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G D Overturf

Publications and source records attributed to G D Overturf.

At least 19 recordsLinked to original sources

Infection with Sin Nombre hantavirus: clinical presentation and outcome in children and adolescents.

OBJECTIVE: Sin Nombre hantavirus (SNV) is the leading causative agent of hantavirus cardiopulmonary syndrome (HCPS) in the United States and Canada. Relatively few cases of HCPS have involved children. This report describes the clinical characteristics of a series of pediatric cases of SNV infection in the United States and Canada from 1993 through March 2000. METHODS: We analyzed clinical and laboratory data on 13 patients who were </=16 years old with SNV infection from 1993 through March 2000 identified from a database at the University of New Mexico. RESULTS: The patients ranged from 10 to 16 years of age, with a median of 14. Fifty-four percent were female. Fifty-four percent were Native American. The most common prodromal symptoms were fever, headache, and cough or dyspnea (100%); nausea or vomiting (90%); and myalgia (80%). The most common physical findings at admission were tachypnea (67%) and fever (56%); hypotension was seen in 33% of patients. On admission, all patients manifested thrombocytopenia (median platelet count: 67 000/mm(3)) and elevated lactate dehydrogenase (median level: 1243 IU/L), and >85% of patients had elevated levels of serum aspartate aminotransferase, alanine aminotransferase, and hypoalbuminemia. Leukocytosis and hemoconcentration were seen in less than one third of patients at admission. HCPS developed in 12 of the 13 patients (92%), and 4 of those 12 died (33% case-fatality ratio). The majority of HCPS patients (8 of 12 [67%]) were critically ill and required mechanical ventilation. Extracorporeal membrane oxygenation was used in 2 patients, 1 of whom survived. An elevated prothrombin time (>/=14 seconds) at admission was predictive of mortality. CONCLUSIONS: Infection with SNV in children and adolescents causes HCPS with a clinical course and mortality rate similar to that described in adults. We believe that early recognition of HCPS in children and adolescents and appropriate referral to tertiary care centers that are experienced with HCPS are important in reducing mortality.

Adolescent↗

American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis.

Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100,000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15 microg/mL) in >90% of infants after 3 doses given at 2, 4, and 6 months of age. After priming doses, significant booster responses (ie, immunologic memory) are apparent when additional doses are given at 12 to 15 months of age. In efficacy trials, infant immunization with Prevnar decreased invasive infections by >93% and consolidative pneumonia by 73%, and it was associated with a 7% decrease in otitis media and a 20% decrease in tympanostomy tube placement. Adverse events after the administration of Prevnar have been limited to areas of local swelling or erythema of 1 to 2 cm and some increase in the incidence of postimmunization fever when it is given with other childhood vaccines. Based on data in phase 3 efficacy and safety trials, the US Food and Drug Administration has provided an indication for the use of Prevnar in children younger than 24 months.

Antibiotic Prophylaxis↗

Infections and immunizations of children with sickle cell disease.

Children with SCD are prone to invasive infections caused by S. pneumoniae and H. influenzae. Osteomyelitis is caused most often by Salmonella species and less often by S. aureus. The chest syndrome and its associated microvascular disease carry a risk of prolonged and severe infections for Mycoplasma, Chlamydia, and probably other lower respiratory pathogens, particularly in the group of children with SCD prone to pain or microvascular sequestration, such as those with SC hemoglobinopathy. Despite three decades of investigation, the immunopathologic mechanisms leading to these increased risks is not completely clear. Bone infarction and microvascular disease probably play a part in the predisposition to osteomyelitis. Dysfunctional IgG and IgM antibody response, a lack of splenic clearance, defects in alternative pathway fixation of complement, and opsonophagocytic dysfunction play a role in the predisposition to invasive infection from polysaccharide-encapsulated organisms. Immunization with the conjugate Haemophilus vaccines has largely controlled infections caused by this pathogen. Early recognition of SCD through neonatal screening allows early and vigorous antibiotic management of febrile episodes in children with SCD and has perhaps provided the greatest benefit. Treatment of acute febrile episodes should include antibiotics active against regional strains of S. pneumoniae and H. influenzae, whereas treatment of febrile lower respiratory infections should include macrolide antibiotics that are active against Chlamydia and Mycoplasma, as well as pneumococci and Haemophilus. To date, no convincing evidence exists for the efficacy of pneumococcal polysaccharide vaccines in children with SCD, but preliminary data with the conjugate pneumococcal vaccines in normal children and those with SCD suggest that they may be as successful as Haemophilus vaccines in controlling this infection once they are available. Prophylaxis with daily penicillin administration is recommended and is well founded on clinical trials. However, problems with pneumococcal penicillin resistance and the association of failure with a lack of compliance to antibiotic regimens will dictate continued reexamination of this modality for the prevention of pneumococcal infections.

Adolescent↗

Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis, and vaccination.

