Piperacillin/tazobactam plus amikacin versus carbapenem monotherapy as empirical treatment of febrile neutropenia in childhood hematological malignancies.

A prospective, randomized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia. Patients aged 2-16 years with hematological malignancies who had febrile neutropenia were randomly assigned to receive piperacillin/tazobactam (80 mg/kg piperacillin/10 mg/kg tazobactam, q6h) combined with amikacin (PTA) (7.5 mg/kg, q12h) or meropenem or imipenem (20 mg/kg, q8h) (C). Response to antimicrobial therapy, evaluated for etiological agents, was measured. Duration of fever, neutropenia, and hospitalization, mortality, and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups. Out of 87 febrile neutropenic episodes that were evaluable for comparison, 46 patients received PTA and 41 patients were treated with carbapenems (imipenem or meropenem). Overall, the microbiologically documented infection rate was 21.9%, with Staphylococcus epidermidis as the most common cause of bacteremia. The rate of treatment modification was 56.5% in the PTA group and 53.6% in the carbapenem group with no statistical difference (p > .05). There was no infection-related mortality during the study period. There was no difference between the two regimens for durations of fever, neutropenia, and hospitalization (p > .05 for all categories). PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies.

Long-term beneficial effects of dexamethasone on intellectual and neuropsychological outcome of children with pneumococcal meningitis.

A Substantial ratio of bacterial meningitis survivors suffers mild or serious intellectual and neuropsychological handicaps. We organized eighty subjects into three groups: 1) Pneumococcal meningitis (PM) who did not receive dexamethasone, 2) PM who received dexamethasone, 3) Other bacterial meningitis with different etiology. All subjects underwent Bender Visual Motor Gestalt test and age-appropriate Intelligence quotient (IQ) tests. The mean full-scale IQ scoring fell within normal range (90+/-17) in the post-meningitic cohort. There was no statistical difference between two pneumococcal groups regarding full scale IQ testing (88+/-16 and 91+/-18) and Bender-Gestalt scoring (4.0+/-3.3 and 3.8+/-2.6), respectively. However, the subjects with full scale IQ score <85 (below the average) were statistically less in the group with steroid therapy. PM patients who received dexamethasone therapy had statistically better academic performance. As a result, adjuvant steroid therapy has no significant impact on overall intellectual tests in PM subjects. However, dexamethasone seems to diminish development of below the average IQ scoring in PM cases. In addition, PM subjects who received steroids showed better academic achievement. These findings may support the idea of dexamethasone administration prior to first antibiotic dose in PM subjects.

Primary hemophagocytic lymphohistiocytosis in Turkish children.

Nineteen children with hemophagocytic lymphohistiocytosis (HLH) were studied in the Department of Pediatric Hematology, Hacettepe University. Patients were divided into two groups. Group 1: Thirteen patients were classified as having a genetic etiology (7 familial, 6 presumed familial) on the basis of an affected sibling and consanguinity. There was a history of consanguineous marriage in 13 of the families. Seven of them had a history of a sibling with HLH. Group 2: Six patients were diagnosed with sporadic HLH. The age at presentation for familial patients was 0.7-84 months (mean 21.9 +/- 24.9 months), and for sporadic cases it was 2.5-48 months (mean 22.7 +/- 19.8 months). The clinical and laboratory data of these two groups were similar at diagnosis. Thirteen cases were diagnosed premortem by bone marrow aspiration. Splenic biopsy was performed in 2 patients. Four patients were diagnosed by postmortem examination. Elevated LDH levels were found in all patients tested. No significant differences for clinical and laboratory data were found between the two groups.

Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.

The purpose of this study was to compare meropenem monotherapy with combination therapy for empirical treatment of neutropenic fever in children with lymphoma and solid tumors. Ninety episodes of neutropenic fever in children (0.7-16.0; mean age 7.7 years) with solid tumors in a single center were randomized to receive either meropenem (50 mg/kg/dose-maximum 1 g, every 8 hours) or piperacillin (200 mg/kg/dose, every 6 hours) plus amikacin (15 mg/kg daily). Failure was defined as treatment modification. Non-Hodgkin's lymphoma (NHL) accounted for 62.2 percent of all episodes, and solid tumors (37.8%) for the rest. Blood cultures were positive in 23 percent of all episodes. Sixty-seven percent of all isolated microorganisms stained Gram-positive. Overall success was 70.0 percent (63/90). The success with meropenem was comparable to that seen with piperacillin plus amikacin: 76.6 versus 64.6 percent (p = 0.25). The failure rate was 33 percent with Gram-positive culture and 78 percent with Gram-negative or mixed cultures. The solid tumor group had significantly less bacteremia (4/34 versus 17/56; p < 0.05) and treatment failure (3/34 versus 24/56; p < 0.001) than the NHL group. No serious drug-related adverse event was noticed. Meropenem monotherapy was as effective as piperacillin plus amikacin combination in the empirical treatment of neutropenic fever in children with lymphoma and solid tumors.

