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1.  The Influence of Different Fever Definitions on the Rate of Fever in Neutropenia Diagnosed in Children with Cancer 
PLoS ONE  2015;10(2):e0117528.
The temperature limit defining fever (TLDF) is based on scarce evidence. This study aimed to determine the rate of fever in neutropenia (FN) episodes additionally diagnosed by lower versus standard TLDF.
In a single center using a high TLDF (39.0°C tympanic temperature, LimitStandard), pediatric patients treated with chemotherapy for cancer were observed prospectively. Results of all temperature measurements and CBCs were recorded. The application of lower TLDFs (LimitLow; range, 37.5°C to 38.9°C) versus LimitStandard was simulated in silicon, resulting in three types of FN: simultaneous FN, diagnosed at both limits within 1 hour; earlier FN, diagnosed >1hour earlier at LimitLow; and additional FN, not diagnosed at LimitStandard.
In 39 patients, 8896 temperature measurements and 1873 CBCs were recorded during 289 months of chemotherapy. Virtually applying LimitStandard resulted in 34 FN diagnoses. The predefined relevantly (≥15%) increased FN rate was reached at LimitLow 38.4°C, with total 44 FN, 23 simultaneous, 11 earlier, and 10 additional (Poisson rate ratioAdditional/Standard, 0.29; 95% lower confidence bound, 0.16). Virtually applying 37.5°C as LimitLow led to earlier FN diagnosis (median, 4.5 hours; 95% CI, 1.0 to 20.8), and to 53 additional FN diagnosed. In 51 (96%) of them, spontaneous defervescence without specific therapy was observed in reality.
Lower TLDFs led to many additional FN diagnoses, implying overtreatment because spontaneous defervescence was observed in the vast majority. Lower TLDFs led as well to relevantly earlier diagnosis in a minority of FN episodes. The question if the high TLDF is not only efficacious but as well safe remains open.
PMCID: PMC4324993  PMID: 25671574
2.  Adjunctive Daptomycin Attenuates Brain Damage and Hearing Loss More Efficiently than Rifampin in Infant Rat Pneumococcal Meningitis 
Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model.
Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.
PMCID: PMC3421563  PMID: 22644021
3.  Actinobaculum schaalii an emerging pediatric pathogen? 
BMC Infectious Diseases  2012;12:201.
Actinobaculum schaalii was first described as a causative agent for human infection in 1997. Since then it has mainly been reported causing urinary tract infections (UTI) in elderly individuals with underlying urological diseases. Isolation and identification is challenging and often needs molecular techniques. A. schaalii is increasingly reported as a cause of infection in humans, however data in children is very limited.
Case presentation
We present the case of an 8-month-old Caucasian boy suffering from myelomeningocele and neurogenic bladder who presented with a UTI. An ultrasound of the urinary tract was unremarkable. Urinalysis and microscopy showed an elevated leukocyte esterase test, pyuria and a high number of bacteria. Empiric treatment with oral co-trimoxazole was started.
Growth of small colonies of Gram-positive rods was observed after 48 h. Sequencing of the 16S rRNA gene confirmed an A. schaalii infection 9 days later. Treatment was changed to oral amoxicillin for 14 days. On follow-up urinalysis was normal and urine cultures were negative.
A.schaalii is an emerging pathogen in adults and children. Colonization and subsequent infection seem to be influenced by the age of the patient. In young children with high suspicion of UTI who use diapers or in children who have known abnormalities of their urogenital tract, infection with A. schaalii should be considered and empiric antimicrobial therapy chosen accordingly.
PMCID: PMC3457841  PMID: 22928807
Actinobaculum schaalii; Children; Emerging infection; Urinary tract infection; Gram-positive; Antimicrobial susceptibility
5.  A Prospective Multicenter Study of Microbiologically Defined Infections in Pediatric Cancer Patients With Fever and Neutropenia 
Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management.
Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multicenter study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN.
MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared with patients without MDI, fever [median, 5 (interquartile range: 3–8) vs. 2 (interquartile range: 1–3) days, P < 0.001] and hospitalization [10 (6–14) vs. 5 (3–8) days, P < 0.001] lasted longer, transfer to the intensive care unit was more likely [13 of 95 (14%) vs. 7 of 346 (2.0%), P < 0.001], and antibiotics were given longer [10 (7–14) vs. 5 (4–7) days, P < 0.001]. Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but also the purposeful omission of coverage for coagulase-negative staphylococci and enterococci was taken into account [81% (95% confidence interval: 68–90) vs. 96.6% (95% confidence interval: 87–99.4), P = 0.004].
MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.
PMCID: PMC4138005  PMID: 24618935
fever and neutropenia; pediatric oncology; bacteremia; infection

Results 1-5 (5)