Use of real-time semiquantitative PCR data in management of a neonatal intensive care unit adenovirus outbreak.

OBJECTIVE: To describe an adenovirus outbreak in a neonatal intensive care unit (NICU), including the use of qualitative and semiquantitative real-time polymerase chain reaction (qPCR) data to inform the outbreak response. DESIGN: Mixed prospective and retrospective observational study. SETTING: A level IV NICU in the southeastern United States.PatientsTwo adenovirus cases were identified in a NICU. Screening of all inpatients with qPCR on nasopharyngeal specimens revealed 11 additional cases.InterventionsOutbreak response procedures, including enhanced infection control policies, were instituted. Serial qPCR studies were used to screen for new infections among exposed infants and to monitor viral clearance among cases. Changes to retinopathy of prematurity (ROP) exam procedures were made after an association was noted in those patients. At the end of the outbreak, a retrospective review allowed for comparison of clinical factors between the infected and uninfected groups. RESULTS: There were no new cases among patients after outbreak identification. One adenovirus-infected patient died; the others recovered their clinical baselines. The ROP exams were associated with an increased risk of infection (odds ratio [OR], 84.6; 95% confidence interval [CI], 4.5-1,601). The duration of the outbreak response was 33 days, and the previously described second wave of cases after the end of the outbreak did not occur. Revisions to infection control policies remained in effect following the outbreak. CONCLUSIONS: Retinopathy of prematurity exams are potential mechanisms of adenovirus transmission, and autoclaved or single-use instruments should be used to minimize this risk. Real-time molecular diagnostic and quantification data guided outbreak response procedures, which rapidly contained and fully terminated a NICU adenovirus outbreak.

Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children.

OBJECTIVES: To describe the clinical characteristics and course of children with laboratory-diagnosed Rocky Mountain spotted fever (RMSF) and to identify clinical findings independently associated with adverse outcomes of death or discharge with neurologic deficits. STUDY DESIGN: Retrospective chart review of 92 patients at six institutions in the southeastern and southcentral United States from 1990 to 2002. Statistical analyses used descriptive statistics and multiple logistic regression. RESULTS: Children with RMSF presented to study institutions after a median of 6 days of symptoms, which most commonly included fever (98%), rash (97%), nausea and/or vomiting (73%), and headache (61%); no other symptom or sign was present in >50% of children. Only 49% reported antecedent tick bites. Platelet counts were <150,000/mm3 in 59% of children, and serum sodium concentrations were <135 mEq/dL in 52%. Although 86% sought medical care before admission, only 4 patients received anti-rickettsial therapy during this time. Three patients died, and 13 survivors had neurologic deficits at discharge. Coma and need for inotropic support and intravenous fluid boluses were independently associated with adverse outcomes. CONCLUSIONS: Children with RMSF generally present with fever and rash. Delays in diagnosis and initiation of appropriate therapy are unacceptably common. Prognosis is guarded in those with hemodynamic instability or neurologic compromise at initiation of therapy.

Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals.

Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy. The greatest challenge to clinicians is the difficult diagnostic dilemma posed by these infections early in their clinical course, when antibiotic therapy is most effective. Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses Branch, in consultation with 11 clinical and academic specialists of Rocky Mountain spotted fever, human granulocytotropic anaplasmosis, and human monocytotropic ehrlichiosis, developed guidelines to address the need for a consolidated source for the diagnosis and management of TBRD. The preparers focused on the practical aspects of epidemiology, clinical assessment, treatment, and laboratory diagnosis of TBRD. This report will assist clinicians and other health-care and public health professionals to 1) recognize epidemiologic features and clinical manifestations of TBRD, 2) develop a differential diagnosis that includes and ranks TBRD, 3) understand that the recommendations for doxycycline are the treatment of choice for both adults and children, 4) understand that early empiric antibiotic therapy can prevent severe morbidity and death, and 5) report suspect or confirmed cases of TBRD to local public health authorities to assist them with control measures and public health education efforts.

