Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen.

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.

Candida lusitaniae fungemia is a serious infection rarely reported in children. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents. The higher rate of infection in recent years is in need of further investigation.

Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Revaccination of children with acute lymphoblastic leukemia following completion of chemotherapy.

BACKGROUND: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy. METHODS: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination. RESULTS: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster. CONCLUSIONS: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated.

SARS-CoV-2 and seasonal influenza: similarities and disparities.

This report describes the differences in disease severity and clinical presentation between hospitalized patients with coronavirus disease 2019 (COVID-19) and others with seasonal influenza. A total of 136 influenza and 152 COVID-19 patients were included. Patients with influenza more frequently had dyspnea (p = 0.004), hypoxemia (p < 0.001), underlying diseases (p = 0.046), and elevated liver enzymes (p = 0.028). In contrast, patients with COVID-19 were overweight (p < 0.001), lymphopenic (p < 0.001), had elevated CRP (p = 0.011), and radiological abnormalities (p < 0.001). Patients with influenza were more severely ill on admission (NEWS > 5) (p < 0.001). However, length of hospital stay, ventilatory support, and 30-day-mortality were similar. Despite differences in clinical presentation and disease severity between influenza and COVID-19 patients, both groups had similar clinical outcomes.

Evaluation of Pediatric Screening for Resistant Pathogens in an Israeli Tertiary Center.

BACKGROUND: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality. OBJECTIVES: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations. METHODS: Data were collected from all patients under 18 years who met our internal guidelines from 2015-2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample. RESULTS: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34). CONCLUSIONS: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.

The epidemiology of Staphylococcus aureus bacteraemia in Israeli children: Community- vs hospital-acquired or healthcare related infections.

AIM: Incidences of Staphylococcus aureus bacteraemia (SAB) in Israeli children are unknown. The characteristics of SAB in children have not been evaluated. METHODS: SAB from children aged ≤18 years old, admitted to a tertiary hospital in Israel during 2002-2015, were included. The proportional rate of SAB was calculated per 1000 admissions. SAB were classified as community acquired (CA), hospital acquired (HA) and healthcare related (HCR). Patients' characteristics, antibiotic susceptibility and outcomes were assessed in each group. RESULTS: The rate of SAB was stable, 1.48 per 1000 admissions. HA, CA and HCR-SAB comprised 53%, 25% and 22%, respectively. Only 27/185 (14.6%) were caused by methicillin-resistant S aureus (MRSA): 22%, 6% and 5% of HA, CA and HCR-SAB, respectively. Central venous catheter, recent surgery, immunodeficiency and age <6 years were the main risk factors for HA and HCR-SAB (adjusted OR: 68.9, 7.5, 5.8 and 5.5, respectively). Treatment duration for CA was >21 days: and for HA and HCR, 14-20 days. All-cause in-hospital mortality and 30-day mortality were documented in 10 (5%) and 3 (2%) episodes, respectively. CONCLUSION: The rate of SAB; the proportions of CA, HA and HCR-SAB; and the proportion of MRSA was stable over the years. MRSA was mainly in HA-SAB. Thirty-day mortality was rare.

Q Fever Osteoarticular Infection in Children.

Q fever osteoarticular infection in children is an underestimated disease. We report 3 cases of Q fever osteomyelitis in children and review all cases reported in the literature through March 2018. A high index of suspicion is encouraged in cases of an unusual manifestation, prolonged course, relapsing symptoms, nonresolving or slowly resolving osteomyelitis, culture-negative osteomyelitis, or bone histopathology demonstrating granulomatous changes. Urban residence or lack of direct exposure to animals does not rule out infection. Diagnosis usually requires use of newer diagnostic modalities. Optimal antimicrobial therapy has not been well established; some case-patients may improve spontaneously or during treatment with a ß-lactam. The etiology of treatment failure and relapse is not well understood, and tools for follow-up are lacking. Clinicians should be aware of these infections in children to guide optimal treatment, including choice of antimicrobial drugs, duration of therapy, and methods of monitoring response to treatment..

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51-9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24-9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47-60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01-40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.

Adenovirus Respiratory Infection among Immunocompetent Patients in a Pediatric Intensive Care Unit During 10-year period: Co-morbidity is common.

