Mycobacterium chimaera Outbreak Management and Outcomes at a Large Pediatric Cardiac Surgery Center.

BACKGROUND: In 2012, a global outbreak of invasive Mycobacterium chimaera (M. chimaera) infection was identified in patients after cardiopulmonary bypass surgery. Investigations revealed the source to be heater-cooler unit (HCU) exhaust, with point-source contamination discovered at the LivaNova HCU manufacturing plant (London, UK). We report our experience with affected HCUs at a high-volume pediatric cardiac surgery center in the United States. METHODS: A multidisciplinary task force was established for outbreak management, including removing contaminated HCUs from service. Patients identified as exposed to affected HCUs were systematically contacted. A call center was created for patient/family inquiries, and symptomatic patients were assessed using an institutional triage protocol, including laboratory/culture data and infectious diseases consultation. RESULTS: Cardiopulmonary bypass surgeries were performed in 4276 patients (median age: 2.1 years; range: 0-48.4 years) between October 2010 and October 2016. Call center volume was highest in the first 6 weeks after patient notification, totaling 307 calls and yielding 70 clinical patient assessments. Presenting symptoms included fatigue (60%), fever (49%), night sweats (46%), myalgias (34%), and weight loss (24%). Among the 70 assessed patients, echocardiogram (n = 30), cardiac computed tomography (n = 2), cardiac magnetic resonance imaging (n = 1), and pulmonary computed tomography (n = 1) did not reveal abnormalities suggestive of active infection. Infectious diseases consultation occurred in 23 (33%) patients. Acid-fast bacilli blood cultures were obtained in 30 patients; all were negative. CONCLUSIONS: Through a highly coordinated outreach effort, no patients have been found to have M. chimaera infection in the 6 years after exposure to contaminated HCUs. Ongoing vigilance for cases that may yet manifest is needed.

Does Clarithromycin Cause Hearing Loss? A 12-Year Review of Clarithromycin Therapy for Nontuberculous Mycobacterial Lymphadenitis in Children.

OBJECTIVE(S): The objective was to describe the characteristics of hearing losses documented in patients treated with clarithromycin alone for nontuberculous mycobacterial NTM lymphadenitis in a pediatric tertiary care center over a 12-year period. METHODS: An institutional review board (IRB) approval was obtained. A database search was performed using the ICD-10 diagnosis codes 31.0, 31.1, and 31.8 between January 2004 and January 2017. A REDCap database was created to record variables. Patients were included if they received clarithromycin alone and had, at the minimum, a baseline audiology assessment, and 1 further evaluation during treatment. Fisher's exact test was used to analyze categorical variables, and Wilcoxon rank sum test was used to analyze continuous variables. RESULTS: A total of 167 patients with cervicofacial NTM were identified. Of them, 42 patients fulfilled inclusion criteria. Three children (7%) developed a hearing loss (HL) between 25 and 63 days after starting treatment. HL was unilateral in 2 children. HL persisted in 1 child following cessation of treatment. However, this patient had Rubinstein Taybi syndrome, limiting our ability to attribute the HL solely to clarithromycin. CONCLUSION: We noted a 7% hearing loss rate in our series. Confounding issues, such as 1 patient with a syndrome potentially contributing to HL, and limitations to this study, including retrospective design and loss to follow-up, temper our ability to conclude that clarithromycin was the sole cause of these HL. However, enough supporting data for a role in clarithromycin causing HL exist that testing should be considered for patients undergoing long-term clarithromycin treatment.

Safety of Outpatient Parenteral Antimicrobial Therapy in Children.