Salmonella septic arthritis in a patient with acute idiopathic thrombocytopenic purpura treated with steroid.

Salmonella has three clinical presentations: self-limiting gastroenteritis, a systemic syndrome (enteric or typhoid fever), and bacteremia with focal infection. Hematogenous infections can cause focal lesions, but unusual manifestations occur more often when predisposing factors such as T cell defect, hemolytic disorders (sickle cell disease, malaria) or trauma are present. Salmonella tend to invade bones and joints. There is no mention of acute idiopathic (immune) thrombocytopenic purpura as a predisposing factor for salmonella septic arthritis; however there are reports about the importance of platelets for the immune response. Here we present a case of Salmonella enteritidis septic arthritis following acute idiopathic (immune) thrombocytopenic purpura in a 15-year-old female patient who has been on steroid therapy for the last two weeks.

Leukocytoclastic vasculitis in a child with epidermolysis bullosa simplex.

A 10-year-old boy with epidermolysis bullosa simplex (Weber-Cockayne variant) together with leukocytoclastic vasculitis is presented. He was admitted to the hospital with the provisional diagnoses of infected epidermolysis bullosa simplex or drug eruption. On the sixth day of hospitalization he developed palpable purpura, abdominal pain and bloody diarrhea, together with hematuria and proteinuria. A generalized tonic-clonic convulsion, changes in mental status, fluctuations in arterial blood pressure and intractable pain in his extremities occurred during the course of hospitalization. Systemic pulse steroid therapy, antibiotics, and antihypertensive and anticonvulsive drugs were given. On the 30th day of hospitalization, a skin graft was performed to replace a large tissue defect on his left hand. Despite high dose steroid therapy, his hematuria, proteinuria and hypertension continued after his discharge, suggesting a steroid-resistant renal pathology, such as focal glomerulosclerosis, that occurred secondary to leukocytoclastic vasculitis.

Epidemiology and antibiotic resistance of gram-negative urinary pathogens in pediatric patients.

In order to determine the etiological agents and the rate of resistance to various antibiotics, 209 consecutive gram-negative bacteria isolated from children admitted to Hacettepe University Children's Hospital with urinary tract infections were investigated over a three-month period. Of these, 46 (22%) were nosocomial isolates. The most frequently isolated organism was E.coli (n: 141) followed by Klebsiella spp. (39), Proteus spp. (19), Pseudomonas spp. (8) and Enterobacter spp. (2). In vitro susceptibilities were evaluated by microbroth dilution method, following NCCLS guidelines. Overall, 75 percent of the isolates were resistant to ampicillin, 52 percent were resistant to TMP/SMX and 25 percent to cefuroxime. Amikacin was the most active aminoglycoside; 93 percent of the isolates were susceptible to this agent, while resistance to gentamicin was 21 percent. Resistance to ceftazidime and ceftriaxone was 12 percent and 19 percent, respectively. Overall, resistance to imipenem was one percent and to ciprofloxacin three percent. These in vitro results should be taken into account before initiating empirical therapy; broad spectrum antibiotics should not be used if the isolate is susceptible to the older drugs in order to prevent the increase in resistance.

Recurrent meningitis associated with congenital paravertebral dermal sinus tract.

Recurrent meningitis is a rare but important event that needs to be searched for a predisposing factor. Congenital dermal sinuses occurring in the midline are among the etiological factors. Here, an 18-month-old boy with three attacks of recurrent meningitis due to a paramedian dermal sinus tract is presented. Klebsiella was the cultured causative agent. The lesion was suspected on physical examination and demonstrated by lumbosacral magnetic resonance imaging. To the best of our knowledge, this is the first case in English-language literature of the paravertebrally located dermal sinus tract resulting in recurrent meningitis. Therefore, a careful physical examination, especially including the paravertebral region beside the midline, is essential. Magnetic resonance imaging is a non-invasive descriptive method in the evaluation of congenital dermal sinus tracts.

