Efectos de la vacuna neumocócica conjugada (VCN7 y VCN13) en los niños turcos con enfermedad neumocócica invasiva: experiencia en un solo centro / The effects of pneumococcal conjugate vaccine (PCV7 and PCV13) on Turkish children with invasive pneumococcal disease: a single center experience

Introducción: Nuestro objetivo fue determinar los cambios en la incidencia de enfermedad neumocócica invasiva (ENI), la distribución de serotipos y patrones de resistencia antibiótica del Streptococcus pneumoniae en niños con ENI tras el período de vacunación (de 1 a 7 años) con vacuna neumocócica de 7 serotipos (VCN7) (2008) y de 13 serotipos (VCN13) (2011). Población y métodos: El estudio se realizó en 39 niños con ENI de 1 mes a 18 años de edad en Angora, Turquía. Se identificó Streptococcus pneumoniae en sangre, líquido cefalorraquídeo, líquido pleural, y otros tejidos y líquidos corporales estériles mediante procedimientos estándar. Se analizó la resistencia de cepas aisladas de S. pneumoniae a penicilina y ceftriaxona con la prueba de epsilometría (E-test). Los serotipos de las cepas se determinaron con la reacción de Quellung. Resultados: La incidencia anual de ENI disminuyó significativamente de 7,71 (intervalo de confianza --#91;IC--#93; del 95%: de 1,99 a 13,4) a 1,58 (IC del 95%: de 0,6 a 3,77; reducción del riesgo relativo= -79,5; p= 0,006) cada 100 000 habitantes de < 5 años de edad sin enfermedad preexistente. Durante todo el período del estudio, los serotipos en la VCN7 y en la VCN13 representaron el 27,8% y el 63,8% de las cepas aisladas, respectivamente. Los serotipos en la VCN13 correspondían al 81,8% de los casos de ENI en la era previa a la introducción de esta vacuna, y disminuyeron al 56% en los cuatro años posteriores. Las tasas de resistencia a penicilina y ceftriaxona (en el caso de la meningitis) fueron del 48,5% y el 9,1%, respectivamente. Conclusiones: Este estudio observó una disminución significativa en la incidencia de ENI después de la introducción de la VCN13.

Introduction. The aim of this prospective singlecenter study was to determine the changings in incidence of invasive pneumococcal disease (IPD), serotype distribution and the antimicrobial resistance patterns of S. pneumoniae in children with IPD after the period (1 to 7 years) of vaccination with PCV7 (2008) and PCV13 (2011). Population and methods. The study was conducted on 39 Turkish children with IPD between ages 1 month and 18 years in Ankara, Turkey. Streptococcus pneumoniae was identified using standard laboratory procedures from blood, cerebrospinal fluid (CSF), pleural fluid, and other sterile body fluids and tissues. S. pneumoniae isolates were tested for resistance to penicilin and ceftriaxone using the E-test methodology. Serotypes of the isolates were determined by Quellung reaction. Results. The overall annual incidence rate of IPD decreased significantly from 7.71 (95% CI, 1.99-13.4) to 1.58 (95% CI, 0.6-3.77; RRR= -79.5; p= 0.006) per 100 000 population among <5 years of age without underlying disease. During the overall study period, the PCV7-serotypes and PCV13-serotypes represented 27.8% and 63.8% of isolates, respectively. PCV13-serotypes made up 81.8% of cases of IPD in the pre-PCV13 era and decreased to 56% in the 4 years after PCV13. The penicillin and ceftriaxone (for meningitis) resistance rates were 48.5% and 9.1%, respectively. Conclusions. This is the first study about the changing pattern of the incidence of IPD in Turkish children after the implementation of the PCV7 and PCV13 in Turkish national vaccine schedule and a prominent decrease in incidence of IPD has seen after the implementation of PCV13.

The effects of pneumococcal conjugate vaccine (PCV7 and PCV13) on Turkish children with invasive pneumococcal disease: a single center experience. / Efectos de la vacuna neumocócica conjugada (VCN7 y VCN13) en los niños turcos con enfermedad neumocócica invasiva: experiencia en un solo centro.