Human monocytic ehrlichiosis in children.

BACKGROUND: Human monocytic ehrlichiosis (HME) is a tick-borne illness caused by Ehrlichia chaffeensis. Data about disease in children have been largely derived from case reports or small case series. METHODS: A retrospective review of all medical and laboratory records from 6 sites located in the "tick belt" of the Southeastern United States was carried out. Demographic, history and laboratory data were abstracted from the identified medical records of patients. Bivariate statistical comparisons were performed using Fisher exact test or Wilcoxon rank sum tests. RESULTS: Common clinical signs and symptoms of patients with HME (n = 32) included fever (100%), headache (69%), myalgia (69%), rash (66%), nausea/vomiting (56%), altered mental status (50%) and lymphadenopathy (47%). Only 48% had a complaint of fever, headache and rash. Common laboratory abnormalities included thrombocytopenia (94%), elevated aspartate aminotransferase (90%), elevated alanine aminotransferase (74%), hypoalbuminemia (65%), lymphopenia (57%), leukopenia (56%) and hyponatremia (55%). The median number of days of illness before the initiation of antirickettsial therapy was 6. Patients who received sulfonamides before starting doxycycline therapy developed a rash, were admitted to the hospital, and started doxycycline at a later date. Twenty-two percent of patients were admitted to the intensive care unit with 12.5% of patients requiring ventilatory and blood pressure support. CONCLUSIONS: Although HME has been recognized among children for almost 20 years, there is only a limited knowledge about its clinical course. Even among physicians practicing in endemic regions, few cases are diagnosed each year. More work is needed to understand the true burden of disease and the natural history among asymptomatically and symptomatically infected children.

Group B streptococcal ventriculitis: a report of three cases and literature review.

This report presents three cases of neonatal group B streptococcal ventriculitis and assesses seven others identified by a literature review. In contrast to the well described acute manifestations of group B streptococcal meningitis, disease onset tended to be insidious with four of seven cases presenting over a period of 1 to 6 weeks and six cases presenting with nonspecific signs and symptoms without fever. Persistent protein content elevation and low glucose level in the cerebrospinal fluid was observed, indicating chronic inflammation. All patients developed obstructive hydrocephalus requiring ventriculoperitoneal shunt placement. One child died, and six of nine survivors were left with significant neurologic deficits. Physicians should be aware of this indolent but serious manifestation of group B streptococcal infection.

Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies.

Ticks can transmit bacterial, protozoal, and viral infections to humans. Specific therapy is available for several of these infections. Doxycycline is the antimicrobial treatment of choice for all patients, regardless of age, with Rocky Mountain spotted fever, human monocytic ehrlichiosis, or human granulocytic ehrlichiosis. Chloramphenicol has been used to treat these infections in children but is demonstrably inferior to doxycycline. In patients with Mediterranean spotted fever, doxycycline, chloramphenicol, and newer macrolides all appear to be effective therapies. Therapy of Lyme disease depends on the age of the child and stage of the disease. For early localized disease, amoxicillin (for those aged <8 years) or doxycycline (for those aged >/=8 years) is effective. Doxycycline, penicillin V (phenoxymethylpenicillin) or penicillin G (benzylpenicillin) preparations, and erythromycin are all effective treatments for tick-borne relapsing fever. Hospitalized patients with tularemia should receive gentamicin or streptomycin. Doxycycline and ciprofloxacin have each been investigated for the treatment of tularemia in outpatients; however, these agents do not yet have established roles in the treatment of this disease in children. Combination therapy with clindamycin and quinine is preferred for children with babesiosis; the combination of azithromycin and atovaquone also appears promising. Ribavirin has been recently shown to markedly improve survival in patients with Crimean-Congo hemorrhagic fever. The role of antiviral therapy in the treatment of other tick-borne viral infections, including other hemorrhagic fevers and tick-borne encephalitis, is not yet defined.

Methicillin-resistant Staphylococcus aureus as a pathogen in deep neck abscesses: a pediatric case series.