The incidence of invasive infection due to Streptococcus pneumoniae is 6.9 infections per 100 patient-years among children with sickle cell anemia (SS genotype) who are less than 5 years of age; this rate is 30-100 times that which would be expected in a healthy population of this age. Splenic dysfunction is the major contributor to the increased risk. Postulated abnormalities of immunologic defense mechanisms, including synthesis of polyclonal IgG and IgM, the alternative complement pathway, opsonic activity, and T and B cell interaction, may also enhance risk. Preceding or concomitant viral infection is suspected of predisposing to pneumococcal infection, but no definitive data are available. The most prevalent pneumococcal serotypes causing disease in this setting include types 6, 14, 18, 19, and 23; these same serotypes are most frequently involved in "vaccine failure." Current evidence demonstrates only modest protective efficacy for contemporary pneumococcal vaccines in young patients with sickle cell anemia; thus alternative vaccines are required. Convincing evidence for a protective effect of antibiotic prophylaxis has been obtained in limited time trials. However, presently used prophylactic regimens pose problems related to compliance and provide imperfect protection; moreover, their optimal duration remains unknown.

Anemia, Sickle Cell↗

Antibiotic treatment of community acquired bacterial meningitis.

Community acquired meningitis is predominantly caused by three agents: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis Four physical properties of available drugs--molecular size, protein binding, lipid solubility and ionization--affect drug entry to the central nervous system (CNS). These factors, coupled with acute changes in blood-brain barriers and intrinsic bactericidal activity, have a bearing on the success of treatment with all agents. Third generation cephalosporins have largely supplanted older regimens due to their intrinsic qualities of greater bactericidal activity, optimal cerebrospinal fluid pharmacokinetics, and low toxicity. The pharmacological principles of treatment of CNS bacterial infections, pharmacology of available drugs, and current treatment recommendations are reviewed.

Anti-Bacterial Agents↗

Antibacterial activity of crotalid venoms against oral snake flora and other clinical bacteria.

Despite heavy oral and fang contamination of crotalid species with a wide variety of potentially pathogenic bacteria, crotalid envenomation is associated with a low incidence of bacterial infection. Minimal inhibitory and bactericidal concentrations of venoms from three crotalid species were determined against six aerobic and eight anaerobic reference and oral crotalid microorganisms. All anaerobic isolates were resistant to greater than 20,480 micrograms/ml, whereas variable activity (range, 5-20,480 micrograms/ml) was observed for aerobic strains. Further studies against other aerobic clinical isolates demonstrated that venom had the greatest activity (MIC, less than or equal to 80 micrograms/ml) against staphylococci, Pseudomonas aeruginosa, and Enterobacter, Citrobacter, Proteus, and Morganella species. Inhibitory activity was lost with prolonged incubation for many gram-negative species. Crotalid venoms are broadly active against aerobic gram-negative and -positive bacteria. This activity may play a role in the low incidence of infection after envenomation injuries.

Animals↗

Phage typing of Staphylococcus intermedius.

Staphylococcus intermedius, a coagulase-positive staphylococcal species, is a common canine pathogen and a rare human wound pathogen. A total of 145 strains of S. intermedius (ATCC 29663, 4 reference strains, 4 human isolates, 44 canine infection isolates, and 92 isolates from canine gingiva) were screened for lysogenic phage by a modified Fisk method. Nineteen phage preparations were prepared for preliminary typing experiments. Lytic activity was observed on 93 of 145 (64.1%) isolates, yielding 44 lytic patterns with individual strains susceptible to one or more phages. Five phages lysed only a single strain, but lytic patterns varied from 1 to 11 lytic phages per isolate. A distinct lytic pattern did not separate canine or human wound isolates from canine gingival isolates. All human wound isolates fell into the two most common canine gingival or wound patterns; the single human nasopharyngeal isolate was not lysed by any phage. Twenty-two of 44 (55%) canine wound isolates and 65 of 92 (71%) gingival isolates yielded lytic patterns. Lysogenic phages are common in S. intermedius. This preliminary study suggests that phage typing may be a useful tool in distinguishing epidemiologically related strains.

Animals↗

Cefuroxime treatment failure of nontypable Haemophilus influenzae meningitis associated with alteration of penicillin-binding proteins.

A 10-year-old boy presented with nuchal rigidity and cerebrospinal fluid (CSF) leukocytosis initially and again on day 6 of intravenous cefuroxime therapy (200 mg/kg/day). Both CSF specimens yielded nontypable beta-lactamase-negative Haemophilus influenzae that were susceptible by disk tests but relatively resistant to cefuroxime (MIC, 8- to 16-fold greater than that of control isolates). To define the mechanism of resistance, the cefuroxime resistance marker was transformed to a susceptible H. influenzae recipient; inactivation and permeability of beta-lactam substrate were tested and the penicillin-binding protein (PBP) profiles were examined. Inactivation of beta-lactam substrate was not detected and reduced permeability was not found. However, reduced beta-lactam binding to PBPs 4 and 5 was observed; 18- to 27-fold more penicillin and 2.5-to 4-fold more cefuroxime was required to saturate or block 50% of the binding sites of these PBPs, respectively. Thus, reduced affinity of PBPs 4 and 5 for beta-lactam substrate appears to be the mechanism of cefuroxime resistance in this strain. The reduced affinity of these targets appears to have contributed to the bacteriologic and clinical failure in this patient.

