The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: A retrospective study.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain. METHODS: The data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively. RESULTS: Records from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9-42.0) and 14.6 (5.4-40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively. CONCLUSION: The macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.

Effect of intravenous immunoglobulin for neonates with severe enteroviral infections with emphasis on the timing of administration.

BACKGROUND: The benefits of intravenous immunoglobulin (IVIG) therapy for severe neonatal enterovirus infections are still controversial. OBJECT: To evaluate whether timing of IVIG administration might affect clinical outcomes of neonates with severe enteroviral infections. STUDY DESIGNS: We retrospectively analyzed 67 neonates with culture-confirmed severe enteroviral infection, defined as hepatitis with coagulopathy and thrombocytopenia. Clinical features, outcomes and the usage of IVIG therapy were collected and analyzed. IVIG administered within 3 days of illness onset was classified as early IVIG therapy. RESULTS: Of the 67 cases, 38 (57%) were male, 27 (40%) were premature, 57 (85%) had disease onset within 7 days of life and all but 2 cases were caused by coxsackievirus B group. Ten infants (15%) had clinically evident myocarditis. 41 infants (61%) received IVIG therapy and 29 were early IVIG therapy. Fifteen infants (22%) eventually died, without IVIG therapy for 7 infants. The deceased had a significantly higher peak serum aspartate aminotransferase (AST) level than the survivors (3539 vs. 866 IU/L, p<0.01). The timing of IVIG therapy was highly correlated with the timing of peak AST level in patients with early IVIG therapy. Multiple logistic regression analysis showed that a higher nadir hemoglobin level (adjusted odds ratio 2.8, 95% confidence interval: 1.4-5.4), no concurrent myocarditis (42.6 [3.4-5289]) and early IVIG therapy (14.7 [1.3-163]) were independently associated with a favorable prognosis. CONCLUSIONS: In defined severe neonatal enterovirus infections, serum AST level correlated with the disease severity. Early IVIG therapy, if needed, may be beneficial for survival.

Effects of lactoferrin-containing formula in the prevention of enterovirus and rotavirus infection and impact on serum cytokine levels: a randomized trial.

BACKGROUND: Lactoferrin has been shown to exhibit anti-enterovirus 71 (EV71) and antirotavirus properties. This trial was conducted to determine whether a formula containing bovine lactoferrin (bLF) exerts a protective effect against EV71 or rotavirus infection among children from 2 to 6 years old. METHODS: A prospective, randomized, single blind clinical trial of an oral supplement containing bLF (daily dose approximately 70 to 85 mg) was carried out with healthy children in a day care center from March 2002 to June 2003. The incidence of enterovirus or rotavirus infection and the serum level of interferon- gamma (IFN-γ) and interleukin-10 (IL-10) were compared between children receiving and not receiving bLF. RESULTS: A total of 172 children, 96 in group A, which received bLF, and 76 in group B which did not receive bLF, completed the trial. During the study period, no EV71 was isolated and seroconversion of EV71 antibodies was noted in only one child. Fourteen episodes of presumptive enterovirus infection and 12 episodes of presumptive viral enteritis were detected. No significant differences were observed between groups in the incidence of presumptive enterovirus infection or viral enteritis or the number of laboratory confirmed enterovirus or rotavirus infections. No significant differences were observed in the serum levels of IFN-γ and IL-10 between groups either prior to or following the trial. In both groups, IFN-γ levels increased, but IL-10 was unchanged following the trial. CONCLUSION: An oral supplement of bLF at a dose of 70 mg/day did not show any benefits in the prevention of EV71 or rotavirus infection, or any impact on IFN-γ or IL-10 serum levels in healthy children in this trial.

Recognition roles of the carbohydrate glycotopes of human and bovine lactoferrins in lectin-N-glycan interactions.

