[Show abstract][Hide abstract] ABSTRACT: Background: Hematopoietic Stem Cell Transplant recipients (HSCT) are at increased risk for severe infections, and empiric antibiotic choice may be driven anecdotally by single patient experiences in addition to local antibiograms. Knowledge of recent infection patterns may be insufficient to adjust prescribing practices. We report the results of a synchronized collaborative effort between Infectious Diseases and HSCT attendings to decrease meropenem (MERO) use on an HSCT unit.
Methods: Antibiotics prescription practice on HSCT unit before, during and after interventions.
Results: MERO use peaked at 392 days of therapy (DOT) per 1000 pt-days in October 2011 and remained greater than 300 DOT per 1000 patient days through 2012. Twice yearly reporting of microbiology data directly to the HSCT team identified an increasing incidence of candidemia in 2012. Interventions included data sharing of recently recovered pathogens, recommendations use MERO then de-escalate to piperacillin-tazobactam (PTZ) with negative cultures, daily huddles between ID and HSCT to de-escalate antibiotics when indicated, and visual display of MERO prescribing patterns in the HSCT unit. Over the following 8 months, MERO use declined to 72 DOT per 1000 pt-days after which ID/HSCT huddles were decreased in frequency to twice weekly (FIG1). MERO use has remained stable over the ensuing 6 months, averaging 100 DOT per 1000 pt-days. PTZ use increased modestly from 203 DOT per 1000 pt-days in October 2011 to a mean of 227 DOT per 1000 pt-days during the last 6 months. Overall usage of the two antibiotics in the HSCT unit remains lower (peak of 619 in October 2011 to 307 DOT per 1000 pt-days currently, FIG2).
Conclusion: Multi-prong intervention including education, data sharing, concentrated antibiotic prescribing practices and improved communication resulted in decreased MERO use in the high-risk HSCT population.
IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Infections with cytomegalovirus (CMV) and Epstein Barr Virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation (CTOT/CTOTC).
[Show abstract][Hide abstract] ABSTRACT: Cytomegalovirus (CMV) continues to be a significant posttransplant infectious complication after pediatric liver transplant (PLT). The optimal prevention strategy is not currently known. To assess current CMV prevention practices, a web-based survey was conducted within the North American Studies in Pediatric Liver Transplantation (SPLIT) network. Twenty-nine of the 31 centers (94%) surveyed responded. Only seven centers reported evidence-based development of protocols. For most at-risk (donor or recipient CMV seropositive) PLT recipients, a prophylactic strategy predominates current practice. For high-risk (D+/R-), only three centers used nonprophylaxis-based protocols: one preemptive and two sequential/hybrid. Duration of prophylaxis ranged from 84 to 730 days with 14 centers using around 100 days and nine centers using around 200 days. Initial therapy with ganciclovir followed by valganciclovir was the most common strategy. For lower-risk recipients (CMV D-/R-), more centers (10/29) employed a preemptive strategy while the remainder described prophylaxis (15) and sequential/hybrid (3) strategies. Prophylaxis predominates current CMV prevention strategies for at-risk recipients within SPLIT. The variation in duration of therapy provides the opportunity to perform comparative effectiveness studies within SPLIT.
American Journal of Transplantation 06/2014; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recipients of both solid organ transplant and hematopoietic stem cell transplantation are at increased risk for infectious morbidity and mortality after transplantation due to on-going immunosuppression. Gastrointestinal infections have been increasingly reported in these populations.
Increased reports of gastrointestinal infections including bacterial infection with Clostridium difficile, viral infection with norovirus and parasitic pathogens like cryptosporidium are emerging. Risk factors identified have focused on type of transplant, transplant immunosuppression regimens and exposures. Although many events are self-limiting, significant morbidity and rare mortality are reported.
