hospital-acquired infections (HAIs) in veterans with spinal cord injury and disorder (SCI&D). DESIGN Retrospective medical record review. SETTING Midwestern Department of Veterans Affairs spinal cord injury center. PARTICIPANTS A total of 226 patients with SCI&D hospitalized at least once during a 2-year period (October 1, 2001, through September 30, 2003). RESULTS A total of 549 hospitalizations were included in the analysis (mean duration of hospitalization, 33.7 days); an HAI occurred during 182 (33.2%) of these hospitalizations. A total of 657 HAIs occurred during 18,517 patient-days in the hospital (incidence rate, 35.5 HAIs per 1,000 patient-days). Almost half of the 226 patients had at least 1 HAI; the mean number of HAIs among these patients was 6.0 HAIs per patient. The most common HAIs were urinary tract infection (164 [25.0%] of the 657 HAIs; incidence rate, 8.9 cases per 1,000 patient-days), bloodstream infection (111 [16.9%]; incidence rate, 6.0 cases per 1,000 patient-days), and bone and joint infection (103 [15.7%]; incidence rate, 5.6 cases per 1,000 patient-days). The most common culture isolates were gram-positive bacteria (1,082 [45.6%] of 2,307 isolates), including Staphylococcus aureus, and gram-negative bacteria (1,033 [43.6%] of isolates), including Pseudomonas aeruginosa. Multivariable regression demonstrated that predictors of HAI were longer length of hospital stay (P=.002), community-acquired infection (P=.007), and use of a urinary invasive device (P=.01) or respiratory invasive device (P=.04). CONCLUSIONS The overall incidence of HAIs in persons with SCI&D was higher than that reported for other populations, confirming the increased risk of HAI in persons with spinal cord injury. The increased risk associated with longer length of stay and with community-acquired infection suggests that strategies are needed to reduce the duration of hospitalization and to effectively treat community-acquired infection, to decrease infection rates. There is significant room for improvement in reducing the incidence of HAIs in this population.

Hepatotoxicity associated with long- versus short-course HIV-prophylactic nevirapine use: A systematic review and meta-analysis from the Research on Adverse Drug events And Reports (RADAR) project

Background and objective: The antiretroviral nevirapine can cause severe hepatotoxicity when used ‘off-label’ for preventing mother-to-child HIV transmission (PMTCT), newborn post-exposure prophylaxis and for pre- and post-exposure prophylaxis among non-HIV-infected individuals. We describe the incidence of hepatotoxicity with short-versus long-course nevirapine-containing regimens in these groups.Methods: We reviewed hepatotoxicity cases among non-HIV-infected individuals and HIV-infected pregnant women and their offspring receiving short- (≤4 days) versus long-course (≥5 days) nevirapine prophylaxis. Sources included adverse event reports from pharmaceutical manufacturers and the US FDA, reports from peer-reviewed journals/scientific meetings and the Research on Adverse Drug events And Reports (RADAR) project. Hepatotoxicity was scored using the AIDS Clinical Trial Group criteria.Results: Toxicity data for 8216 patients treated with nevirapine-containing regimens were reviewed. Among 402 non-HIV-infected individuals receiving short- (n = 251) or long-course (n = 151) nevirapine, rates of grade 1–2 hepatotoxicity were 1.99% versus 5.30%, respectively, and rates of grade 3–4 hepatotoxicity were 0.00% versus 13.25%, respectively (p < 0.001 for both comparisons). Among 4740 HIV-infected pregnant women receiving short- (n = 3031) versus long-course (n=1709) nevirapine, rates of grade 1–2 hepatotoxicity were 0.62% and 7.04%, respectively, and rates of grade 3–4 hepatotoxicity were 0.23% versus 4.39%, respectively (p< 0.001 for both comparisons). The rates of grade 3–4 hepatotoxicity among 3074 neonates of nevirapine-exposed HIV-infected pregnant women were 0.8% for those receiving short-course (n = 2801) versus 1.1 % for those receiving long-course (n=273) therapy (p < 0.72).Conclusions: Therapy duration appears to significantly predict nevirapine hepatotoxicity. Short-course nevirapine for HIV prophylaxis is associated with fewer hepatotoxic reactions for non-HIV-infected individuals or pregnant HIV-infected women and their offspring, but administration of prophylactic nevirapine for ≥2 weeks appears to be associated with high rates of hepatotoxicity among non-HIV-infected individuals and HIV-infected pregnant mothers. When full highly active antiretroviral therapy (HAART) regimens are not available, single-dose nevirapine plus short-course nucleoside reverse transcriptase inhibitors to decrease the development of HIV viral resistance is an essential therapeutic option for PMTCT and these data support the safety of single-dose nevirapine in this setting.