BACKGROUND AND OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) provides numerous benefits but may pose unique risks in children. We aimed to determine rates of OPAT antimicrobial- and intravenous access-related complications and their associations with specific antimicrobials and type of intravenous access in pediatric patients. METHODS: Observational cohort study of patients receiving OPAT from August 2008 to May 2015 cared for by the Infectious Diseases service at a tertiary children's hospital. Primary outcome was antimicrobial discontinuation (AD) because of OPAT-associated complications. Secondary outcomes were unplanned outpatient healthcare visits and readmissions from OPAT-associated complications. RESULTS: Seven hundred and seven intravenous antimicrobials were prescribed in 540 cases. Nondevice-associated musculoskeletal infection was the most common diagnosis (39%). Ceftriaxone (30%), cefazolin (27%) and vancomycin (22%) were the most commonly used antimicrobials. Complications led to AD, ≥1 unplanned outpatient healthcare visit and ≥1 readmission in 23%, 30% and 17% of cases, respectively. Compared with use of ceftriaxone, use of oxacillin was associated with a significantly higher risk of AD because of any antimicrobial-related complication [hazard ratio (HR), 3.3; 95% confidence interval (CI): 1.2-9.7) and because of hepatic transaminitis (HR, 32.8; 95% CI: 4.02-268.2). Subjects treated with intravenous clindamycin (HR, 2.6; 95% CI: 1.1-5.8) and with a peripherally inserted central catheter (HR, 2.6; 95% CI: 1.04-6.3) were more likely to have unplanned outpatient visits. CONCLUSIONS: Use of oxacillin during OPAT was associated with higher rate of AD. Patients treated with clindamycin and those with a peripherally inserted central catheter had higher rates of unplanned outpatient visits. Providers should strongly consider alternative treatment options when possible.

The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy.

RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 1993-2006 for transplant recipients, and 2000-2005 for patients with cancer. RSV was the most common respiratory virus identified. There were 17 (10% of all patients) deaths overall, of which 12 were at least partly attributed to the presence of a RVI. In multivariate models, LRT symptoms in the absence of upper respiratory symptoms on presentation (OR 10.2 [2.3, 45.7], p = 0.002) and adenoviral infection (OR 3.7 [1.1, 12.6], p = 0.034) were significantly associated with poor outcome, defined as death or disability related to RVI. All of the deaths occurred in patients who had received either solid organ or HSCT. There were no infections resulting in death or disability in the cancer chemotherapy group.

Group B Streptococcus bacteremia elicits beta C protein-specific IgMand IgG in humans.

Group B Streptococcus (GBS) beta C protein elicits protective antibodies in experimental animals, making beta C protein an attractive component of a human GBS glycoconjugate vaccine. We determined whether natural exposure to beta C protein elicits antibodies in humans. Geometric mean concentrations (in micrograms per milliliter) of beta C-specific immunoglobulin (Ig) M and IgG as determined by enzyme-linked immunosorbent assay were similar in serum from 16 colonized (0.82 and 0.76, respectively) and 48 age-matched noncolonized (0.96 and 0.74, respectively) pregnant women. Serum from 3 women with beta C GBS bacteremia had significantly higher levels of IgM (6.0) and IgG (52.9) (P=.01 and 0.01, respectively). Invasive disease but not colonization elicits beta C-specific IgM and IgG.

Quantitative determination of immunoglobulin G specific for group B streptococcal beta C protein in human maternal serum.

The beta C protein of group B streptococci (GBS) elicits antibody that is protective against GBS challenge in animals and is considered to be a potential component of a GBS conjugate vaccine. We developed a quantitative enzyme-linked immunosorbent assay to measure beta-specific serum immunoglobulin G (IgG) levels and used it to compare beta-specific IgG in a group of mothers of neonates with invasive type Ib/beta GBS disease and a group of mothers colonized with Ib/beta strains whose neonates remained well. beta-Specific IgG concentrations from these 2 groups were similar. To investigate differences in beta-specific antibody in animals and humans, protein fragments were generated that corresponded to major regions within the beta C protein. A single major region was predominantly recognized in human and rabbit serum samples. Thus, in contrast to immunized animals, no relationship was seen between levels of naturally acquired human beta-specific IgG and protection from neonatal disease. This difference was not explained by a major difference in epitope specificity.