INTRODUCTION: The aim of this prospective single-center study was to determine the changings in incidence of invasive pneumococcal disease (IPD), serotype distribution and the antimicrobial resistance patterns of S. pneumoniae in children with IPD after the period (1 to 7 years) of vaccination with PCV7 (2008) and PCV13 (2011). POPULATION AND METHODS: The study was conducted on 39 Turkish children with IPD between ages 1 month and 18 years in Ankara, Turkey. Streptococcus pneumoniae was identified using standard laboratory procedures from blood, cerebrospinal fluid (CSF), pleural fluid, and other sterile body fluids and tissues. S. pneumoniae isolates were tested for resistance to penicilin and ceftriaxone using the E-test methodology. Serotypes of the isolates were determined by Quellung reaction. RESULTS: The overall annual incidence rate of IPD decreased significantly from 7.71 (95% CI, 1.99-13.4) to 1.58 (95% CI, 0.6-3.77; RRR=-79.5; p=0.006) per 100 000 population among ≤5 years of age without underlying disease. During the overall study period, the PCV7-serotypes and PCV13-serotypes represented 27.8% and 63.8% of isolates, respectively. PCV13-serotypes made up 81.8% of cases of IPD in the pre-PCV13 era and decreased to 56% in the 4 years after PCV13. The penicillin and ceftriaxone (for meningitis) resistance rates were 48.5% and 9.1%, respectively. CONCLUSIONS: This is the first study about the changing pattern of the incidence of IPD in Turkish children after the implementation of the PCV7 and PCV13 in Turkish national vaccine schedule and a prominent decrease in incidence of IPD has seen after the implementation of PCV13.

INTRODUCCIÓN: Nuestro objetivo fue determinar los cambios en la incidencia de enfermedad neumocócica invasiva (ENI), la distribución de serotipos y patrones de resistencia antibiótica del Streptococcus pneumoniae en niños con ENI tras el período de vacunación (de1 a 7 años) con vacuna neumocócica de 7 serotipos (VCN7) (2008) y de 13 serotipos (VCN13) (2011). POBLACIÓN Y MÉTODOS: El estudio se realizó en 39 niños con ENI de 1 mes a 18 años de edad en Angora, Turquía. Se identificó Streptococcus pneumoniae en sangre, líquido cefalorraquídeo, líquido pleural, y otros tejidos y líquidos corporales estériles mediante procedimientos estándar.Se analizó la resistencia de cepas aisladas de S. pneumoniae a penicilina y ceftriaxona con la prueba de epsilometría (E-test). Los serotipos de las cepas se determinaron con la reacción de Quellung. RESULTADOS: La incidencia anual de ENI disminuyó significativamente de 7,71 (intervalo de confianza [IC] del 95%: de 1,99 a 13,4) a 1,58 (IC del 95%: de 0,6 a 3,77; reducción del riesgo relativo=-79,5; p=0,006) cada 100 000 habitantes de ≤ 5 años de edad sin enfermedad preexistente. Durante todo el período del estudio, los serotipos en la VCN7 y en la VCN13 representaron el 27,8% y el 63,8% de las cepas aisladas, respectivamente. Los serotipos en la VCN13 correspondían al 81,8% de los casos de ENI en la era previa a la introducción de esta vacuna, y disminuyeron al 56% en los cuatro años posteriores. Las tasas de resistencia a penicilina y ceftriaxona (en el caso de la meningitis) fueron del 48,5% y el 9,1%, respectivamente. CONCLUSIONES: Este estudio observó una disminución significativa en la incidencia de ENI después de la introducción de la VCN13.

Successful treatment of multidrug-resistant Escherichia coli bacteremia with tigecycline in an acute myeloid leukemia child.

The multidrug-resistant bacterial infections cause high mortality in immunocompromised patients because of the limited antibacterial choices. Tigecycline, first member of the glycylcyclines, has in vitro activity against a wide variety of organisms, including multidrug-resistant pathogens; however, it has not yet been approved for use in children. Herein, we report a nine-year-old girl with acute myeloid leukemia who was treated successfully with tigecycline due to multidrug-resistant Escherichia coli bacteremia.

Nosocomial infections due to Acinetobacter baumannii in a pediatric intensive care unit in Turkey.