BACKGROUND: Lactoferrin is an iron-binding protein belonging to the transferrin family. In addition to iron homeostasis, lactoferrin is also thought to have anti-microbial, anti-inflammatory, and anticancer activities. Previous studies showed that all lactoferrins are glycosylated in the human body, but the recognition roles of their carbohydrate glycotopes have not been well addressed. METHODS: The roles of human and bovine lactoferrins involved in lectin-N-glycan recognition processes were analyzed by enzyme-linked lectinosorbent assay with a panel of applied and microbial lectins. RESULTS AND CONCLUSIONS: Both native and asialo human/bovine lactoferrins reacted strongly with four Man-specific lectins - Concanavalia ensiformis agglutinin, Morniga M, Pisum sativum agglutinin, and Lens culinaris lectin. They also reacted well with PA-IIL, a LFuc>Man-specific lectin isolated from Pseudomonas aeruginosa. Both human and bovine lactoferrins also recognized a sialic acid specific lectin-Sambucus nigra agglutinin, but not their asialo products. Both native and asialo bovine lactoferrins, but not the human ones, exhibited strong binding with a GalNAc>Gal-specific lectin-Wisteria floribunda agglutinin. Human native lactoferrins and its asialo products bound well with four Gal>GalNAc-specific type-2 ribosome inactivating protein family lectins-ricin, abrin-a, Ricinus communis agglutinin 1, and Abrus precatorius agglutinin (APA), while the bovine ones reacted only with APA. GENERAL SIGNIFICANCE: This study provides essential knowledge regarding the different roles of bioactive sites of lactoferrins in lectin-N-glycan recognition processes.

Antimicrobial susceptibility testing of Bordetella pertussis in Taiwan prompted by a case of pertussis in a paediatric patient.

In Taiwan, pertussis is a notifiable disease with a low incidence in recent years, and antimicrobial susceptibility testing for the causative agent, Bordetella pertussis, has not been reported to date. In May 2007, the Centers for Disease Control, Taiwan, was informed of a 1-month-old pertussis patient who did not respond to erythromycin treatment. In this study, we report the result of antimicrobial susceptibility testing performed for the suspected erythromycin-resistant isolate, as well as for an additional 27 B. pertussis clinical isolates that represented almost all epidemiologically unrelated isolates obtained throughout Taiwan between 2003 and 2007. All isolates were fully susceptible to azithromycin, erythromycin, clarithromycin and trimethoprim/sulfamethoxazole (MIC < or =0.047 mug ml(-1)). This result demonstrates the general susceptibility of B. pertussis to antimicrobial agents in vitro in Taiwan.

Pneumococcal meningitis in Taiwanese children: emphasis on clinical outcomes and prognostic factors.

Pneumococcal meningitis causes high morbidity or mortality in childhood despite the progress in medicine. Children with pneumococcal meningitis were identified and retrospectively reviewed. Forty-nine children were eligible, with mortality in 24.5% of all and neurological sequelae in 40.5% of survivors. In the analysis of clinical profiles, ventilator support (p = 0.001), septic shock (p < 0.001), multiple organ failure (p < 0.001) and lower cerebrospinal fluid (CSF) leukocyte count (p = 0.001) were more frequently found in non-survivors. Besides, CSF protein (p = 0.006) was higher in survivors with neurological sequelae. Initial dexamethasone usage and disease severity did not affect the occurrence of neurological sequelae. Multivariate logistic regression analysis revealed that CSF leukocyte count or=330 g l(-1) (p = 0.022) were significantly risk factors associated with poor outcomes, and physicians should be cautious if such conditions occur.

Nontyphoidal Salmonella bacteremia in previously healthy children: analysis of 199 episodes.