Improved diagnostic techniques have increased the reporting of several gastrointestinal infections after transplantation, affording improved understanding of the epidemiology of these diseases. Armed with this emerging data, prevention, recognition of infection and treatment strategies can be more thoroughly assessed in these at-risk populations.
Current opinion in gastroenterology 11/2013; · 4.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory viruses cause significant morbidity and mortality in immunocompromised populations such as stem cell transplant and solid organ transplant patients. Few viruses causing respiratory tract infection have an approved therapy, and many of the viruses have no therapeutic options at all. In this article, we describe novel agents under development for treatment options against several respiratory viruses.
[Show abstract][Hide abstract] ABSTRACT: Background: Human herpesvirus 6 (HHV-6) is a ubiquitous virus, most children acquire by primary infection by age 2 years. HHV-6 has been associated with serious illness after immune suppression associated with organ transplantation, and is prospectively screened in some institutions after organ transplantation. HHV-6 and the other human betaherpesviruses (cytomegalovirus and HHV-7) have not been well studied in children undergoing cancer chemotherapy. Because these viruses can become latent, finding one during acute illness does not prove a pathogenic role. Our objective was to longitudinally evaluate for the presence of the human betaherpesviruses and EBV from the onset of chemotherapy through the first 2 years after diagnosis of a malignancy in children treated at the CCCH. Methods: We enrolled 77 children with newly diagnosed malignancy requiring chemotherapy and followed prospectively for 2 years. Blood specimens were collected every 2 weeks for the first 6 months, every month for the next 6 months, and then every 3 months. Specimens were also collected during acute illness. DNA was extracted for PCR of HHV-6, HHV-7, CMV and EBV. Samples from each child were run together after all were collected. Analysis was complete-case based and tests were two tailed and performed with SAS 9.2 software. Results: Seventy-three children had evaluable data: 39M/34F with a mean age of 10.1 years (range 6m to 21 y) at enrollment. Deaths: 14; lost to follow up: 3(transferred care). Diagnoses included leukemia/lymphoma (29), histocytosis (3), brain tumor (4), and other (38). There were 159 acute visits in 48 of the children and 907 routine visits in the first year. Of the 48 with acute visits, 31 had +PCR for HHV-6. HHV-6 PCR was + in 10% of both acute and routine visits. HHV-6 was not more likly positive during acute than during a routine visit. HHV-6 viremia was significantly associated with younger age, chemotherapy, and marginally with steroids, but not with acute visits. It was not associated with CMV or EBV reactivation or infection. Conclusion: HHV-6 PCR positivity occurred in a significant proportion of pediatric cancer patients over the course of the first year (51%) of treatment. However it occurred with similar frequency during acute and routine visits. If HHV-6 is not assessed longitudinally clinical events may be misattributed to the virus.
IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
[Show abstract][Hide abstract] ABSTRACT: Background: Respiratory viruses have been linked to bronchiolitis obliterans syndrome in lung transplant recipients. Prospective epidemiology of respiratory viral infections has not been reported in pediatric lung transplant recipients (PLTRs).
Methods: As part of the NIAID-sponsored Clinical Trials in Organ Transplantation in Children (CTOT-C) study of PTLRs, prospective serial nasopharyngeal (NP) and bronchoalveolar lavage (BAL) specimens were interrogated by multiplex PCR (Luminex xTAG®) that identifies 17 viruses. Rhinoviruses and enteroviruses are not differentiated from one another and are referred to here as picornavirus. Sequencing of the picornavirus 5’ non-translated region was performed on samples from patients with multiple picornavirus positive specimens.