The aim of this study is to document the clinical characteristics and outcomes of Acinetobacter baumannii infections in pediatric patients in a pediatric intensive care unit (PICU) in Turkey. The ages ranged from 1 month to 16 years with a mean age of 55.5 months, and the male-to-female ratio was 1:1.5. Ventilator-associated pneumonia (10 patients) was the leading diagnosis, followed by catheter-related blood stream infection (4 patients), and bacteremia and ventilator-associated pneumonia associated with meningitis (1 patient) due to A. baumannii. Mechanical ventilation (93.3%), central venous catheter (73.3%), urinary catheter (93.3%), and broad spectrum antibiotic usage (80%) were the frequently seen risk factors. Neuromuscular (40%) and malignant (26.7%) disorders were the most common underlying diseases. Nosocomial A. baumannii is commonly multidrug-resistant, prolongs the length of stay in the PICU and increases the mortality rates in pediatric critical care.

Urinary tract infections owing to ESBL-producing bacteria: microorganisms change--clinical pattern does not.

AIM: Urinary tract infections (UTIs) caused by extended-spectrum beta lactamase (ESBL)-producing bacteria have become a growing problem worldwide. The aim of this study was to investigate the clinical and radiological findings in patients with community-acquired UTIs owing to ESBL-producing bacteria. METHODS: Files of the patients that had UTI owing to ESBL-producing bacteria, between January 2008 and December 2009, were retrospectively evaluated. RESULTS: One hundred and eleven UTI episodes in 94 patients were included. Seventy-five per cent of the patients had recurrent UTIs. Ultrasound, dimercaptosuccinic acid (DMSA) scintigraphy and voiding cystourethrography (VCUG) were found abnormal in 36%, 46% and 31% of the patients, respectively. Overall, 68% of the patients had ≥1 underlying predisposing factor for UTI. Male patients and acute pyelonephritis (APN) episodes were more frequent at small ages. The rate of female patients and cystitis episodes predominated with increasing age. Ultrasound, DMSA scintigraphy, VSUG and UT abnormalities were more frequent in patients with APN, and lower UT disturbances were more frequent in patients with cystitis. CONCLUSION: UTIs owing to ESBL-producing bacteria begin to replace UTIs owing to non-ESBL-producing bacteria. However, the clinical pattern of these infections does not seem to be different. Thus, our aim should be to correct underlying predisposing factors in general in order to prevent infections owing to ESBL-producing bacteria.

Invasive Candida infections in children: the clinical characteristics and species distribution and antifungal susceptibility of Candida spp.

The aims of the study were to examine the distribution of Candida spp. isolated from sterile body sites, the antifungal susceptibility of the isolates to amphotericin B, fluconazole, voriconazole, and caspofungin, and factors affecting mortality with invasive Candida infections in children. Thirty-five children with invasive candidiasis between January 2004 and January 2008 were evaluated retrospectively. The antifungal susceptibility of isolated Candida species was studied by Etest. Of the invasive Candida infections, 65.7% were due to C. albicans. The second most common isolated species was C. parapsilosis (11.4%). The rates of resistance to fluconazole, amphotericin B and voriconazole were 8.5%, 2.8% and 5.7%, respectively. Caspofungin was the most effective antifungal agent. 22.8% of the patients died in the first 30 days. In univariate analyses, increased mortality was associated with stay in the intensive care unit, the presence of central venous catheter (CVC), failure to remove CVC, and mechanical ventilation.

Asymptomatic catheter related Rhizobium radiobacter infection in a haploidentical hemapoetic stem cell recipient.

Catheter related infections are reported as one of the most common source of nosocomial infections. Rhizobium radibacter infections are generally manifested by fever and leukocytosis. Here, a 14 months-old girl diagnosed as T (-) B (-) NK (+) severe combined immunodeficiency (SCID) is presented. She had received repeated (x3) unconditioned haploidentical hematopoetic stem cell transplantations. During the follow-up, she has been arised an asymptomatic infection with R. Radiobacter, which was isolated from central venous catheter and peripheral blood while she was clinically stable, free of symptoms, fever or leukocytosis. She was treated successfully with cefepime and amikacin and did not require catheter removal. So, it is once more clear that the blood cultures should be obtained on regular basis from all patients with an intravascular device, even they were asymptomatic.