BACKGROUND: Nontyphoidal Salmonella (NTS) bacteremia is not rare in otherwise healthy children in Taiwan. Few studies described the clinical manifestations and outcomes of NTS bacteremia in previously healthy children. METHODS: Children with blood culture positive for NTS treated at Chang Gung Children's Hospital between May 1996 and June 2003 were identified from the microbiology logbook. Patients who had underlying events or concomitant diseases were excluded. RESULTS: We evaluated 199 patients. One hundred and eighteen (59.3%) were male children and 184 (92.5%) were between 3 months and 5 years of age. Fever (97.0%) and diarrhea (79.9%) were the most common initial presentations. Leukocytosis (leukocyte >15,000/mm) and elevated serum C-reactive protein concentration (> or =10 mg/L) were present in 14.6% and 79.4% of the patients, respectively. Eighty-three percent of 184 patients with antibiotic treatment received a third- or fourth-generation cephalosporin as definitive antibiotic therapy. Focal suppurative infections were present in 5 children (2.5%) on initial evaluation, and included meningitis in 2 and osteomyelitis in 3. Neither metastatic complications nor clinically recurrent diseases were found during a follow-up period of at least 12 months after treatment. No fatalities occurred in this series. CONCLUSIONS: In healthy children, NTS bacteremia was relatively benign and extraintestinal focal suppurative infections were infrequently seen. Less than 10 days of appropriate antibiotic treatment is probably adequate for those without a suppurative focus of infection.

Viral load in blood is correlated with disease severity of neonatal coxsackievirus B3 infection: early diagnosis and predicting disease severity is possible in severe neonatal enterovirus infection.

We conducted a study during an outbreak of coxsackievirus B3 infection in 2005 and found that viral RNA could be detected in patients' blood specimens soon after the onset of fever, and the level of viral RNA was positively correlated with disease severity. Timely diagnosis is possible in severe neonatal enterovirus infection.

Coxsackievirus B3 in human milk.

Coxsackievirus B3 can cause severe neonatal disease with high mortality. We present the first report of detection of coxsackievirus B3 in the mothers' milk of 2 severely infected neonates by culture and reverse transcriptase-polymerase chain reaction. Reverse transcriptase-polymerase chain reaction is a rapid and sensitive tool to detect coxsackievirus B3 in breast milk within few hours. By 12 to 14 days after onset of symptoms, coxsackievirus B3 could not be detected in the breast milk of the symptomatic mothers.

Clinical observation of meningitis caused by penicillin-susceptible and -non-susceptible Streptococcus pneumoniae in Taiwanese children.

AIM: To compare differences between clinical features and outcome in bacterial meningitis caused by penicillin-susceptible Streptococcus pneumoniae (PSSP) with that caused by penicillin-non-susceptible Streptococcus pneumoniae (PNSP). METHODS: All patients <18 yrs hospitalised with pneumococcal meningitis between January 1984 and December 2002 at Chang Gung Children's Hospital, Taipei were reviewed retrospectively. RESULTS: There were 28 PNSP (63.6%) and 16 PSSP cases of meningitis eligible for the study. The incidence of PNSP meningitis increased significantly over the 8-yr period (p = 0.007). Age <4 yrs (78.6% vs 50%), a lower initial white blood count (mean 11.7 vs 19.9 x10(9)/L), admission to the intensive care unit (70.4% vs 50%) and mortality (28.6% vs 6.3%) were more common in the PNSP group. However, the only significant finding was a lower proportion of polymorphic neutrophils in the CSF of the PNSP meningitis group (p = 0.04). CONCLUSIONS: There was an increase in PNSP isolates from patients with meningitis over the 8-yr study period. No major differences were observed in clinical or laboratory features or outcome between the PSSP and PNSP groups.

Clinical responses of patients with Kawasaki disease to different brands of intravenous immunoglobulin.