OBJECTIVES: Pediatric deep neck space abscesses are frequently treated by the otolaryngologist. We report four children with deep neck abscesses caused by methicillin-resistant Staphylococcus aureus (MRSA), including the first described case of descending mediastinitis caused by MRSA in a child. METHODS: Records from March 2001 to April 2002 were reviewed. RESULTS: Four patients presented with neck swelling, and three of these also had leukocytosis. All abscess cultures were positive for MRSA. Abscess drainage with antibiotic therapy successfully treated three cases without complication. The fourth case developed descending mediastinitis but survived after additional surgical treatment and prolonged antibiotic therapy. CONCLUSIONS: MRSA should be considered as a potential pathogen in deep neck space abscesses. A high index of suspicion is needed as well as aggressive treatment including incision and drainage along with culture-directed medical therapy. Surgical drainage may be the most important aspect of therapy.

Tick-borne diseases of the USA: Ten things clinicians should know.

This article highlights critical aspects of the epidemiology, diagnosis, and management of tick-borne infections in children. Principles that apply broadly across the continental United States are emphasized, rather than details of each disease. Tick-borne infections are often confused with other, more common childhood illnesses, in part because of their nonspecific initial clinical findings and because patients are usually unaware of their preceding tick exposures. This is a problem, because delays in starting appropriate antibiotic therapy increase the likelihood of adverse outcomes from these infections, especially Rocky Mountain spotted fever (RMSF). For patients in whom RMSF is a reasonable diagnostic consideration, therapy should be started presumptively, without awaiting the results of confirmatory diagnostic tests. For both adults and children, doxycycline is the drug of choice for RMSF and other American rickettsial infections. Concerns over the potential toxicity of doxycycline in young children are unfounded. Similarly groundless is the belief in "chronic Lyme disease" as an explanation for persistent nonspecific complaints after completing antibiotic therapy for Lyme disease. Prevention of tick-borne infections rests on avoidance of tick-bites and prompt removal of attached ticks. When used appropriately, insect repellents containing DEET are safe and effective for preventing tick exposures.

Recognition of and Prompt Treatment for Tick-Borne Infections in Children.

Tick-borne infections create diagnostic challenges because they tend to present with nonspecific findings. Because clinicians often fail to recognize tick-borne illnesses in early stages, therapy is frequently delayed or omitted. This is especially problematic for rickettsial infections (Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis), because the risk of long-term morbidity and mortality increases with delayed treatment. We emphasize the need for clinicians to maintain a high index of suspicion for tick-borne infections; to diagnose these illnesses presumptively, without waiting for confirmatory laboratory test results; and to promptly start therapy with doxycycline, even in young children, when rickettsial infections are suspected.

Pneumonitis associated with Ureaplasma urealyticum in children with cancer.

We describe 3 pediatric patients with cancer who had clinical and radiographic evidence of pneumonitis and for whom cultures of bronchoalveolar lavage fluid specimens yielded Ureaplasma urealyticum. Two of the patients died; for the surviving patient, clinical improvement coincided temporally with administration of erythromycin. Immunocompromised patients with pneumonitis of unclear etiology should have respiratory secretions cultured for mycoplasmas and should receive empiric therapy that includes a macrolide antibiotic.

Decreasing beta-lactam resistance in Pneumococci from the Memphis region: analysis of 2,152 isolates From 1996 to 2001.

