Pneumocystis carinii pneumonia: Pitfalls of prophylaxis

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.     

Variability of Pneumocystis jirovecii prophylaxis use among pediatric solid organ transplant providers

Pneumocystis jirovecii pneumonia (PJP) prophylaxis after pediatric solid organ transplant (SOT) is routinely recommended, but practice varies. Online survey was sent in 2018 to 707 members of the International Pediatric Transplant Association. A total of 105 responded, representing 47 institutions in 18 countries consisting of transplant physicians (66%), transplant surgeons (19%), nurse practitioners (6%), infectious disease physicians (5%), or pharmacists (4%). PJP prophylaxis was reported by 88%, while 12% did not routinely give prophylaxis. The majority not using PJP prophylaxis performed renal transplants (67%) citing low incidence of PJP (62%). Trimethoprim/sulfamethoxazole was first‐line agent (95%). PJP prophylaxis for 4‐6 months was the most frequent duration following kidney (48%, 27/56), liver (42%, 13/31), and heart (40%, 10/25) transplant. Abdominal multivisceral providers equally gave 10‐12 months (47%) or lifelong (47%); most lung transplant providers gave lifelong prophylaxis (85%). Across all organs, 21% provided lifetime prophylaxis. After completion of prophylaxis, 32% do not restart for any reason; majority of the rest would restart for treatment of acute graft rejection. 83% reported no PJP cases in the prior 12 months; 14% reporting 1‐5 infections. Only 3% reported a case of PJP infection on prophylaxis; none in SOT. PJP prophylaxis is routinely provided to pediatric SOT patients though practice and duration vary by center and organ type. Durations of 4‐6 months were most common for renal, liver, and heart transplant recipients, while 10‐12 months or lifelong prophylaxis were commonly reported for abdominal multivisceral recipients and most lung transplant recipients are given lifelong prophylaxis.     

Pneumocystis carinii pneumonia in a girl with a midbrain glioma

A 7-year-old girl with a midbrain glioma contracted Pneumocystis carinii pneumonia (PCP) the absence of cytotoxic or corticosteroid therapy. Gliomas are known to cause immunosuppression, in and PCP prophylaxis should be considered for patients with these tumors.     

Antiinfectious prophylaxis in pediatric oncology. Work group "Quality Assurance" of Society for Pediatric Oncology and Hematology (GPOH)]

Infections in disease- and/or chemotherapy-related neutropenia are major, often emergency-type problems in the treatment of pediatric oncology patients and explain the ongoing discussion about antiinfectious prophylaxis. The different aspects of prophylaxis and an overview on the literature are presented. Antiinfectious prophylaxis in pediatric oncology includes the following issues: 1. General aspects such as information for patients and parents on neutropenia and risk of infectious diseases and indication and management of reverse isolation and barrier isolation; 2. antibacterial prophylaxis with oral non-absorbable and oral absorbable antibiotics; 3. Pneumocystis carinii (Pc) prophylaxis; 4. antifungal prophylaxis to prevent disseminated candidiasis and aspergillosis; 5. antiviral prophylaxis, especially varicella-zoster-virus (VZV) post-exposure prophylaxis and cytomegalovirus (CMV) prophylaxis; 6. immunoglobulins and hematopoietic growth-factors (HGF); 7. active immunization. An evaluation of those measures leads to the following conclusions: A major controversy exists regarding antibacterial and antifungal prophylaxis. Probably not effective are the use of reverse isolation and of oral, non-absorbable antibiotics. Oral absorbable antibiotics, antifungal prophylaxis using fluconazole and amphotericin B and the use of hematopoietic growth factors are likely to be effective. Clearly effective are strict hand-washing procedures, Pc and CMV prophylaxis and passive vaccination against VZV in case of VZV exposure of a seronegative patient.     

An outbreak of Pneumocystis carinii pneumonia in children with malignancy

An outbreak of Pneumocystis carinii pneumonia (PCP) in three patients within a 6 week period was reported. Two patients had acute lymphoblastic leukaemia and one had brain-stem glioma. They shared common features of immuno-suppression and absence of cotrimoxazole prophylaxis and had been nursed in the same room. The severity of PCP and its response to treatment may be related to the degree of immunosuppression. Because of the morbidity and mortality of PCP, chemoprophylaxis should be given to all at-risk cases. Furthermore, isolation of patients with PCP should be considered in view of increasing evidence of nosocomial transmission.     