OBJECTIVE: To determine whether different brands of intravenous immunoglobulin (IVIG) administered to children with Kawasaki disease (KD) result in different outcomes. STUDY DESIGN: We analyzed children with KD and divided them into 4 groups according to the brand of IVIG. A coronary artery abnormality (CAA) was defined as having a lumen diameter (inner border to inner border) of > or =3 mm in KD cases <5 years old and > or =4 mm in cases > or =5 years old, and giant aneurysm was defined as a lumen diameter > or =8 mm. Patients were considered nonresponsive to IVIG therapy if fever persisted longer than 2 days after completion of treatment and needed retreatment with IVIG. RESULTS: We collected 437 cases, 29 (6.6%) were nonresponsive, 17 (3.9%) had CAA at convalescence, and 3 (0.7%) had giant aneurysm, 2 of whom had development of myocardial infarcts. Patients receiving Brand C IVIG, prepared with beta-propiolactone, had higher rates (10%, 9/93, P = .01) of CAA at convalescence and nonresponsiveness (13%, 12/93, P = .001); giant aneurysm occurred in 3/93 (3%) receiving Brand C IVIG and in 0/344 who received the other 3 brands (P = .008). CONCLUSIONS: IVIG, prepared with beta-propiolactone, was most significantly associated with nonresponsiveness, CAA at convalescence, and giant aneurysm. Physicians should be cautious when using IVIG prepared with beta-propiolactone or enzyme digestion to treat KD.

Epstein-Barr virus-associated infectious mononucleosis and risk factor analysis for complications in hospitalized children.

The characteristics of Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM) in Chinese children are rarely reported. To evaluate the clinical presentations and risk factors for complications of EBV-associated IM in previously healthy children in Taiwan, hospitalized children with the diagnosis of IM due to EBV infection from January 1998 to December 2002 were enrolled. Patients had to fulfill the serologic criteria for the diagnosis of primary EBV infection [viral capsid antigen immunoglobulin M (IgM)-(+), viral capsid antigen IgG-(+), and anti-Epstein-Barr nuclear antigen (EBNA) antibody-(-) with exclusion of other concurrent infections or underlying diseases]. Ninety eight children were eligible, with 79% younger than 5 years old (mean, 4.0 +/- 2.3 years). The male-to-female ratio was 2:1. Nearly all patients suffered from fever (mean duration 10.3 +/- 6.0 days). Cough/rhinorrhea, tonsillopharyngitis, cervical lymphadenopathy and hepatosplenomegaly were found over half of the patients. Atypical lymphocytosis (mean, 12 +/- 13%) and elevated serum aspartate aminotransferase (AST; mean, 167 +/- 183 IU/L) and alanine aminotransferase (mean, 221 +/- 222 IU/L) were the most striking laboratory findings. Various complications, including hematologic, hepatobiliary, central nervous system, and obstructive airway problems occurred in about 20% of patients with significantly prolonged course of hospitalization. All patients recovered uneventfully under supportive and immunomodulating management. Female gender, no signs of tonsillopharyngitis, white blood cell count < or =10,000/mm3 and AST > or =150 IU/L were significant risk factors for the occurrence of complications. Clinicians should monitor such patients closely and give proper treatment to decrease possible morbidity or even mortality should complications occur.

Clinical and laboratory manifestations of Kikuchi's disease in children and differences between patients with and without prolonged fever.

BACKGROUND: Kikuchi's disease (KD) is characterized by cervical lymphadenopathy with or without fever. It has been recognized worldwide but seldom reported in pediatric patients. METHODS: From January 1985 through December 2001, 64 patients younger than 18 years of age with pathologic proof of KD were enrolled in this study. The clinical manifestations, laboratory data and outcomes were reviewed. RESULTS: There were 35 male patients and 29 female patients with age ranging from 2 to 18 years and a median age of 16. All patients had cervical lymphadenopathy except 1 who had generalized lymphadenopathy. Lymph nodes of 32 patients (50%) were painful or tender or both. Lymphadenopathy was unilateral in 52 patients (82.5%). Lymphadenopathy associated with fever was observed in 21 patients (32.8%). Other signs such as skin rash, hepatomegaly or body weight loss were less common. Twenty-six patients (40.6%) had leukopenia and 2 patients had leukocytosis. Nearly one-fourth of the patients had mild liver dysfunction. Virologic or immunologic studies were normal in most patients. Patients with prolonged fever were more likely to have leukopenia (P < 0.05). All patients recovered, but 1 developed systemic lupus erythematosus 5 years later, and the other had vasculitis syndrome 2 years later. CONCLUSIONS: The clinical presentation of KD in pediatric patients is similar to that of adults. KD is a benign, self-limiting disease; prolonged fever occurred only in 32.8% of pediatric patients in our cohort. Leukopenia was the only feature significantly associated with prolonged fever.