Ampicillin↗

Neonatal necrotizing enterocolitis associated with delta toxin-producing methicillin-resistant Staphylococcus aureus.

Delta toxin-producing coagulase-negative staphylococci previously have been associated with necrotizing enterocolitis in neonates. We identified three preterm infants (body weight, 845 +/- 59 g) infected with methicillin-resistant Staphylococcus aureus (MRSA) who had a similar clinical syndrome, characterized by pustular dermatitis, bacteremia and necrotizing enterocolitis accompanied by gastric residua, abdominal distention, hematochezia and pneumatosis intestinalis. MRSA was recovered from all three infants at infected skin sites, blood or venous catheters and from two of three infants in stool specimens. Two infants also had Staphylococcus epidermidis isolated from stool. All MRSA isolates had identical microbiologic profiles: four plasmids with identical molecular weights; coproduction of enterotoxins A and B; and the same antibiotic susceptibilities. Of one skin isolate, two blood isolates and two stool isolates of MRSA that were tested, all had characteristic delta toxin hemolytic activity. All culture supernatants of these isolates evaluated for delta toxin were positive by Western blot analysis. The two strains of S. epidermidis isolated from stool were negative for delta-like toxin by a standardized enzyme-linked immunoassay. The clustering of these cases, the similarity of the clinical syndrome, and the prior association of necrotizing enterocolitis with delta-like toxins produced by S. epidermidis, suggest that delta toxin-producing MRSA (or other S. aureus isolates) also may be etiologic agents in some cases of necrotizing enterocolitis in newborns.

Bacterial Toxins↗

Analysis of emergency department management of suspected bacterial meningitis.

Previous studies of emergency department management of bacterial meningitis have indicated that there are often long delays before initiation of antibiotics. The purpose of our study was to determine whether these delays were related to specific aspects of patient management. From 1981 through 1988, we retrospectively reviewed the medical records of 122 patients primarily evaluated in the ED and admitted for suspected bacterial meningitis at a university (55) and a community (67) hospital. The median time (interquartile range) from ED registration until initiation of antibiotics (time to antibiotics) was 3.0 hours (1.6 and 4.3 hours, respectively) (total range, 0.5 to 18 hours). The time to antibiotics was not significantly related to the time of ED registration. Ninety percent of the total time to antibiotics occurred after the initial physician encounter. Time to antibiotics was significantly (P less than .00005) longer for patients in whom computed tomography scan and/or laboratory analysis of cerebrospinal fluid preceded initiation of antibiotics compared with patients in whom antibiotic administration was not contingent on the results of these procedures (4.3 [3.2 and 6.0] versus 1.9 [1.2 and 3.4] hours, respectively). Also, time to antibiotics was significantly (P less than .00005) longer for patients in whom antibiotics were initiated on the ward as compared with in the ED (4.5 [3.5 and 6.8] versus 2.2 [1.4 and 3.5] hours, respectively). We conclude that long delays exist in the ED before initiation of antibiotics for cases of suspected bacterial meningitis, and that in general these delays appear to be physician generated and to a great extent potentially avoidable.

Adolescent↗

Staphylococcus intermedius: clinical presentation of a new human dog bite pathogen.

Staphylococcus intermedius is a Gram-positive, coagulase-positive coccus that can be distinguished from Staphylococcus aureus by routine microbiological testing. Whereas S intermedius is recognized as flora and pathogen of dogs, it has never been isolated from human infections. We hypothesized that S intermedius may cause human dog bite wound infections and that it has been previously misidentified as S aureus. Fourteen isolates from clinically infected dog bite wounds that were originally identified as S aureus were subjected to further testing; three (22%) were found to be S intermedius. The clinical and microbiological characteristics of these three S intermedius cases are described. All three patients were nonimmunocompromised persons seen within 24 hours for bites on the upper extremity. All patients developed cellulitis within one to three days. All S intermedius isolates were distinguished from S aureus by the lack of acetoin production and by the presence of beta-galactosidase activity. S intermedius was susceptible to a wide range of antibiotics; one isolate was resistant to penicillin. Two patients were treated with penicillin, one with amoxicillin-clavulanate, and all were clinically cured. These are the first three reported human infections involving S intermedius. Further study is necessary to define its clinical importance as a potential human pathogen.

Adult↗