BACKGROUND: Adenovirus is responsible for 2-7% of childhood viral respiratory infections, 5-11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection. OBJECTIVES: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU). METHODS: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both. RESULTS: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months-11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died. CONCLUSIONS: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

Containment of a Methicillin-resistant Staphylococcus aureus (MRSA) Outbreak in a Neonatal Intensive Care Unit.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a challenging nosocomial pathogen in the last 50 years. OBJECTIVES: To describe an investigation and containment of an MRSA outbreak in a neonatal intensive care unit (NICU). METHODS: Our NICU is a 25-bed level III unit. Almost 540 neonates are admitted yearly. The index case was an 8 day old term baby. MRSA was isolated from his conjunctiva. Immediate infection control measures were instituted, including separation of MRSA+ carriers, strict isolation, separate nursing teams, and screening of all infants for MRSA. Healthcare workers and parents of positive cases were screened and re-educated in infection control measures. New admissions were accepted to a clean room and visiting was restricted. MRSA isolates were collected for molecular testing. RESULTS: MRSA was isolated from five infants by nasal and rectal swabs, including the index case. Screening of healthcare workers and families was negative. Two MRSA+ patients already known in the pediatric intensive care unit (PICU) located near the NICU were suspected of being the source. All NICU isolates were identical by pulsed-field gel electrophoresis but were different from the two PICU isolates. The NICU and one of the PICU isolates were defined as ST-5 strain by multilocus sequence typing. One PICU isolate was ST-627. All NICU isolates were Panton-Valentine leukocidin negative and SCCmec type IV. No further cases were detected, and no active infections occurred. CONCLUSIONS: A strict infection control policy and active screening are essential in aborting outbreaks of MRSA in the NICU.

Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel.

Candida auris and C. haemulonii are closely related, multidrug-resistant emerging fungal pathogens that are not readily distinguishable with phenotypic assays. We studied C. auris and C. haemulonii clinical isolates from 2 hospitals in central Israel. C. auris was isolated in 5 patients with nosocomial bloodstream infection, and C. haemulonii was found as a colonizer of leg wounds at a peripheral vascular disease clinic. Liberal use of topical miconazole and close contact among patients were implicated in C. haemulonii transmission. C. auris exhibited higher thermotolerance, virulence in a mouse infection model, and ATP-dependent drug efflux activity than C. haemulonii. Comparison of ribosomal DNA sequences found that C. auris strains from Israel were phylogenetically distinct from isolates from East Asia, South Africa and Kuwait, whereas C. haemulonii strains from different countries were closely interrelated. Our findings highlight the pathogenicity of C. auris and underscore the need to limit its spread.

Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone.

Patients with infantile spasms, an intractable epileptic disorder, often are treated with adrenocorticotropic hormone. Legionella pneumophila is a rare cause of pneumonia in children. We describe 2 infants with Legionella pneumonia whose infection occurred within 1 month after starting adrenocorticotropic hormone.

Comparative Characteristics of the 2009 Pandemic Influenza A (H1N1) Virus and 2010-2011 Seasonal Influenza in Pediatric Patients.

BACKGROUND: In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2. OBJECTIVES: To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic. METHODS: A retrospective observational study was conducted at a tertiary hospital. Data were collected from the medical records of all children who were hospitalized from April 2009 to 2011 with laboratory-confirmed influenza. RESULTS: Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62 had seasonal influenza, and 29 had H1N1 in 2010-2011. Patients with the 2009 H1N1 were characterized by older age, more co-morbidity conditions and more symptoms including fever, cough and rhinitis on admission. No significant differences in outcomes between the groups were recorded. Of patients hospitalized with pandemic influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of patients hospitalized with seasonal influenza in 2010-11. Children with pandemic influenza received more oseltamivir (Tamiflu®) (94% vs. 19.4%, P < 0.001) and more antibiotics than the other groups. CONCLUSIONS: The type of influenza had no effect on outcome. There were no significant differences between groups in the percentages of in-hospital mortality, admission to intensive care units, prolonged hospitalization (> 9 days), or the development of complications during hospitalization.

Children hospitalised with influenza-associated pneumonia during the 2009 pandemic displayed increased disease severity.

AIM: The precise role of the influenza virus in the morbidity of hospitalised paediatric pneumonia cases is unknown. We identified how many cases hospitalised during the 2009 pandemic had influenza-associated pneumonia and assessed their severity. METHODS: Children admitted to three Israeli medical centres during the 2009 influenza pandemic with radiologically confirmed pneumonia were prospectively screened for influenza. We compared the clinical, laboratory and radiologic findings for positive and negative cases. RESULTS: The pandemic H1N1 virus was detected in 89 (30%) of the 297 patients hospitalised for pneumonia and 55% of the Paediatric Intensive Care Unit admissions for pneumonia. There were no significant differences in the rates of underlying disease between the two groups. Logistic regression analysis revealed that children with pandemic H1N1 virus-associated pneumonia had significantly increased disease severity than those without, with a higher incidence of hypoxemia (41.6% versus 24%) with a relative risk (RR) of 2.2, higher rate of paediatric intensive care unit admission (16.9% versus 5.8%, RR of 2.7) and higher rate of mechanical ventilation (10.1% versus 2.4%, RR:4.4). CONCLUSION: During the 2009 influenza pandemic, 30% of children hospitalised for pneumonia had the influenza infection and these children displayed increased disease severity.

Serum galactomannan screening for diagnosis of invasive pulmonary aspergillosis in children after stem cell transplantation or with high-risk leukemia.