Results: 289 NP and 229 BAL specimens from 39 patients were tested. Considering a viral infection to be detection of viral nucleic acid in NP, BAL, or both, 89 infections were detected, of which 73(82%) were picornaviruses. Other viruses detected included: coronaviruses (4); parainfluenza viruses (4); respiratory syncytial virus (3); human metapneumovirus (2); influenza viruses (2); and adenovirus (1). Of the 39 patients, 27(69%) had a least one picronavirus-positive specimen. Of 289 NP specimens, 79(27%) were positive, of which 67(85%) were picornaviruses. Of 229 BAL specimens, 25(11%) were virus-positive, of which 18(72%) were picornaviruses. Of 193 paired NP and BAL specimens, 42 were positive for picornaviruses in one or both specimens. Picornaviruses were detected in the NP only in 26(62%), in BAL only in 4(10%), and in both in 12(29%).
Of note, two patients were picornavirus positive every time they were sampled over a period of time ranging from 13 to 16 months. Sequencing of the 5’ non-translated region of 23 picornoviruses revealed them all to be rhinoviruses. Results revealed both persistent infection with one serotype as well as reinfection with different serotypes.
Conclusion: Picornavirus infections were very common in our population of PLTRs, comprising 82% of all respiratory viral infections detected. Although picornaviruses were the most commonly detected virus, the role of these infections in determining the outcome of pediatric lung transplantation is still uncertain.
IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012
[Show abstract][Hide abstract] ABSTRACT: Background: Staphylococcus aureus (S. aureus) is the predominant organism isolated from children with acute hematogenous osteomyelitis (AHOM). Increasingly, there have been reports of children with AHOM due to CA-MRSA. As the changing microbiologic pattern of AHOM impacts empiric therapy, long-term treatment and outcome, there is a need to identify those patients with AHOM who are at risk for infection with CA-MRSA.
Methods: Cases of pediatric (2 month to 18 years) AHOM treated at our institution from 2007 to 2012 were retrospectively reviewed. Collected data included the demographics, symptoms and signs at presentation, laboratory values, and microbiology results. We compared the clinical and microbiology data for AHOM caused by MRSA to those caused by MSSA and non-MRSA.
Results: AHOM (n=30; ages 6m-17y, median 7y; 16 female) was caused by MSSA (n=12; 40%), MRSA (n=6; 20%), or Group A streptococci (n=2). No pathogen was isolated in 7 patients (23%), all of whom were treated successfully with antimicrobial agents not active against MRSA. The most common affected bones were femur (23%) and tibia (16%). In comparison to patients with MSSA, patients with MRSA infection had a higher rate of bacteremia (100% for MRSA vs. 20% for MSSA, P = 0.009) and more inflammation at presentation evidenced by higher CRP, ESR, neutrophilia, and mean temperature (p = 0.01, 0.04, 0.01, and 0.02; respectively). Personal or family history of skin/soft tissue infection, symptoms and signs at presentation, recent hospitalization or antibiotic use, and co-morbidities were not significantly different between MRSA- and MSSA-infected patients. Comparable results were observed between MRSA- and non-MRSA infected patients (including those with culture negative osteomyelitis), with the exception that ESR was no longer significantly different between the groups. Clindamycin resistance occurred in none of the MRSA and 16% of MSSA isolates.
Conclusion: MSSA remains the most common organism causing AHOM in children at our institution, where an anti-staphylococcal ß-lactam antibiotic remains appropriate empiric therapy. AHOM caused by MRSA is associated with a higher rate of bacteremia, higher fever and more elevated inflammatory markers.
IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012
[Show abstract][Hide abstract] ABSTRACT: Respiratory viruses are common in children, including pediatric recipients of both solid organ transplantation and hematopoietic stem cell transplantation. The prevalence and risk factors in each of these groups are reviewed. Furthermore, associated morbidity and mortality in pediatric transplant recipients with respiratory viral infections are addressed. The literature on specific prevention and treatment options for respiratory syncytial virus, adenovirus, influenza, and other respiratory viruses in pediatric solid organ and hematopoietic stem cell transplant recipients is reported.