STUDY OBJECTIVES: The Memphis region historically has had high pneumococcal antibiotic resistance rates. In recent years, we have seen a significant shift in antibiotic use away from beta-lactams toward the newer quinolones and macrolides. We hypothesized that these changes would cause a shift in pneumococcal antibiotic resistance patterns. DESIGN: Retrospective cohort study. SETTING: A large private hospital system. PATIENTS AND METHODS: We analyzed the antibiotic susceptibility patterns of 2,152 pneumococcal isolates obtained in the Memphis area from 1996 to 2001. Isolates were categorized as invasive or noninvasive and antibiotic resistance was classified according to the 2000 guidelines of the National Committee for Clinical Laboratory Standards. RESULTS: Over the study period, the proportion of penicillin-susceptible noninvasive pneumococcal isolates taken from children increased from 22 to 44% (p = 0.0004 [for trend across the 6-year period]). In noninvasive isolates taken from adults, penicillin susceptibility increased from 22 to 55% (p = 0.002), with a trend toward increasing sensitivity to cefotaxime (p = 0.02) in noninvasive isolates over the same period. The proportion of isolates with high-level penicillin resistance (ie, minimum inhibitory concentration, > or = 4 microg/mL) also decreased between 1996 and 2001 (p = 0.003). Clindamycin resistance in adult noninvasive isolates also declined (p = 0.002). The only adverse trend observed over this period was an increase in erythromycin resistance in noninvasive isolates from adults (p = 0.01). Resistance rates were significantly higher in children than in adults and were higher in noninvasive isolates than in invasive isolates. CONCLUSIONS: The stabilization of beta-lactam resistance rates in our region suggests that a continuous increase in pneumococcal resistance to antibiotics is not inevitable and may be avoidable.

Incidence and etiologies of complicated parapneumonic effusions in children, 1996 to 2001.

BACKGROUND: The incidence and causative organisms associated with complicated parapneumonic effusions in children with community-acquired pneumonia are likely to have changed during the past several years. METHODS: Data regarding clinical and laboratory features were abstracted retrospectively from medical records of 76 subjects with complicated parapneumonic effusions at a tertiary children's hospital from 1996 through 2001. Incidence rates per 10 000 hospital discharges and per 1000 patients with nonviral pneumonia were calculated. RESULTS: Etiologic organisms were Streptococcus pneumoniae (31 subjects), Staphylococcus aureus (7), Streptococcus pyogenes (5), Abiotrophia sp. (1) and no culture-confirmed agent (32). The annual incidence of complicated parapneumonic effusions per 10 000 discharges progressively increased from 4.5 in 1996 to 25.0 in 1999 (P = 0.0001), then declined to 10.1 in 2001 (P = 0.03). Similarly the incidence per 1000 cases of nonviral pneumonia increased from 2.9 in 1996 to 11.0 in 1999 (P = 0.003) and then declined to 4.8 in 2001 (P = 0.053). Whereas S. pneumoniae was the leading confirmed etiology in each year, the proportion of cases caused by Staphylococcus aureus increased from 6% in 1996 to 2000 (all of which were methicillin-susceptible) to 30% in 2001 (all methicillin-resistant; P = 0.04). CONCLUSIONS: The incidence of complicated parapneumonic effusions in children with community-acquired pneumonia increased from 1996 to 1999 and then declined concomitant with the introduction of the pneumococcal conjugate vaccine. Although cases caused by S. pneumoniae have decreased, community onset methicillin-resistant Staphylococcus aureus has emerged as a cause of pneumonia with complicated effusions in children.

Outbreak of aseptic meningitis associated with echovirus 13.

BACKGROUND: Before 2001, echovirus 13 accounted for only 65 of approximately 45,000 reported enteroviral isolates in the United States. During spring 2001, several outbreaks of echovirus 13 meningitis occurred, primarily affecting children. We investigated a large outbreak in Shelby County, TN, to determine the characteristics and clinical manifestations of echovirus 13 meningitis. METHODS: We identified cases of aseptic meningitis at a children's hospital from April through August 2001 by reviewing discharge records. For patients with laboratory-confirmed echovirus 13 meningitis, we reviewed charts and interviewed parents. RESULTS: We identified 303 hospitalizations caused by aseptic meningitis at the children's hospital from April through August. Hospitalizations peaked in May. Twenty-six percent of hospitalized patients were infants age <4 months; 63% were male. Hospitalization rates were 3 times greater among black children than among white children (140 vs. 47 per 100,000). Echovirus 13 was isolated from specimens from 37 (80%) of 46 patients with positive viral cultures. Of those with laboratory-confirmed echovirus 13, 35 (95%) had fever, 26 (70%) had vomiting, 20 (54%) had headache, 16 (43%) had stiff neck and 16 (43%) had irritability. No sequelae or deaths were identified. CONCLUSIONS: Echovirus 13 emerged as a predominant strain of enterovirus associated with aseptic meningitis in the United States in 2001. In this outbreak echovirus 13 meningitis appeared to be clinically indistinguishable from aseptic meningitis caused by other enteroviruses.