Both transplanted and leukemia patients are at high risk (HR) for invasive pulmonary aspergillosis (IPA). Methods for rapid diagnosis are crucial. Our objective was to investigate the impact of serial serum galactomannan assay (GMA) screening on IPA diagnosis in children. Between January 2010 and December 2011, all children following stem cell transplantation (SCT) or with HR leukemia were prospectively included. Serum samples for GMA were taken once-twice weekly. Results >.5 were considered positive. Patients suspected of having IPA were stratified as possible, probable, and definite. Forty-six children (median age, 8 years) were included, 38 after SCT (32 allogeneic), 8 with HR leukemia. A total of 510 samples were taken; screening period was 1-6 months for 34 patients. GMA was negative in 28 patients, all but one without suspicion of IPA. Eighteen patients had positive GMA: while four (22%) were upgraded to probable IPA, fourteen (78%) were considered as false positives (FP), some associated with piperacillin-tazobactam treatment. GMA sensitivity and specificity were 0.8 and 0.66, respectively; positive- and negative-predictive values (PPV, NPV) were 0.22 and 0.96, respectively. GMA may have a role in evaluating HR children for IPA. Both NPV and FP rates are high. The cost benefit of early detection versus over-diagnosis should be further studied.

Human Herpes Virus-6 Following Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear. OBJECTIVE: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT. METHODS: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006-June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations. RESULTS: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load. CONCLUSIONS: HHV-6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

Detection, control, and management of a respiratory syncytial virus outbreak in a pediatric hematology-oncology department.

BACKGROUND: Immunocompromised patients are at increased risk for severe respiratory syncytial virus (RSV) infection. Palivizumab is approved for prevention of RSV in specific populations but not for treatment. Few studies demonstrated the safety and successful treatment with intravenous (IV) palivizumab. We describe our experience with IV palivizumab treatment for RSV in a pediatric hematology-oncology department during an outbreak. METHODS: During a short period of renovations, oncology patients were placed in a general pediatric ward. After a case of severe fatal RSV pneumonia in a 2-year-old male patient with acute myeloid leukemia, all patients were actively screened twice weekly regardless of symptoms. Respiratory samples were tested for RSV using rapid immunochromatography detection, immunofluorescence, or reverse transcriptase polymerase chain reaction. A single dose of palivizumab (15 mg/kg) was given to children below 3 years of age who tested positive for RSV. RESULTS: Over a 6-week period, 12 patients tested positive for RSV. Seven patients were treated with palivizumab. Five patients had respiratory symptoms, and 2 were asymptomatic. No adverse events were attributed to IV palivizumab treatment. Early-treated patients had no complications attributed to RSV. CONCLUSIONS: Containment of RSV outbreak in high-risk children is difficult. Screening with reverse transcriptase polymerase chain reaction and the early use of IV palivizumab is safe and may prevent complications of RSV infection among these patients.

Molecular-based diagnosis of bacteremia in the setting of fever with or without neutropenia in pediatric hematology-oncology patients.

BACKGROUND: Prompt evaluation and appropriate treatment with wide-spectrum antibiotics is considered mandatory for febrile oncology patients especially during neutropenia. Central venous catheters are widely used in pediatric oncology patients and are often the source of infections. Patients are usually admitted for follow-up and administration of antibiotics. Aims were to assess the efficacy of the polymerase chain reaction (PCR) method in identifying bacteria in blood samples as compared with standard blood cultures. METHODS: This was a prospective study, which included all patients with central venous catheters admitted to the pediatric hematology-oncology department over the 14-month period. Demographic, clinical, and laboratory variables were compared in bacteremic and nonbacteremic patients. Standard microbiological cultures were compared using the PCR technique. RESULTS: From September 2004 to November 2005, 148 blood cultures (70 patients) were evaluated. Positive blood cultures were detected on 21 (18.3%) occasions. PCR had sensitivity of 46%, specificity of 98%, positive predictive value 86%, and negative predictive value 89%. The PCR identified fastidious bacteria in 2 occasions when standard cultures were negative. CONCLUSIONS: Inspite of low sensitivity, PCR may help with early identification of bacteremia. Improving this technology is warranted.

Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel.

OBJECTIVES: We studied profile of the bloodstream infections (BSI) in the pediatric intensive care unit (PICU) and identified predictors of mortality. METHODS: The study collected data from hospital records for children younger than 18-years who developed BSI during their PICU stay between 2014 and 2019. RESULTS: In 114 patients, 136 PICU-acquired BSIs with 152 pathogens were documented. The incidence of BSI was 47.12/1,000 PICU admissions and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates, Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10, CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels (P=0.029) were associated with increased risk of ICU mortality. CONCLUSION: BSI in the PICU is associated with increased mortality. Early identification and management of risk factors independently associated with poor clinical outcomes in these patients should be aimed to ensure improved survival.