Intrathecal Colistin and Sterilization of Resistant Pseudomonas Aeruginosa Shunt Infection

OBJECTIVE: To report 2 cases of multidrug-resistant (MDR) Pseudomonas aeruginosa meningitis and ventriculo-peritoneal shunt (VPS) infection successfully sterilized with intrathecal colistin 10 mg/day after development of nephrotoxicity associated with intravenous administration. CASE SUMMARIES: Case 1. A 69-year-old African American woman with a history of subarachnoid hemorrhage and hydrocephalus requiring VPS placement was admitted with VPS infection and meningitis. Cerebrospinal fluid (CSF) cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but rapidly discontinued due to development of renal dysfunction. Intravenous colistin was the probable cause of the adverse effect. Intrathecal colistin was initiated via an externalized VPS, with subsequent improvement in white blood cell counts in the CSF. Follow-up CSF cultures remained sterile and renal function returned to baseline. Case 2. A 69-year-old white woman with a history of subarachnoid hemorrhage, hydrocephalus, and VPS was transferred from an extended-care facility for management of a VPS infection. CSF cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but subsequently discontinued due to worsening renal function that, as with the first case, probably correlated with colistin administration and persisted despite dose adjustment. Therapy was changed to intrathecal administration, with subsequent normalization of her CSF white blood cell counts and sterilization of cultures. DISCUSSION: The limited availability of antibiotics for treatment of highly resistant or MDR gram-negative organisms has prompted clinicians to reconsider the use of older drugs. Prior reports have suggested that intravenous colistin is a potential alternative for treating highly resistant gram-negative central nervous system infections, specifically Acinetobacter, but its use is limited by nephrotoxicity. Our experience suggests that intrathecal colistin is a potentially curative intervention for the treatment of severe MDR P. aeruginosa meningitis and VPS infections in patients in whom intravenous colistin is not an option. CONCLUSIONS: Intrathecal use of colistin is a potentially safe, effective, and viable treatment option for MDR P. aeruginosa central nervous system infections when intravenous administration is not feasible.

Systematic review of piperacillin-induced neutropenia.

Because penicillin agents are implicated in granulopoiesis inhibition, healthcare professionals frequently consider discontinuation of such therapy in patients with decreasing white blood cell counts. No systematic review to date has described piperacillin and the patient population at risk for this adverse drug reaction (ADR).This review sought to assess the occurrence of piperacillin-induced neutropenia, describe characteristics of affected patients and assess the reporting modalities that most accurately classify this ADR. Case reports, cohort studies and clinical trials identified by comprehensive searches of PubMed and the US FDA Adverse Event Reporting System (AERS) database were reviewed for patient demographics, duration and dose of piperacillin or piperacillin-tazobactam treatment and the occurrence of neutropenia. Causality assessments were performed.Six published case reports, three cohort studies, 178 clinical trials and two compilations of phase I–III trials were reviewed. Review of case reports was notable in that the duration of β-lactam therapy prior to the noting of leukopenia always exceeded 15 days. No deaths were recorded in this group. Among 13 816 patients enrolled in non-neutropenic fever studies, the occurrence of piperacillin-induced neutropenia was rare: five patients (0.04%) developed neutropenia; none died. The demographics for this group were poorly documented. Through the AERS database, we identified 366 unique cases of piperacillin or piperacillin-tazobactam-induced haematological abnormalities, including neutropenia (n = 183, 50.0%), leukopenia, (n = 99, 27%), agranulocytosis (n = 58, 15.8%) and others. In 62 cases, patients received between 1 and 14 days of therapy (mean 7.7 + 4.1 days). Overall, there were 82 (22.4%) deaths.Reports of haematological ADRs among patients receiving piperacillin or piperacillin-tazobactam are rare. Report of neutropenia associated with piperacillin usage prior to 15 days of therapy is a novel finding that requires further evaluation. Current reporting methods poorly characterise patient groups at risk.