Emergence of community-associated methicillin-resistant Staphylococcus aureus at a Memphis, Tennessee Children's Hospital.

BACKGROUND: An epidemiologic investigation was performed because of a perceived increase in infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) among children in the greater Memphis area. METHODS: We reviewed medical records of 289 children evaluated from January 2000 to June 2002 at a children's hospital. Clinical criteria were applied to classify MRSA isolates as community-associated (n=51) or health care-associated (n=138). The relatedness of 33 archived S. aureus isolates was evaluated using pulsed field gel electrophoresis (PFGE) of Sma I-digested genomic DNA; a common pulsed field type was defined as > or = 80 % similarity based on Dice coefficients. PFGE profiles were compared with those in a national database of MRSA isolates. RESULTS: During the first 18 study months, 46 of 122 MRSA isolates (38%) were community-associated; this proportion increased to 106 of 167 isolates (63%) during the last 12 study months (P <.0001). Community-associated isolates were recovered from normally sterile sites as frequently as were health care-associated isolates (16% versus 13%). PFGE revealed that 15 of 16 community-associated isolates shared a common pulsed field type (USA300) observed in community-associated MRSA infections elsewhere in the United States and characterized by staphylococcal cassette chromosome mec type IV, clindamycin susceptibility and erythromycin resistance mediated by an msr A-encoded macrolide efflux pump. CONCLUSIONS: Community-associated MRSA has emerged as a potentially invasive pathogen among children in the greater Memphis area, and this phenomenon is not explained by spread of nosocomial strains into the community.

Ehrlichia chaffeensis seroprevalence among children in the southeast and south-central regions of the United States.

BACKGROUND: The reported annual incidence of human monocytic ehrlichiosis, which is due to infection with Ehrlichia chaffeensis, is as high as 5.5 per million in some states, but serosurveys suggest much higher infection rates in some populations. OBJECTIVE: To estimate the prevalence of E chaffeensis infection among children aged 1 to 17 years living in the southeast and south-central United States. DESIGN: Cross-sectional serosurvey. SETTING: Seven academic pediatric medical centers in the southeastern and south-central United States. PATIENTS: Nineteen hundred ninety-nine children (approximately 300 at each center) having their blood drawn for any reason. MAIN OUTCOME MEASURE: The presence of antibody at 2 different cutoff titers to E chaffeensis, as detected by indirect immunofluorescence assay. RESULTS: Overall, 250 children (13%) had E chaffeensis antibody titers of 1:80 or higher and 61 (3%) had titers of 1:160 or higher. Age-adjusted seroprevalence rates varied widely between sites. At 1:80 or higher, the highest rate was in Winston-Salem, NC (22%), and the lowest was in Louisville, Ky (2%). At 1:160 or higher, the highest rate was in Kansas City, Mo (9%), and the lowest was in Oklahoma City, Okla (<1%). In univariate analyses, no associations were found between seroprevalence at either cutoff value and sex, race, source of specimen, or residence demographics. However, age was a significant predictor of seroprevalence at both cutoff values. In multiple logistic regression analysis, study site and age remained strong predictors of seroprevalence, but living in a nonurban ZIP code was not significantly related. CONCLUSION: Infection with E chaffeensis, or related ehrlichiae, may be more common in children than previously recognized.

Antibodies reactive to Rickettsia rickettsii among children living in the southeast and south central regions of the United States.