Hypokalemic paralysis in association with acute gastroenteritis: a report of a sporadic case.

Hypokalemic periodic paralysis is a condition, characterized by episodic weakness of the skeletal muscle. It may be presented as familial or sporadic (secondary). In sporadic cases, the patient may present with paralysis without any previous self or familial history. It is known that these patients are more susceptible to hypokalemia than normal individuals. In low serum K+ concentrations that the normal population can tolerate, these patients may easily suffer from paralysis. A sporadic case of hypokalemic quadriparesis associated with acute gastroenteritis without any self or family history is reported. The patient had experienced two episodes of quadriparesis within a short interval and responded dramatically to potassium replacement therapy.

Tumor necrosis factor-alpha and interleukin-1 beta levels in children with bacterial, tuberculous and aseptic meningitis.

Cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-1 beta in 78 children with nonbacterial, bacterial and tuberculous meningitis, and in 34 control subjects were analyzed in order to evaluate the involvement of these cytokines in the pathogenesis of acute bacterial meningitis and their discriminative value between different etiologies of meningitis. Tumor necrosis factor-alpha and interleukin-1 beta levels were significantly higher in bacterial and tuberculous meningitis than in aseptic meningitis and in control subjects (p < 0.0001). There was no difference in the levels of tumor necrosis factor-alpha and interleukin-1 beta between nonbacterial meningitis and control groups. The finding that both tumor necrosis factor-alpha and interleukin-1 beta are increased in the cerebrospinal fluid of patients with bacterial and tuberculous meningitis whereas normal levels of these two cytokines have been found in patients with nonbacterial meningitis signifies that these cytokines may be used to differentiate between bacterial and nonbacterial meningitis.

Ofloxacin versus co-trimoxazole in the treatment of typhoid fever in children.

Ofloxacin has been successfully used in the treatment of typhoid fever and Salmonella infectious of adults for many years. However, it has rarely been tried for the typhoid fever of children. In the present study, the therapeutic efficacy of ofloxacin in the treatment of typhoid fever in children was compared to that of co-trimoxazole. Out of 41 patients with bacteriologically documented typhoid fever, those with co-trimoxazole-resistant strains received 20 mg/kg ofloxacin twice daily for 10 days, and those with co-trimoxazole-susceptible bacteria were given 60 mg/kg co-trimoxazole twice daily for 10 days. Both groups were compared according to the clinical variables (apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms) and the time when cultures became negative. All patients in both groups were cured without relapse. Apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms were obtained in a significantly shorter time with ofloxacin than with co-trimoxazole (P < 0.05). The interval between onset of therapy and the time when cultures became negative was significantly shorter in the ofloxacin group than in the co-trimoxazole group (P = 0.005). Ofloxacin seems to be a good alternative in the treatment of typhoid fever caused by co-trimoxazole resistant salmonellae in children aged less than 16 years. It is well tolerated by the patients and it causes no side effects with short-term usage.

Intravenous immunoglobulin treatment in children with Guillain-Barré syndrome.

We have retrospectively reviewed the data of 75 consecutive children diagnosed with Guillain-Barré syndrome (GBS) and hospitalized in two centres. There were 51 children with GBS treated in Ankara, Turkey and 24 patients treated in Toronto, Canada. To evaluate the effect of intravenous immunoglobulin (IVIG) treatment, the patients were divided into three groups. All 24 Canadian patients received IVIG in a dose of 1 g/kg/day for 2 days. In the Ankara group 23 children received 0.4 g/kg/day for 5 days and the remaining 28 patients in that group received supportive treatment only. In all but two patients IVIG was started within the first 2 weeks of neuropathic symptoms. The patients' data, including mean functional grades, frequency of bulbar signs and autonomic dysfunction and age were similar in all three groups. Analysis of the short-term outcome demonstrated that the patients treated with IVIG had a significantly faster rate of recovery. Mean time-lapse until improvement of one functional grade was 17.4 days in the IVIG group from Toronto, and 20.8 days in the IVIG group and 62.4 days in the non-IVIG group of patients from Ankara. We conclude that IVIG has considerable efficacy in the treatment of children with GBS. Furthermore, we have also demonstrated a faster rate of recovery in patients who received a total dose of IVIG in 2 days as opposed to 5 days.