A rapid lateral flow stool antigen immunoassay and (14)C-urea breath test for the diagnosis and eradication of Helicobacter pylori infection in children.

Our aim was to evaluate diagnostic accuracy of rapid immunochromatographic stool antigen test (Rapid HpSA; LINEAR Chemical, Barcelona, Spain) and a practical low-dose (14)C urea breath test (UBT) (Heliprobetrade mark) test before and after eradication therapy. One hundred nine children with abdominal symptoms (age range, 5-17 years; mean, 12.1) underwent endoscopy, (14)C-UBT, and Rapid HpSA. Patients were defined as Hp infected when histology was positive for Hp. Forty children (36.6%) were Hp infected. The sensitivity of Rapid HpSA and (14)C-UBT was 65% and 92.5% (P = 0.0003), respectively; the specificity of Rapid HpSA and (14)C-UBT was 92.3% and 85.5% (P = 0.180), respectively. After eradication therapy endoscopy, (14)C-UBT and Rapid HpSA were repeated. The eradication rate was 70.5%. After eradication, the sensitivity of Rapid HpSA and (14)C-UBT was 60% and 100%, respectively; the specificity of Rapid HpSA and (14)C-UBT was 100%. (14)C-UBT was more reliable than the Rapid HpSA test for the diagnosis and for confirming eradication of Hp infection.

Stenotrophomonas maltophilia bacteraemia in Turkish children.

BACKGROUND: Stenotrophomonas maltophilia is an important cause of life-threatening nosocomial infection. AIM: To evaluate the clinical features, antibiotic treatment and prognosis of S. maltophilia bacteraemia. METHODS: Patients with blood cultures positive for S. maltophilia at the Children's Hospital, Ankara University Medical School between 1995 and 2005 were evaluated retrospectively. The results were compared with those of a case-control group of patients with Pseudomonas aeruginosa bacteraemia (n=33). Antibiotic susceptibilities of S. maltophilia strains were determined by disc diffusion. Susceptibility to ciprofloxacin was also determined by broth dilution. RESULTS: Thirty-six (2.2%) blood cultures were positive for S. maltophilia. Neutropenia was more common in the P. aeruginosa group (p=0.001). Breakthrough bacteraemia developed more commonly during carbapenem treatment in the S. maltophilia group (p=0.02). Ciprofloxacin and trimethoprim-sulfamethoxazole in combination with/without an aminoglycoside were the antibiotics most commonly selected to treat S. maltophilia bacteraemia. Mortality was more common in the P. aeruginosa (13/33) than in the S. maltophilia (2/33) group (p=0.001). According to susceptibility, determination by the disk diffusion method, beta-lactam antibiotics, aminoglycosides and chloramphenicol had little or no effect, whereas trimethoprim-sulfamethoxazole, doxycycline and fluoroquinolones were more active against S. maltophilia strains. However, ciprofloxacin susceptibility results were quite different when determined by disk diffusion (97% isolates susceptible) and broth dilution (49% isolates susceptible). CONCLUSIONS: Although S. maltophilia bacteraemia is rare in children, antibiotic resistance to these strains is an important problem. Tetracyclines, trimethoprim-sulfamethoxazole and fluoroquinolones are the most active agents against S. maltophilia strains.

Antibiotic resistance of urinary tract pathogens and evaluation of empirical treatment in Turkish children with urinary tract infections.