Prophylactic antibiotics in pediatric surgery

The frequency and appropriateness of prophylactic antibiotic use in children less than 6 years of age who received surgery were examined. Antibiotics were prescribed for 62% of children who had surgery, and prophylaxis was the sole reason for antibiotic use in 73% of the patients. Prophylactic antibiotics were administered inappropriately with respect to timing or duration to 42% of the children receiving preoperative prophylaxis, 67% receiving intraoperative prophylaxis, and 55% receiving postoperative prophylaxis. Thus, prophylaxis alone is the major indication for antibiotic use in pediatric surgical patients, and prophylactic antibiotics are frequently administered inappropriately.     

Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis

We report on a 10-y-old boy who developed Pneumocystis carinii pneumonitis (PCP) as the dominant symptom at the onset of haemophagocytic lymphohistiocytosis (HLH). PCP is a common infection in patients with combined primary immunodeficiencies or acquired immunodeficiency syndrome but it has rarely been observed at the onset of HLH. Typically, HLH presents as a febrile syndrome associated with cytopenia and hepatosplenomegaly. Repeated bone marrow aspirates, spleen or lymph node biopsies are sometimes required to reveal haemophagocytosis. Because of the significant immunosuppression during treatment of HLH, prophylaxis of PCP with co-trimoxazole is recommended. However, de-arranged immune response in HLH renders the patients susceptible to opportunistic infections, even before the introduction of immunosuppressants. Conclusion: We suggest that in patients with unclear respiratory symptoms, it is worth considering a differential diagnosis of HLH.     

Antifungal prophylaxis in pediatric lung transplantation: An international multicenter survey

Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal infection prevention strategies. It was the aim to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. A self‐administered, web‐based survey on current practices to prevent fungal infection was circulated to centers within the IPLTC. Twenty‐one (88%) IPLTC centers participated, predominantly from Europe and the US. More than 50% of respondents perform adult and pediatric lung transplant operations. Twenty‐four percent use universal prophylaxis, 28% give prophylaxis to all patients but stratify the antifungal coverage based on pretransplant risk, and 48% target prophylaxis to only the children with CF or pretransplantation fungal colonization. Commonly, centers aim to target Aspergillus and Candida infection. Monotherapy with either voriconazole or inhaled amphotericin B is used in the majority of centers. Institutions utilize prophylactic therapy for variable time periods (40% 3–6 months; 30% ≥12 months). Alternative drugs were prescribed for lack of tolerance, toxicity, or positive surveillance culture. TDM (itraconazole/voriconazole) was used in 86% of centers. The survey revealed a wide range of antifungal prophylaxis strategies as current international practice in pediatric lung transplant recipients.     

Wait list status of pediatric dialysis patients in North America

Kidney transplantation is the treatment of choice for the majority of pediatric patients with end-stage kidney disease. Previous studies demonstrating racial or gender disparities in access to the deceased donor transplant list could not evaluate the impact of medical concerns or patient preference on waitlist status. We undertook a retrospective cohort study using the NAPRTCS registry to begin to determine barriers to wait list registration for kidney transplantation among pediatric dialysis patients. Clinical and demographic factors were compared in listed vs. non-listed patients. Reasons cited for not listing patients were examined by clinical and demographic factors. At dialysis initiation, 88.7% of pediatric dialysis patients were not on the renal transplant wait list. Twelve months after dialysis initiation, 67.1% of pediatric dialysis patients were not on the wait list. The groups least likely to be on the wait list were infants (adjusted OR 0.23, 95% CI 0.16, 0.32) and girls (adjusted OR 0.78, 95% CI 0.67, 0.90) after adjusting for multiple confounders. The reason most often cited for not listing was medical reason for young infants and that the transplant workup was pending for girls. Further study is needed to identify barriers to wait list registration.     