Vesicoureteral reflux in hospitalized children with urinary tract infection: the clinical value of pelvic ectasia on renal ultrasound, inflammatory responses and demographic data.

BACKGROUND: The aims of this study were to determine whether renal pelvis dilation on ultrasound was reliable in predicting vesicoureteral reflux (VUR) and to assess the relationship of other clinical information of VUR in children with urinary tract infection (UTI). METHODS: We retrospectively reviewed clinical data, renal echo, and voiding cystourethrogram (VCUG) results in hospitalized children with their first episode of UTI, aged from 1 month to 5 years, during a 1-year period. RESULTS: There were 114 children with 228 kidneys eligible for the study. Unilateral pelvis size greater than 8 mm had 2.4 (p = 0.049, 95% CI: 1.0-5.9) and 3.7 (p = 0.025, 95% CI: 1.2-11.3) times greater risk for VUR and severe reflux, respectively. The sensitivity in detecting severe reflux was 27.8%, and the specificity was 90.5%. The positive and negative predictive values in suggesting severe VUR were 20.0% and 93.6%, respectively. The sum of bilateral pelvis sizes greater than 16 mm had higher risk for VUR and severe reflux (4.1 and 4.6 times) and similar specificity and negative predictive value for severe reflux. Age, gender, C-reactive protein, leukocytosis, pyuria and acute pyelonephritis did not show significant relationships to the reflux. CONCLUSIONS: Unilateral pelvis size greater than 8 mm or the sum of the bilateral pelvis sizes greater than 16 mm was associated with VUR, especially severe VUR. The possibility of severe reflux was lower than 10% when the reverse criteria were applied. However, the dilation of the renal pelvis did not predict all VUR precisely. We concluded that VCUG should still be performed in hospitalized children with UTI.

Rotavirus gastroenteritis associated with afebrile convulsion in children: clinical analysis of 40 cases.

BACKGROUND: The purpose of this study was to evaluate the clinical manifestations and outcomes of hospitalized children with afebrile seizures following rotavirus gastroenteritis. METHODS: We conducted a retrospective study enrolling patients under 18 years old who were admitted to our hospital during a 10-year period with the diagnosis of rotavirus gastroenteritis. We identified and further analyzed patients who presented with afebrile seizures, without previous seizure disorders, electrolyte imbalances or hypoglycemia. The statistical methods used were the Chi-square test, the Kruskal-Wallis test and the Mann-Whitney test. RESULTS: Of 1937 patients, 40 patients (24 female and 16 male patients) met the inclusion criteria. The incidence of afebrile seizures following rotavirus gastroenteritis was 2.06%. The age of the patients ranged from 6 months old to 6 years old (mean, 1.9 years). The highest incidence of afebrile seizures was 4.67% in children 1 to 2 years of age (p < 0.001). Twenty-seven patients (67.5%) had two or more seizures, which usually were in clusters within a 24-hour period. No status epilepticus was observed. More than half of the patients (52.5%) suffered from seizures on the third day of diarrhea. Only five of 35 patients showed abnormal electroencephalogram (EEG) findings, which reverted to normal in four of the patients during the follow-up period. Most patients did not require long-term anticonvulsant treatment. During the follow-up period, all patients displayed normal psychomotor development without the recurrence of seizures, except in one patient who had a febrile convulsion. CONCLUSION: We found that the course of afebrile seizures following rotavirus gastroenteritis was benign with satisfactory outcomes.