Israel Medical Association Journal

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.

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.

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.

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.

 

Abstract

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: HHV6 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.

Background: Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT[1] in Israel is not known.

Objective: To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection.

Methods: Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR[2]. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records.

Results: Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03).

Conclusions: In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT. 

Background: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS[1] status is unknown.

Objectives: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in 35–42 week old neonates born after PROM[2] to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis.

Methods: During a 1 year period, we studied all neonates born beyond 35 weeks gestation with maternal PROM ≥ 18 hours, unknown maternal GBS status and without prior administration of IAP[3]. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR[4].

Results:  Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP[5] > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012–2.6). 

Conclusions: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of ≥ 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Background Voiding cystourethrogram is performed 3–6 weeks after urinary tract infection. This prolongs the interval of prophylactics, reducing the likelihood of performing the procedure.

Objectives To investigate the yield and potential risks/benefits of early compared to late-performance VCUG[1] after UTI[2].

Methods We conducted a prospective study of 84 previously healthy children < 5 years old admitted from October 2001 to November 2002 with first documented UTI. We then divided the 78 patients who had VCUG into two groups and compared them to a control group:  group A – 49 children in whom VCUG was performed within 10 days, group B – 29 children in whom VCUG was performed > 10 days after UTI, and a historical control group C – 82 children in whom VCUG was performed > 4 weeks following UTI.

Results VCUG was performed in 48/48 (100%), 6/35 patients (17.1%), 34/116 patients (29.3%) and vesicoureteral reflux was demonstrated in 38.8%, 37.9%, 39% in groups A, B, C respectively. No significant difference was found between these groups in terms of incidence of VUR[3] and severity and grading of reflux within each group. One case of UTI secondary to VCUG occurred in a patient in whom the procedure was performed 4 months after the diagnosis.

Conclusions Performing VCUG early does not influence detection rate, severity of the VUR, or risk of secondary infection; it shortens the period of prophylactic use and increases performance rate of VCUG, thereby minimizing the risk of failure to detect VUR. The traditional recommendation of performing VCUG 3–6 weeks after the diagnosis of UTI should be reevaluated.

Objectives: To assess the relative efficacy of clinical and laboratory methods in the diagnosis of Bordetella pertussis by patient age and immunization status.

Methods: We compared the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78 recently vaccinated, and 75 post-vaccinated children with suspected pertussis. Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase chain reaction.

Results: PCR[1] and culture identified 41% and 7% of patients with B. pertussis, respectively (P < 0.001). All positive cultures were PCR-positive. Positive PCR was less common among those recently vaccinated than among those in the pre- (P < 0.001) and post-vaccinated groups (P < 0.05). Positive culture was more common among those pre-vaccinated than among those recently vaccinated (P < 0.01). Positive tests for immunoglobulin M and A were more common among the post-vaccinated than the pre- and recently vaccinated (P < 0.001), respectively. Logistic regression analyses revealed that clinical criteria have no significant association with infection in recently and post-vaccinated children. Among the pre-vaccinated children, whoop and cough duration were associated with a positive PCR (odds ratio 7.66 and 0.5, P < 0.001). Seventy-six percent of pre-vaccinated, 39% of recently vaccinated and 40% of post-vaccinated children with positive PCR did not meet the U.S. Centers for Disease Control diagnostic criteria for B. pertussis.

Conclusions: PCR is a useful tool for pertussis diagnosis, particularly in pre-vaccinated infants. The yield of culture and serology is limited, especially among pre- and recently vaccinated children. In pre-vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should be implemented promptly.

Background: Puncture wounds in the feet of children present a clinical dilemma.

Objectives: To evaluate our approach, we reviewed the charts and all available images of 80 children admitted to our institution because of plantar punctures from 1988 to 1999.

Methods: The charts of 80 children were reviewed retrospectively.

Results: Three groups of patients were found: 59 with superficial cellulitis, 11 with retained foreign bodies, and 10 with osteomyelitis and/or septic arthritis. There was a significant presentation delay in patients from the second and third groups. Most common organisms were Staphylococcus aureus or Group A Streptococcus. Of the 80 children, 34 were treated surgically and 46 were treated with antibiotic therapy alone. All patients with osteomyelitis and septic arthritis were re-examined; at follow-up, all but one were asymptomatic apart from residual radiologic sequelae in four.

Conclusions: Patients with an established infection 24–36 hours after a plantar puncture should be admitted to hospital for parenteral antibiotic therapy. Delayed presentation is a significant marker for deep-seated infection. Further infection or relapse after initial improvement suggests the presence of osteomyelitis or a retained foreign body. A bone scan is advisable in all patients with suspected osteomyelitis: a positive bone scan necessitates aggressive early debridement combined with appropriate antibiotics; while negative bone scan, X-ray and exploration suggest that the infection is due to a foreign body, which can be detected by computed tomography.
 

Background: Factors influencing the oral flora of premature infants have not been adequately investigated.

Objective: To investigate the effects of gestational age and of anti-bacterial therapy on the oral flora of premature infants.

Methods: Oral cultures were obtained at age 1 day and age 10 days from 65 premature infants, divided into three groups: a) 24 neonates of 30-34 weeks gestation who did not receive ABT, b) 23 neonates of 30-34 weeks gestation who received ABT, and c) 18 neonates < 30 weeks gestation who received ABT.

Results: Oral bacterial colonization increased from day 1 to day 10 of life. In 24-34 week neonates, gestational age did not affect early bacteremia or oral colonization at birth. Neither gestational age nor ABT affected late bacteremia or oral colonization at day 10. In 30-34 week neonates with ABT, the oral flora consisted mainly of non-Escherichia coli gram-negative bacteria, whereas those who did not receive ABT grew mainly alpha-hemolytic streptococci, Klebsiella pneumoniae and E. coli in neonates < 30 weeks who received ABT the oral flora were mainly coagulase-negative staphylococci. Oral colonization with anearobes was zero and colonization with fungi was minimal.

Conclusions: Acquistion of oral bacteria rose from day 1 to day 10 of life, regardless of gestational life or ABT. On day 10 of life, the spectrum of oral bacterial flora changed following ABT and consisted mainly of coagulase-negative Staphylococcus and non E. coli garm-negative bacteria. Oral colonization showed few fungi but no anaerobes. These microbiologic observations merit attention when empirical anti-microbial therapy is considered in premature infants suspected or having late-onset sepsis.