Role of flexible bronchoscopy in the diagnosis of pulmonary infiltrates in pediatric patients with cancer

We reviewed 60 consecutive flexible bronchoscopies done during a 36-month period in 48 pediatric cancer patients with undiagnosed pulmonary infiltrates. Diagnostic procedures during bronchoscopy included 40 brushings, 50 bronchoalveolar lavages, and 6 transbronchial and mucosal biopsies. A total of 16 specific diagnoses were made by bronchoscopy (27% diagnostic yield), including infection (12), pulmonary leukemia (3), and lymphoma (1). The largest proportion of specific diagnoses came from lavage (14/50) and the smallest from brushings (1/40). Biopsies were also useful for selected patients. The low overall yield for bronchoscopy was probably due to the routine use of empiric broad-spectrum antibiotics and antifungal therapy, as well as trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonitis. Subsequent specific diagnoses were obtained by other procedures (open biopsy, needle aspiration, or autopsy) for 10 patients with negative bronchoscopy results and 3 patients with diagnostic bronchoscopies. These additional diagnoses included 7 infections (Pneumocystis carinii (1), Candida tropicalis (1), cytomegalovirus (1), and Aspergillus (4), and 6 other diagnoses with nonspecific histologic findings. A positive bronchoscopy result may be useful, but negative bronchoscopy findings do not justify delaying other diagnostic procedures or discontinuing antibiotic and antifungal therapy in children with cancer and pulmonary infiltrates.     

儿童肾病合并肺孢子菌肺炎3例临床分析

目的 提高对肺孢子菌肺炎(PCP)的认识.方法 回顾分析3 例肾病并发PCP患儿的临床资料.结果 3例患儿的共同特点是,PCP起病急,临床以发热、咳嗽起病,伴有低氧血症,症状与体征不平行;早期临床表现无特异性,易漏诊,并发PCP前患儿均长期或大量应用免疫抑制剂、足量泼尼松口服疗程达8周及以上;免疫功能检查均有不同程度的CD4细胞比例下降.结论 提高对PCP的认识,做到早期诊断;适当控制免疫抑制剂应用、改善患儿生活环境、针对高危人群定期检测CD4细胞水平以及酌情应用复方磺胺甲基异噁唑预防均有利于降低肺孢子菌肺炎的发病率.     

Growth factor practice patterns among pediatric oncologists: results of a 1998 Pediatric Oncology Group Survey. Economic Evaluation Working Group the Pediatric Oncology Group

The American Society of Clinical Oncology (ASCO) guidelines on growth factor (GF) use recommend applying adult-derived guidelines in pediatric oncology. An ASCO survey of adult oncology GF use determined the preference for first degree prophylaxis (use of GF when febrile neutropenia [FN] is expected to be high in untreated patients), second-degree prophylaxis (administration of GF after a documented episode of FN on a previous cycle of chemotherapy), and intervention in the treatment of FN. Similar preferences have not been evaluated in pediatrics. The purpose of this study was to (1) characterize GF use in pediatric oncology; (2) correlate use patterns with demographic factors; and (3) compare the Pediatric Oncology Group (POG) and ASCO surveys. The ASCO survey was revised for use within pediatric oncology and was mailed to the physician membership of POG; 341 were returned (86% completion rate). Comparisons were made with the ASCO survey. Most (76%) physicians said GF use was determined by protocol requirements and most (70%) patients were entered on POG protocols. GF use as first-degree prophylaxis was selected 40% of the time, which was significantly greater than in adults; this was most influenced by anticipated duration of neutropenia (> or =7 days). The severity of the initial clinical course (e.g., neutropenia, infection) influenced use in second-degree prophylaxis; dose reduction alone was never selected. For FN, GF use was 45%, with lower preferences in uncomplicated FN (16%-38%) compared with complicated FN (66%). POG respondents endorse greater use of GF for first-and second-degree prophylaxis but less use in uncomplicated FN than do ASCO respondents. These patterns may reflect different strategies, including the role of chemotherapy, value of dose intensity, and perceived toxicity of regimens. Given these differences, adult-based guidelines may not be appropriate for pediatrics.     