[Show abstract][Hide abstract] ABSTRACT: RSV infection can be severe after pediatric lung transplantation. Strategies to prevent and treat RSV in this population are underreported. To assess the current practices, we surveyed the members of the IPLTC regarding RSV prevention and treatment strategies. Twenty-eight programs were surveyed; 18 (64.3%) responded at least partially. A median of 53 transplants (range, 8-355) occurred since inception. RSV testing occurs in asymptomatic (6/17) and symptomatic (17/17) patients. Diagnostic method is polymerase chain reaction at 13 sites and DFA at 8. Transplant candidates were received prophylaxis at 10 sites, with nine following national (5) or local (4) guidelines. All use palivizumab IM and/or IV. Recipients were received prophylaxis with palivizumab at eight centers (eight IM, one IV). Fourteen were treated for RSV (seven all patients; seven age-related). Medications include inhaled (6), oral (4), or IV (4) ribavirin, plus IVIG (9), steroids (8), and IV (2) or IM (3) palivizumab. Prevention and treatment barriers include insurance/hospital concerns, such as institutional reluctance to use inhaled ribavirin. RSV prevention and treatment strategies are diverse at pediatric lung transplant programs. Many centers offer prophylaxis (9/17) and treatments (14/17), but strategies are not uniform.
[Show abstract][Hide abstract] ABSTRACT: Respiratory syncytial virus (RSV) is a significant contributor to morbidity in adult lung transplant recipients. Multiple modes of ribavirin administration have been described in the literature. This study investigated outcomes related to delivery route.
We performed a retrospective analysis of adult lung transplant patients infected with RSV (2006-2010). RSV severity was graded according to clinical symptoms and bronchiolitis obliterans syndrome (BOS) status on International Society for Heart and Lung Transplantation (ISHLT) criteria. Relationships between route of ribavirin delivery and RSV severity, BOS progression at 6 months after RSV infection, and overall survival were assessed. Of 30 RSV-positive patients identified, 9 were ultimately excluded.
The 21 study patients were a mean age of 49 ± 17 years (range, 17-72 years) at transplant. Six received oral and 15 received inhaled ribavirin per clinician preference. No significant differences were observed between the groups by age, sex, or ethnicity. Mean time from transplant to RSV was 26 ± 29 months (range, 1-100 months). Infections were mild in 2 of 6 patients in the oral compared with 11 of 15 in the inhaled group (p = 0.17). None of the oral group and 3 of the inhaled group exhibited BOS 1 at time of infection (p = 0.53); 2 (inhaled) had new onset/progression of BOS at 6 months after RSV (p > 0.99). No difference in overall survival (p = 0.41) was observed between the 2 groups.
This retrospective study demonstrates no significant differences in 6-month outcomes between oral and inhaled ribavirin therapy for RSV infection after lung transplantation.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2012; 31(8):839-44. · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lung transplantation has evolved as an accepted therapy in selected adults and children with end-stage lung disease. Outcomes following lung transplantation have improved in the recent era with a 5-year survival of > 70% and an overall good functional status of surviving recipients. Many of the advances have been achieved by the use of modern immunosuppressive agents. To date, multiple strategies exist that may be employed when utilizing immunosuppression. These agents can be used in a variety of roles that may include induction, maintenance or rescue therapy, many of which are illustrated in this review including the current evidence to support their use. Infections in lung transplant recipients remain a significant cause of morbidity and mortality. Special considerations are required with the substantial burden of chronic infection in candidates with CF lung disease before transplantation, which are discussed. Furthermore, recent progress and advances in prevention and treatment of post-transplantation infectious complications are detailed. Chronic lung allograft dysfunction remains to be the burden of lung transplantation in the long-term. Unfortunately, there is no well-established therapy to address it. However, therapy attempts include change/augmentation of immunosupression, use of neomacrolides and extracorporeal photopheresis, all of which are reviewed in detail.
Current pharmaceutical design 02/2012; 18(5):737-46. · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.
American Journal of Transplantation 10/2011; 11(10):2020-30. · 6.19 Impact Factor