The changing pattern of antimicrobial resistance in the causative microorganisms of urinary tract infection (UTI) in childhood is a growing problem. The aims of this study were to assess the resistance patterns of urinary isolates to commonly used antimicrobials and to evaluate the options for empirical treatment of UTI. A prospective cross-sectional analysis of bacteria isolated from children with UTI was performed between January 2003 and January 2004. Resistance to antibiotics was analysed in three age groups: Group I, < or =12 months; Group II, 13-60 months; and Group III, >60 months. A total of 165 urinary pathogens were isolated from 131 patients. Mean patient age was 63.7+/-49.8 months. The most common causative agent was Escherichia coli (87% of cases) followed by Klebsiella pneumoniae (10%). Resistance to ampicillin (74.2%) and co-trimoxazole (61.3%) was significant in all isolates. Nitrofurantoin was the most active agent against E. coli (2.2% resistant isolates), followed by amikacin (4.9%), ceftriaxone (7.5%) and ciprofloxacin (12%). None of the isolates from Group I patients were resistant to ciprofloxacin and a low resistance rate (7.1%) was noted for amikacin. In Group II patients, none of the isolates were resistant to amikacin, and ceftriaxone was the second most suitable antibiotic (resistance rate 2.2%). In Group III patients, the lowest resistance rate was against nitrofurantoin (2.7%). In conclusion, we observed that the use of ampicillin and co-trimoxazole as a single agent for empirical treatment of a suspected UTI would not cover the majority of urinary pathogens in our region. Whilst amikacin, with a negligible resistance rate, was suitable in all age groups, gentamicin might still be useful as an empirical treatment of UTI in children aged >1 year. Nitrofurantoin could be included as a reasonable alternative in the empirical treatment of lower UTI in older children.

PCR evaluation of false-positive signals from two automated blood-culture systems.

Rapid detection of micro-organisms from blood is one of the most critical functions of a diagnostic microbiology laboratory. Automated blood-culture systems reduce the time needed to detect positive cultures, and reduce specimen handling. The false-positive rate of such systems is 1-10%. In this study, the presence of pathogens in 'false-positive' bottles obtained from BACTEC 9050 (Becton Dickinson) and BacT/Alert (Biomérieux) systems was investigated by eubacterial and fungal PCR. A total of 169 subculture-negative aerobic blood-culture bottles (104 BacT/Alert and 65 BACTEC) were evaluated. Both fungal and eubacterial PCRs were negative for all BACTEC bottles. Fungal PCR was also negative for the BacT/Alert system, but 10 bottles (9.6%) gave positive results by eubacterial PCR. Sequence analysis of the positive PCR amplicons indicated the presence of the following bacteria (number of isolates in parentheses): Pasteurella multocida (1), Staphylococcus epidermidis (2), Staphylococcus hominis (1), Micrococcus sp. (1), Streptococcus pneumoniae (1), Corynebacterium spp. (2), Brachibacterium sp. (1) and Arthrobacter/Rothia sp. (1). Antibiotic usage by the patients may be responsible for the inability of the laboratory to grow these bacteria on subcultures. For patients with more than one false-positive bottle, molecular methods can be used to evaluate the microbial DNA in these bottles. False positives from the BACTEC system may be due to elevated patient leukocyte counts or the high sensitivity of the system to background increases in CO(2) concentration.

Multi-resistant viridans streptococcal pneumonia and sepsis in the ventilated newborn.

Mechanical ventilation increases the frequency of nosocomial infections. This study describes the frequency of multi-resistant viridans streptococcal colonisation, the clinical course of nosocomial sepsis and ventilator-associated pneumonia in mechanically ventilated neonates in the neonatal intensive care unit of Ankara University Hospital. Seventy-nine ventilated newborns were enrolled. Broncho-alveolar lavage culture and blood cultures were positive in 44 (56%) and 17 (22%) patients, respectively. The most predominant micro-organisms in broncho-alveolar lavage cultures were multi-resistant viridans streptococci (29, 66%). Viridans streptococci were also one of the predominant organisms in blood cultures (5/17, 29%). In 29 patients with broncho-alveolar lavage positive for viridans streptococci, nine (31%) had colonisation, 15 (52%) had ventilator-associated pneumonia and five (17%) had sepsis owing to viridans streptococcus. Ventilator-associated pneumonia was encountered in 52/1000 ventilation days. Mortality was caused by infection in three (10%) of them. Mechanically ventilated neonates in our neonatal intensive care unit had a high rate of both multi-resistant viridans streptococcus airway colonisation and subsequent ventilator-associated pneumonia and sepsis.

The possible role of intrauterine infections in unexplained second trimester abortions and macerated stillbirths: a study from a single center.