BACKGROUND: The reported annual incidence of Rocky Mountain spotted fever in the United States is 2.2 per million, but studies have suggested that human infection with Rickettsia rickettsii may be more common. This study estimated the prevalence of antibodies reactive to R rickettsii among children living in the southeastern and south central United States. STUDY DESIGN: Approximately 300 specimens were obtained from children at each of 7 pediatric referral centers (N = 1999). Serum was tested for R rickettsii antibodies by means of indirect immunofluorescence antibody assay. Three different cutoff titers (>or=64, >or=128, and >or=256) represented increasing levels of stringency to define positive specimens. RESULTS: Overall, 12.0% of children had R rickettsii antibody titers of at least 64; 7.3%, at least 128; and 4.3%, at least 256. Strong relationships were seen between increasing age and seroprevalence at each cutoff titer. Remarkably, 6.4% of children aged 13 to 17 years had titers of at least 256. Age-adjusted seroprevalence rates at titers of at least 64 varied from 21.9% in Little Rock, Ark, to 3.5% in Louisville, Ky. At titers of at least 256, seroprevalence ranged from 7.7% in Nashville, Tenn, to 1.8% in Winston-Salem, NC. Only site and age group were strong predictors of seropositivity; a weak association was seen with nonurban residence. CONCLUSIONS: To our knowledge, this is the largest serosurvey of rickettsial infection in children in the United States. Within the limitations of the immunofluorescence antibody assay, these data suggest that infections with R rickettsii or antigenically related spotted-fever group rickettsiae may be common and subclinical. The results also have implications for the interpretation of single immunofluorescence antibody assay titers in children with suspected Rocky Mountain spotted fever.

Managing Rocky Mountain spotted fever.

Rocky Mountain spotted fever is caused by the tick-borne bacterium Rickettsia rickettsii. Symptoms range from moderate illness to severe illness, including cardiovascular compromise, coma and death. The disease is prevalent in most of the USA, especially during warmer months. The trademark presentation is fever and rash with a history of tick bite, although tick exposure is unappreciated in over a third of cases. Other signature symptoms include headache and abdominal pain. The antibiotic therapy of choice for R. rickettsii infection is doxycycline. Preventive measures for Rocky Mountain spotted fever and other tick-borne diseases include: wearing long-sleeved, light colored clothing; checking for tick attachment and removing attached ticks promptly; applying topical insect repellent; and treating clothing with permethrin.

Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus.

INTRODUCTION: An increase in the incidence and severity of acute osteoarticular infections in children was perceived after the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in our community. This study was performed to describe changes in the epidemiology and clinical features of acute osteoarticular infections. METHODS: The records of patients discharged from Le Bonheur Children's Medical Center with a diagnosis of acute osteoarticular infection between 2000 and 2004 were reviewed. Data regarding signs and symptoms, diagnostic testing, therapeutics, surgery, and hospital course were collected. RESULTS: There were 158 cases of acute osteoarticular infection. The incidence increased from 2.6 to 6.0 per 1000 admissions between 2000 and 2004. The proportion of infections caused by methicillin-susceptible S. aureus (MSSA) remained constant (10%-13%) and that caused by MRSA rose from 4% to 40%. There was no difference between MRSA and MSSA patients in the duration of fever or pain before diagnosis. Seventy-one percent of patients with MRSA had subperiosteal abscesses compared with 38% with MSSA (P = 0.02). Ninety-one percent of MRSA patients required a surgical procedure compared with 62% of MSSA patients (P < 0.001). Median hospital stay was 7 days for MSSA patients and 10 days for MRSA patients (P = 0.0001). Three patients developed chronic osteomyelitis, 2 with MRSA. There was no association between a delay in institution of appropriate antibiotic therapy and presence of subperiosteal abscess (P = 0.8). CONCLUSIONS: There has been an increase in the incidence and severity of acute osteoarticular infections in Memphis. Patients with community-associated MRSA infections are at higher risk of subperiosteal abscess requiring surgical intervention.