Antibiotic susceptibilities of Salmonella serogroups isolated from Turkish children.

This study is performed to show the serogroup distribution and in-vitro antibiotic susceptibilities of Salmonella species that cause either gastroenteritis with/without bacteremia or enteric fever at Hacettepe University Ihsan Dogramaci Children's Hospital. Of the 309 Salmonella strains evaluated, serogroup B was the most common isolate (56%) followed by serogroup D (33%). Antibiotic susceptibility tests using the disk diffusion technique revealed resistance rates of 43 percent for ampicillin, 41 percent for chloramphenicol, 29 percent for trimethoprim-sulfamethoxazole (SXT) and 32 percent for ceftriaxone among Salmonella serogroup B. The same rates were 10, eight, seven and zero percent for Salmonella serogroup D, and seven, 14, and zero percent for serogroup C, respectively. S.thypi strains susceptible to all antibiotics studied except tetracycline (33% resistant). No resistance was detected against the quinolones. The antibiotic resistance of Salmonella species isolated from children seems to be important, especially in serogroup B. Susceptibility tests should be considered in the antimicrobial therapy of Salmonella infections where indicated.

Antibiotic susceptibilities of enterococci isolated from Turkish children.

To evaluate the antibiotic resistance rates of enterococci isolated at Hacettepe Children's Hospital, in vitro antibiotic susceptibility tests were performed in 77 enterococci (32 hospital, 45 nonhospital strains) isolated from various clinical specimens in 1994. Microbroth dilution tests against ampicillin, vancomycin, gentamicin and streptomycin were performed according to the NCCLS standards. High-level resistance to aminoglycosides was investigated. Ampicillin resistance rates were 21.9 percent and 2.2 percent for hospital and nonhospital strains, respectively (p < 0.01). The same rates were 46.9 and 13.3 percent for gentamicin (p < 0.01), and 15.6 and 13.3 percent for streptomycin (p = 0.25). No resistance was detected against vancomycin. Six strains (7.8%) showed high-level resistance to both aminoglycosides studied. Special attention should be paid to enterococci isolated from hospitalized patients. Appropriate antibiotic use in serious infections can only be achieved by choosing an appropriate regimen according to antibiotic susceptibility tests. Periodic evaluation of the antibiotic susceptibility patterns of enterococci is necessary for the empirical treatment of infections due to these microorganisms.

Diagnosis of childhood tuberculosis by polymerase chain reaction.

The polymerase chain reaction (PCR) using oligonucleotides based on the repetitive sequence (IS6110) of Mycobacterium tuberculosis as a primer was evaluated for detection of M.tuberculosis in clinical samples. We tested 55 clinical specimens from patients suspected of having tuberculosis and 71 specimens from control subjects. PCR was more sensitive than culture (positivity rate was 14.5% and 36.3%, respectively, in suspected patients). This approach to the diagnosis of tuberculosis is a valid diagnostic alternative to classical procedures.

Microorganisms involved in acute bacterial meningitis in children and the role of Haemophilus influenzae.

Acute bacterial meningitis (ABM) is an important cause of mortality and neurological damage in children. Documentation of the etiological agents is very important both for the treatment of patients and for prophylactic approaches. H.influenzae, N.meningitidis and S.pneumoniae are the three major pathogens involved in ABM. In Turkey for many years H.influenzae has not been isolated in cerebrospinal fluid (CSF) specimens. In order to show the bacteria involved in ABM in our hospital and to see the role of H.influenzae, we investigated the CSF of 59 patients with bacterial meningitis using Gram and Wayson stains, culture and latex agglutination techniques. The agents were determined in 38 (64.4%) specimens by using culture positivity in 30 (50.8%), and latex or stain positivity in eight (13.6%) specimens. The microorganisms causing ABM included S.pneumoniae (25.6%), gram-negative enteric bacillI (17.9%), N.meningitis (12.8%), alpha hemolytic streptococci (10.3%), H.influenzae (10.3%), nonfermentative gram-negative bacillI (5.1%), candida spp. (5.1%), group B streptococci (2.6%), coagulase negative staphylococci (2.6%), S.aureus (2.6%) and pseudomonas spp. (5.1%). In this study it has been shown that H.influenzae can cause ABM in Turkish children. Multicentric studies from different parts of Turkey will be helpful in showing the real incidence in our country.