Random practice patterns of surgical antimicrobial prophylaxis in neonates

Antimicrobial prophylaxis accounts for 75% of antibiotic use on pediatric surgical services, but controlled, prospective studies evaluating surgical prophylaxis in neonates are lacking. We surveyed pediatric surgeons at 21 centers to: (1) determine practice patterns in neonatal surgical prophylaxis and treatment of necrotizing enterocolitis (NEC), and (2) assess whether a prospective study evaluating the efficacy of a single agent in place of a multiple drug regimen would be indicated, practical, and have the potential to effect a positive change in practice patterns. Surgeons responded concerning prophylactic regimens for common congenital anomalies and treatment of NEC. The most common regimen was an ampicillin/gentamicin combination (55% to 82%), while 23% added clindamycin for contaminated alimentary tract cases and 41% added clindamycin for NEC. There was wide variation in dosage and duration of coverage. A prospective study would determine whether antimicrobial monotherapy provides equal or better clinical results than an ampicillin/gentamicin regimen; whether there are cost savings associated with monotherapy; and whether a shorter treatment scheme would be effective, safe, and feasible. Correspondence to: M. E. Fallat     

OPEN LUNG BIOPSY IN CHILDREN WITH DIFFUSE PULMONARY LESIONS

ABSTRACT. During the period 1973-81, open lung biopsy was performed in 33 consecutive children, aged 1 month to 13 years, to exclude or diagnose Pneumocystis carinii pneumonia and to differentiate other interstitial pulmonary lesions. Twenty-one of the patients were undergoing immunosuppressive treatment because of their malignant disease. The clinical diagnosis was correct only in 55% of the patients, but open lung biopsy and histological examination gave the final answer in every patient. Pneumocystis carinii was the causative organism in 67 % of the immunosuppressed patients. Nine patients had postoperative complications, 5 of which were mild in nature and resolved spontaneously. Three patients had to be reoperated on for postoperative sequelae. There was one death possibly caused by surgical intervention–tension pneumothorax 10 days after surgery. It is concluded that open lung biopsy is the most reliable method in the diagnosis of diffuse interstitial pneumonitis in children. The need of anaesthesia is no contra-indication and the benefits of the biopsy far outweight the risks of its complications.     

Exploring the Attitudes of Pediatric Oncologists Toward the Use of Laxatives for the Prevention of Constipation in Patients Undergoing Active Treatment: A Canadian Perspective

Background: Constipation is a common problem in pediatric oncology patients and may lead to significant consequences. There is a paucity of the published literature on the prevention of constipation in this population. The primary purpose of this study was to explore the current practice of pediatric oncologists in preventing constipation in children receiving active chemotherapy treatment, specifically during periods of intensive vincristine therapy. Methods: A Web-based survey of pediatric oncologists and pediatric oncology trainees in Canadian centers was conducted. Results: A 48% response rate was achieved. The majority of physicians had a lower threshold for defining constipation in oncology patients compared with the published literature. More than 90% of the respondents estimated the prevalence of constipation in pediatric oncology patients to be 30% or higher. The majority of respondents prescribed constipation prophylaxis in the presence of one or more of the following factors: history of constipation prior to or during previous phases of therapy, vincristine combined with either narcotics or immobility, multiple vincristine doses per month, spinal cord compression and immobility, and isolated narcotic therapy. Polyethylene glycol 3350, lactulose, and ducosate were the most commonly recommended first-line prophylactic therapies used. Conclusion: Constipation is a significant problem in patients during cancer treatment. Most oncologists suggest giving laxatives as prophylaxis in the presence of risk factors, as well as prompt treatment once any symptoms appear. Our results suggest a role for the introduction of guidelines in the prevention of constipation, especially for patients receiving frequent vincristine therapy.     

Bloodstream infections in pediatric ECLS: usefulness of daily blood culture monitoring and predictive value of biological markers. The British Columbia experience