Clinical Syndromes Associated with Adult Pneumococcal Cellulitis

Streptococcus pneumoniae is an uncommonly recognized etiology of cellulitis in adults. A review of the literature uncovered 30 cases of pneumococcal skin infection in adults. Typically, all patients with pneumococcal cellulitis had an underlying chronic illness, or were immunocompromised by drug or alcohol abuse. Pneumococcal cellulitis presents as two distinctive clinical syndromes: one with extremity involvement in individuals with diabetes and substance abuse; and a second involving the head, neck and upper torso in individuals with systemic lupus erythematosis, nephrotic syndrome and hematologic disorders. For each there are statistically significant associations between the location of pneumococcal cellulitis and underlying clinical disorders. In contrast to other common bacterial etiologies, pneumococcal cellulitis is frequently associated with blood stream invasion, tissue necrosis and suppurative complications. Patients often require surgical interventions and prolonged hospitalizations. A high degree of suspicion and early aggressive management is needed for those presenting with cellulitis characterized by bullae and violaceous color.Streptococcus pneumoniae is an uncommonly recognized etiology of cellulitis in adults. A review of the literature uncovered 30 cases of pneumococcal skin infection in adults. Typically, all patients with pneumococcal cellulitis had an underlying chronic illness, or were immunocompromised by drug or alcohol abuse. Pneumococcal cellulitis presents as two distinctive clinical syndromes: one with extremity involvement in individuals with diabetes and substance abuse; and a second involving the head, neck and upper torso in individuals with systemic lupus erythematosis, nephrotic syndrome and hematologic disorders. For each there are statistically significant associations between the location of pneumococcal cellulitis and underlying clinical disorders. In contrast to other common bacterial etiologies, pneumococcal cellulitis is frequently associated with blood stream invasion, tissue necrosis and supporative complications. Patients often require surgical interventions and prolonged hospitalizations. A high degree of suspicion and early aggressive management is needed for those presenting with cellulitis characterized by bullae and violaceous color.

Granulomatous hepatitis due to Bartonella henselae infection in an immunocompetent patient.

BackgroundBartonella henselae (B. henselae) is considered a rare cause of granulomatous hepatitis. Due to the fastidious growth characteristics of the bacteria, the limited sensitivity of histopathological stains, and the non-specific histological findings on liver biopsy, the diagnosis of hepatic bartonellosis can be difficult to establish. Furthermore, the optimal treatment of established hepatic bartonellosis remains controversial.Case presentationWe present a case of hepatic bartonellosis in an immunocompetent woman who presented with right upper quadrant pain and a five cm right hepatic lobe mass on CT scan. The patient underwent a right hepatic lobectomy. Surgical pathology revealed florid necrotizing granulomatous hepatitis, favoring an infectious etiology. Despite extensive histological and serological evaluation a definitive diagnosis was not established initially. Thirteen months after initial presentation, hepatic bartonellosis was diagnosed by PCR studies from surgically excised liver tissue. Interestingly, the hepatic granulomas persisted and Bartonella henselae was isolated from the patients enriched blood culture after several courses of antibiotic therapy.ConclusionThe diagnosis of hepatic bartonellosis is exceedingly difficult to establish and requires a high degree of clinical suspicion. Recently developed, PCR-based approaches may be required in select patients to make the diagnosis. The optimal antimicrobial therapy for hepatic bartonellosis has not been established, and close follow-up is needed to ensure successful eradication of the infection.