OBJECTIVE: To investigate the role of intrauterine infections in unexplained second trimester abortions and stillbirths. STUDY DESIGN: Histopathologic and microbiologic evidence of intrauterine infection in the placentas, fetal membranes and fetal lung tissues of 18 unexplained second trimester abortions and macerated stillbirth cases as well as the placentas and fetal membranes of 10 healthy term neonates were investigated in a prospective study conducted in Ankara University School of Medicine, Turkey. RESULTS: Histopathologic chorioamnionitis and placental culture positivity rates in the study and control groups were 64.7 vs 0%. Bacteria were recovered from 90.9% of placentas and 36.4% of fetal lungs of the cases with histopathologic chorioamnionitis. Intrauterine infection was found in 66.7% of the whole study group, in 85.7% of the unexplained second trimester abortions, and in 54.5% of the macerated stillbirths. CONCLUSION: Intrauterine infection may be an important factor in unexplained stillbirths and second trimester abortions in centers where pregnancy follow-ups lack evaluation for asymptomatic infection.

The validity of diagnostic criteria for streptococcal pharyngitis in Integrated Management of Childhood Illness (IMCI) guidelines.

The WHO's Integrated Management of Childhood Illness (IMCI) programme is being implemented in Turkey with an additional section relating to throat problems for our country's adaptation. The aim of this study is to evaluate the validity of this additional part and suggest new combinations for the diagnosis of streptococcal pharyngitis to improve the guidelines. Throat swabs were obtained from 245 children between 0 and 17 years of age with signs and symptoms of upper respiratory tract infections. Considering the throat culture based diagnosis as the gold standard, the validity of the symptoms alone and in combinations were calculated. The combination in Turkey's IMCI guideline was found to be 36.9 per cent sensitive and 68.3 per cent specific. Sensitivities of combinations including at least two of the following three symptoms, namely sore throat, pharyngeal erythema, and pharyngeal exudates or sore throat, pharyngeal erythema, and fever, were 76.9 and 87.7 per cent, respectively. Specificities of the same combinations were 49.4 and 30.6 per cent. We concluded that new combinations with a higher sensitivity may be considered as a criterion for antibiotic treatment.

Investigation of risk factors for tonsillopharyngitis with macrolide resistant Streptococcus pyogenes in Turkish children.

BACKGROUND: Streptococcus pyogenes is the most important causative agent of tonsillopharyngitis. Although penicillin is the drug of choice in streptococcal tonsillopharyngitis, macrolides are recommended drugs in patients who have an allergy to penicillin. However, resistance to macrolides is an important problem in some regions of the world. Risk factors for resistance development have not been investigated sufficiently. OBJECTIVES: To investigate the risk factors for the development of tonsillopharyngitis with macrolide resistant S. pyogenes. METHODS: Three hundred and forty-five children with tonsillopharyngitis caused by S. pyogenes were investigated for various risk factors. Streptococcus pyogenes isolated from children's throat culture were examined for erythromycin, clarithromycin and azithromycin susceptibility. RESULTS: Two hundred and sixty-three children were found eligible for the analysis of risk factors. Resistances to erythromycin, clarithromycin and azithromycin were detected as 3.8, 4.2 and 4.2%, respectively. Macrolide use of the family members in the last 3 months (odds ratio = 7.04, P = 0.005) has been determined to be a risk factor for the development of tonsillopharyngitis with macrolide resistant S. pyogenes. CONCLUSION: Restriction of macrolide antibiotic use appears to be the most important measure to prevent the development of tonsillopharyngitis with resistant S. pyogenes.

Investigation of Candida dubliniensis in Candida spp.-positive hemocultures.

Candida dubliniensis is one of the Candida species which was first recognized in 1995. The yeast was misidentified because of its phenotypic similarities with Candida albicans. In this study, blood samples of patients from various departments at Ankara University Medical Faculty between January 1996 and September 2000 were investigated for distribution of Candida spp. and presence of C. dubliniensis. Ninety-eight culture positive fungi were included in the study. Phenotypic tests for identification of C. dubliniensis and tests for differentiation of the yeast from C. albicans, such as colony morphology on Staib agar, growth at 42 degrees C and 45 degrees C, beta-glucosidase activity and carbohydrate assimilation, were carried out. Sixty-four of the isolates produced germ tubes and chlamydospores, and none of them had the phenotypic characteristics of C. dubliniensis. Further large-scale studies of specific patient groups are necessary to reveal the etiologic importance of this yeast.