[Show abstract][Hide abstract] ABSTRACT: Aim:
Knowledge of the quality of antimicrobial therapy (AMT) used for invasive healthcare-associated infections (HAIs) in paediatrics is scarce. Influence of the final information about the isolated pathogen on the subsequent targeted AMT was investigated in our study.
Data on 149 children (0-17 years) with blood culture positive HAIs were collected. The causative microbes under investigation were Staphylococcus aureus, Staphylococcus epidermidis, streptococci, Gram negative rods, and mixed infections were likewise included. For adjusting the antimicrobial regimen, an expert panel evaluated the quality of the targeted AMT and the delay of 72 hours after final microbiology results. AMT was regarded as inappropriate if the pathogen was totally resistant to the used antimicrobials (i) or if the chosen therapy was of not optimal efficacy against the pathogen (ii).
17% of the patients received inappropriate AMT. Half of these infections 13/26 (50%) were treated with an antimicrobial to which the isolate was resistant. Three (3/13, 23%) of these patients received antimicrobials which were totally ineffective according to in vitro data. Suboptimal or too broad spectrum AMT was administered to 13/26 (50%) patients. The most common causes of inappropriate use were the use of beta-lactams in oxacillin-resistant Staphylococcus epidermidis infections and vancomycin given in oxacillin-sensitive Staphylococcus aureus infections.
Approximately 17% of the selected cohort received inappropriate AMT. More attention should be paid to the appropriate use of antimicrobials, and training of prescribers should be urgently provided.
PLoS ONE 11/2015; 10(11):e0141555. DOI:10.1371/journal.pone.0141555 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The incidence of invasive Group A Streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nation-wide survey to assess the population-based incidence rates and outcomes of children with iGAS infections.
We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emmtypes or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet.
We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93/100 000 in 1996-2000, 1.80 in 2001-2005, and 2.50 in 2006-2010.The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients weresevere soft tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%), and primary peritonitis (5%). Severe pain was the most typical symptom for soft tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate, 2%.
The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVES:
Selection of the first-dose-in-neonates is challenging. The objective of this proof-of-concept study was to evaluate a pharmacokinetic bridging approach to predict a neonatal dosing regimen.
We selected fluconazole as a paradigm compound. We used data from studies in juvenile mice and adults to develop population pharmacokinetic models using NONMEM. We also develop a physiologically-based pharmacokinetic model from in vitro-in silico data using Simcyp. These three models were then used to predict neonatal pharmacokinetics and dosing regimens for fluconazole.
From juvenile mice to neonates, a correction factor of maximum lifespan potential should be used for extrapolation, while a "renal factor" taking into account renal maturation was required for successful bridging based on adult and in vitro-in silico data. Simulations results demonstrated that the predicted drug exposure based on bridging approach was comparable to the observed value in neonates. The prediction errors were -2.2, +10.1 and -4.6 % for juvenile mice, adults and in vitro-in silico data, respectively.
A model-based bridging approach provided consistent predictions of fluconazole pharmacokinetic parameters in neonates and demonstrated the feasibility of this approach to justify the first-dose-in-neonates, based on all data available from different sources (including physiological informations, preclinical studies and adult data), allowing evidence-based decisions of neonatal dose rather than empiricism.
[Show abstract][Hide abstract] ABSTRACT: SUMMARY In Finland in April 2010, a 3-month old baby was diagnosed with type A infant botulism. He excreted botulinum neurotoxin and/or Clostridium botulinum in his faeces until November 2010. Five months of excretion was after clinical recovery and discharge from hospital. C. botulinum isolates recovered from the household dust in the patient's home were genetically identical to those found in the infant's stool samples. Long-term faecal excretion of C. botulinum may pose a possible health risk for the parents and others in close contact with the infant.
Epidemiology and Infection 05/2013; 142(2):1-5. DOI:10.1017/S0950268813001258 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Assessment of the general status is crucial in the evaluation of a feverish child. It cannot be replaced with any laboratory test. The physician will evaluate the child's general status by examining the level of consciousness, reactions towards the environment, color of the skin, respiratory rate and fluid balance. If the general status has worsened, the child shall immediately be hospitalized. If the symptoms have persisted for more than one day, the CRP value is below 20 mg/l, general status is good, and no signs of bacterial disease are revealed in clinical examination, the condition is most likely a viral infection that will heal by itself.