Introduction  The incidence of bloodstream infection (BSI) in extracorporeal life support (ECLS) is reported between 0.9 and 19.5%. In January 2006, the Extracorporeal Life Support Organization (ELSO) reported an overall incidence of 8.78% distributed as follows: respiratory: 6.5% (neonatal), 20.8% (pediatric); cardiac: 8.2% (neonatal) and 12.6% (pediatric). Method  At BC Children’s Hospital (BCCH) daily surveillance blood cultures (BC) are performed and antibiotic prophylaxis is not routinely recommended. Positive BC (BC+) were reviewed, including resistance profiles, collection time of BC+, time to positivity and mortality. White blood cell count, absolute neutrophile count, immature/total ratio, platelet count, fibrinogen and lactate were analyzed 48, 24 and 0 h prior to BSI. A univariate linear regression analysis was performed. Results  From 1999 to 2005, 89 patients underwent ECLS. After exclusion, 84 patients were reviewed. The attack rate was 22.6% (19 BSI) and 13.1% after exclusion of coagulase-negative staphylococci (n = 8). BSI patients were significantly longer on ECLS (157 h) compared to the no-BSI group (127 h, 95% CI: 106–148). Six BSI patients died on ECLS (35%; 4 congenital diaphragmatic hernias, 1 hypoplastic left heart syndrome and 1 after a tetralogy repair). BCCH survival on ECLS was 71 and 58% at discharge, which is comparable to previous reports. No patient died primarily because of BSI. No BSI predictor was identified, although lactate may show a decreasing trend before BSI (P = 0.102). Conclusion  Compared with ELSO, the studied BSI incidence was higher with a comparable mortality. We speculate that our BSI rate is explained by underreporting of “contaminants” in the literature, the use of broad-spectrum antibiotic prophylaxis and a higher yield with daily monitoring BC. We support daily surveillance blood cultures as an alternative to antibiotic prophylaxis in the management of patients on ECLS.     

非人类免疫缺陷病毒感染儿童重症肺孢子菌肺炎七例临床分析

目的:探讨小儿肺孢子菌肺炎(pneumocystis jirovecii pneumonia,PCP)的临床特征,提高儿科医师对该病的认识。方法:回顾性分析西安市儿童医院儿童重症监护病房(pediatric intensive care unit,PICU)2019年1月至12月收治的7例非人类免疫缺陷病毒感染PCP患...     

Methemoglobinemia associated with dapsone therapy in a child with pneumonia and chronic immune thrombocytopenic purpura

This report describes a case of methemoglobinemia in association with dapsone therapy. The patient, an immunocompromised child with chronic immune thrombocytopenic purpura, presented with fever, cough, perioral cyanosis, bilateral lower lobe rales, and low O2 saturation by pulse oximetry (89%). His medications included prednisone and rituximab for chronic immune thrombocytopenic purpura, and dapsone for Pneumocystis carinii pneumonia prophylaxis. Because of his lack of dyspnea and tachypnea, and the temporal association of his perioral cyanosis with the initiation of dapsone therapy, a methemoglobin (MetHb) level was obtained and found to be elevated at 9.6%. The authors discuss the mechanism and treatment of methemoglobinemia secondary to dapsone. They also stress the importance of monitoring for signs and symptoms of methemoglobinemia in immunocompromised patients on dapsone therapy for P. carinii pneumonia prophylaxis.     

GCV/VCVG prophylaxis against CMV DNAemia in pediatric renal transplant patients: A systematic review and meta‐analysis

CMV disease continues to stand as a significant threat to the longevity of renal transplants in children. More pediatric recipients are CMV‐negative with CMV‐positive donor serologies resulting in a HR mismatch. The length of prophylaxis with GCV or VGCV required to optimally prevent recurrence of CMVDNAemia remains unknown. This study is a meta‐analysis comparing GCV/VGCV prophylaxis regimens provided for <6 months, from 6 to <12 months, and ≥12 months after transplant in order to prevent CMVDNAemia. The search conducted involved PubMed, EMBASE, ISI Web of Science, and Cochrane Central Register from inception through December 2017. Search terms Kidney Transplantation, CMV, GCV, and VGCV provided 204 studies for abstract review. Studies excluded were those which did not itemize pediatric data separately, single case reports, and duplicate studies. Pooled analysis of five retrospective studies and one prospective study identified that there is no statistically significant difference in the incidence of CMV DNAemia when comparing <6 months of prophylaxis and >12 months of prophylaxis (23% and 15%, respectively, P = 0.23). Regardless of the length of prophylaxis, there was no statistical difference in the incidence of CMV DNAemia in the HR patients (6 to <12 months vs <6 months, P = 0.62; 6 to <12 months vs ≥12 months, P = 0.78; ≥12 months vs <6 months, P = 0.83). This study identifies no optimal length of prophylaxis for HR mismatch pediatric renal transplant patients as many develop CMV DNAemia.