[Show abstract][Hide abstract] ABSTRACT: Laboratory-based surveillance at a Finnish paediatric tertiary-care centre during the period 1999-2006 identified 739 nosocomial bloodstream infections (BSIs) (1.6 BSIs/1000 patient-days). High rates were detected among haematology patients (4.9 BSIs/1000 patient-days) and neonatology patients (3.2 BSIs/1000 patient-days). Most BSIs (95%) were primary infections, and 75% of those were associated with a central line. The most common pathogens were coagulase-negative staphylococci (52%), Staphylococcus aureus (7%) and Candida species (6%). The overall mortality rate within 7 days after the first positive blood culture was 3%. Those who died were more likely to have been admitted to an intensive-care unit or to have undergone surgery.
[Show abstract][Hide abstract] ABSTRACT: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome.
Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred.
Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy.
Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.
The Journal of pediatrics 09/2007; 151(3):289-92. DOI:10.1016/j.jpeds.2007.03.015 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Legionella pneumophila serogroup 6 was recovered from a bronchoalveolar lavage specimen from a 1-week-old, full-term newborn with pneumonia, as well as from water samples from the maternity hospital and the newborn's home (an apartment). Amplified fragment-length polymorphism typing revealed that the strains isolated from the newborn and her home were indistinguishable from each other but were clearly different from the hospital and control strains. To our knowledge, this is the first report of domestic acquisition of legionnaires disease in a newborn to have been confirmed by molecular typing.
[Show abstract][Hide abstract] ABSTRACT: This study describes the epidemiological association of 3 putative genes for virulence of uropathogenic Escherichia coli; uropathogenic specific protein (usp), a Vibrio cholerae zot gene homologue; IrgA homologue adhesin (iha), a nonhemagglutinating adhesin; and iroN(E. coli), a catechole siderophore receptor homologue. We compared the relative frequency in urinary tract infection (UTI) isolates (n=508), compared with non-UTI isolates (n=416). iroN(E. coli) occurred 2.1-3.6 times more frequently in UTI isolates than in rectal isolates (P=1.1x10-18 to P=2.7x10-5) and was associated with several uropathogenic virulence genes found on pathogenicity islands. usp occurred more frequently in isolates from patients with pyelonephritis (P=3.6x10-9), in periurethral isolates (P=.001), and in isolates from patients with UTI who were aged 40-65 years (P=.004), when compared with the rectal isolates; iha was not associated with UTI in this study.
The Journal of Infectious Diseases 06/2002; 185(10):1521-4. DOI:10.1086/340206 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Seventeen infants with an index episode of pyelonephritis caused by Escherichia coli were monitored for 18 months for recurrent urinary tract infections (UTIs). All the infants had at least 1 recurrent UTI caused by the same pathogen. Twenty-six recurrent UTI episodes were recorded. The 40 E. coli strains available were analyzed by multiplex polymerase chain reaction for 3 alleles (classes I-III) of the papG gene and by pulsed-field gel electrophoresis (PFGE) after genomial digestion by XbaI. Of the 17 index strains, 12 (71%) carried the papG gene; 67% of these strains had class II alleles. In recurrent UTI isolates, the papG-positive E. coli appeared in 16 (70%) of 23 isolates. The proportion of all recurrent isolates available that represented a strain previously encountered (indistinguishable or highly similar in PFGE) in the same infant was 65%. Our results suggest that most recurrent UTIs in infants are endogenous relapses rather than reinfections caused by new organisms.
The Journal of Infectious Diseases 03/2002; 185(3):375-9. DOI:10.1086/338771 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 868 isolates was screened from seven different collections of organisms from previous studies - pyelonephritis in children aged 1-24 months; first, second and recurring urinary tract infection (UTI) in women aged 18-39 years; UTI in women aged 40-65 years and peri-urethral and faecal isolates from women aged 18-39 years - for the presence of 10 potential Escherichia coli UTI virulence genes. Previously reported differences between the frequency of these genes in UTI compared with faecal isolates were confirmed and extended. A single virulence signature (strains containing aer, kpsMT, ompT, fim and papGAD) occurred in 29% of the pyelonephritic isolates, but in no more than 11% of the other collections. Peri-urethral isolates were found to have frequencies of these 10 genes that differed from those found for both UTI and faecal isolates.
Journal of Medical Microbiology 03/2002; 51(2):138-42. DOI:10.1099/0022-1317-51-2-138 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chromosomal genotypes of Escherichia coli isolates from blood, urine and faeces of infants with urosepsis were studied to find possible clonality of the isolates. The isolates were analysed by PCR for class I, II and III alleles of the pyelonephritis-associated adhesin gene papG. The macrorestriction profiles of the papG-positive isolates were analysed by pulsed-field gel electrophoresis and their O serogroups were determined. Genetically identical E. coli isolates from the blood, urine and faeces of the same infant were found in 8 of 10 infants. This finding confirmed the results of previous phenotypic studies that the reservoir of pyelonephritogenic E. coli is indeed the colon.
Journal of Medical Microbiology 08/2001; 50(7):650-2. DOI:10.1099/0022-1317-50-7-650 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants.
A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies.
Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008).
Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.
[Show abstract][Hide abstract] ABSTRACT: A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap. The patient responded well to a course of parenteral penicillin. This is probably the first documented case of community-acquired pneumonia associated with this agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.
[Show abstract][Hide abstract] ABSTRACT: Acute appendicitis is the most common surgical emergency in childhood. However, the pathogenesis and detailed microbiology are obscure.
To determine in detail the bacterial etiology of appendicitis in children in relation to the histologic tissue pathology.
Tissue samples obtained at surgery from 41 children with suspected acute appendicitis were examined histologically and by culture for aerobic and anaerobic bacteria. The patients were analyzed according to histopathologic and clinical findings.
Aerobic and anaerobic species were isolated from 40 of 41 (98%) samples; on average, 14.1 isolates per specimen (10.4 anaerobes and 3.7 aerobes). Specimens from patients with gangrenous appendices yielded significantly higher numbers of anaerobic isolates per specimen than did specimens from patients with healthy appendices (11.7 vs. 7.7; P < 0.01). Bacteria belonging to the Bacteroides fragilis group were the most frequently isolated anaerobic microorganisms (95%). Other organisms frequently isolated in all histology groups were Peptostreptococcus micros (66%), Bilophila wadsworthia (63%), Fusobacterium nucleatum (44%), Eggerthella lenta (44%) and a hitherto undescribed bile-resistant, pigment-producing Gram-negative rod (41%). Of the aerobes Escherichia coli (88%) and Streptococcus anginosus group (former Streptococcus "milleri" group) organisms (61%) were the most frequent findings.
The shift from histologically normal toward gangrenous appendices was clearly associated with markedly elevated anaerobic bacterial counts in terms of species. The unusually high frequencies of B. wadsworthia (75%) and the hitherto undescribed bile-resistant, pigment-producing Gram-negative rod (56%) in gangrenous appendices represent unique and different findings from those reported in adults.
[Show abstract][Hide abstract] ABSTRACT: Invasive fungal infections (IFI) with substantial mortality constitute an increasing problem among BMT patients. From 1986 to 1996 148 children underwent BMT, and are included in a retrospective analysis of the incidence, risk factors and outcome of IFI. By histopathology or culture-proven IFI (Candida, 10; Aspergillus, 8) was documented in 12/73 (16%) allogeneic and in 6/75 (8%) autologous BMT patients. Of these 18 patients, 15 subsequently died, and in 12 (66%) IFI was regarded as the main cause of death. In addition to the patients with documented IFI, 48 had suspected and 82 no fungal infection. Invasive candidal infections were more frequent in patients with semiquantitatively estimated abundant candidal colonization as compared with those with no colonization (18% vs 3%, P = 0.015). In the allogeneic group, 50% of those with severe (grades III-IV) aGVHD had IFI as opposed to 8% of those with no or mild aGVHD (P < 0.001). Regarding cGVHD, 57% of those with extensive cGVHD vs 5% of those with absent or limited cGVHD had IFI (P < 0.001). The dose of steroids was associated with IFI: 77% of those who received high-dose steroids (methylprednisolone 0.25-1 g/day for 5 days) vs 5% of those with conventional-dose (prednisone 2 mg/kg/day) had IFI (P < 0.001). Particularly for BMT patients at risk, new, quicker and better diagnostic tests and more effective anti-fungal agents, both for prophylaxis and treatment, are needed.
Bone Marrow Transplantation 12/2000; 26(9):999-1004. DOI:10.1038/sj.bmt.1702654 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: P-fimbrial genotypes of Escherichia coli strains and their possible association with urinary tract abnormalities were studied in infants with pyelonephritis. A total of 153 urinary E. coli strains were analyzed by polymerase chain reaction for class I, II, and III alleles of the pyelonephritis-associated adhesin gene papG. Strains with any class II papG alleles were found significantly more often in infants with normal anatomy and function or in infants with clinically insignificant abnormalities than they were in infants with significant abnormalities (90 of 119 vs. 14 of 34 infants; P<. 001). On the other hand, strains without any papG alleles were found significantly more often in infants with major urinary tract abnormalities (11 of 34 vs. 17 of 119 infants; P=.016). Our genotypic findings indicate that, especially in infants with a normal urinary tract, infection is caused by more-virulent E. coli than is present in infants without a normal urinary tract. This virulence could be due to expression of pyelonephritogenic P fimbriae by an infecting E. coli strain.
The Journal of Infectious Diseases 05/2000; 181(5):1822-4. DOI:10.1086/315446 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce.
To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers.
A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs.
Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased.
Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings.