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Sheldon L Kaplan

Publications and source records attributed to Sheldon L Kaplan.

At least 37 records · Page 2Linked to original sources
PubMed2005

Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents.

Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m2/day or 70 mg/m2/day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC(0-24)) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m2/day (maximum, 70 mg/day), the AUC(0-24) following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC(0-24) and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m2 daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at 1 mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m2/day provides a comparable exposure to that of adult patients treated with 50 mg/day.

Adolescent↗
PubMed2005

Severe Staphylococcal sepsis in adolescents in the era of community-acquired methicillin-resistant Staphylococcus aureus.

OBJECTIVE: More than 70% of the community-acquired (CA) staphylococcal infections treated at Texas Children's Hospital are caused by methicillin-resistant Staphylococcus aureus (MRSA). Since September 2002, an increase in the number of severely ill patients with S aureus infections has occurred. This study provides a clinical description of severely ill adolescent patients and an analysis of their isolates using molecular methods. METHODS: We identified adolescent patients meeting criteria for severe sepsis requiring admission to the PICU. Patient records were reviewed, and isolates were obtained for susceptibility testing and DNA extraction. Isolates were tested for the presence of virulence genes (cna, tst, lukS-PV, and lukF-PV) and enterotoxin genes (sea, seb, sec, sed, seh, and sej) by polymerase chain reaction. Genomic fingerprints were determined by repetitive-element polymorphism polymerase chain reaction and pulse-field gel electrophoresis. SCCmec cassette type was determined. RESULTS: Fourteen adolescents with severe CA S aureus infections were identified between August 2002 and January 2004. All were admitted to the PICU with sepsis and coagulopathy. Twelve patients had CA-MRSA infections; 2 had CA methicillin-susceptible Staphylococcus aureus (MSSA) infections. The mean age was 12.9 years (range: 10-15 years). Thirteen patients had pulmonary involvement and/or bone and joint infection; 10 patients had > or =2 bones or joints infected (range: 2-10); 4 patients developed vascular complications (deep venous thrombosis); and 3 patients died. All isolates were identical or closely related to the previously reported predominant clone in Houston, Texas (multilocus sequence type 8, USA300), and carried lukS-PV and lukF-PV genes as well as the SCCmec type IVa cassette (12 MRSA isolates) but did not contain cna or tst. Only 1 strain carried enterotoxin genes (sed and sej). CONCLUSIONS: Severe staphylococcal infections in previously healthy adolescents without predisposing risk factors have presented more frequently at Texas Children's Hospital since September 2002. CA MRSA and clonally related CA MSSA characterized as USA300 and sequence type 8 have been isolated from these patients.

Adolescent↗
PubMed2004

Pneumococcal endocarditis in children.

Endocarditis due to Streptococcus pneumoniae is unusual in children, accounting for 3%-7% of all cases of childhood endocarditis. The US Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified patients with invasive disease at 8 children's hospitals. During the period of 1 September 1993 through 28 February 2003, a total of 11 children with pneumococcal endocarditis were seen. Seven (64%) were 3-36 months old; 8 (73%) were boys. Ten (91%) had preexisting structural heart disease; 5 had undergone previous heart surgery. Concomitant sites of infection were noted in 6 patients (55%), including 3 patients with meningitis. One patient (9%) died during hospitalization, and 5 others (45%) experienced serious complications. Only 2 patients remained hospitalized for their entire course of parenteral antibiotic therapy. Eight of 10 pneumococcal isolates tested were vaccine or vaccine-related serotypes included in the currently licensed 7-valent conjugated pneumococcal vaccine. Pneumococcal endocarditis in children is unusual but often has serious complications.

Adolescent↗
PubMed2004

Cell adhesion molecules and cytokines in middle ear effusions in children with or without recent acute otitis media.

OBJECTIVES: We sought to compare the levels of cytokines and cell adhesion molecules in middle ear effusions (MEEs) of children with (group 1) or without (group 2) acute otitis media (AOM) within 3 months of obtaining MEE and to correlate these levels with hearing loss. DESIGN AND SUBJECTS: MEE were collected from children (49 and 51 children composed groups 1 and 2, respectively) with otitis media with effusion (OME) undergoing tube placement who had an audiogram performed preoperatively. MEE was assessed as serous or mucoid. Cytokines and cell adhesion molecules were measured by enzyme-linked immunosorbent assay. Data were analyzed with the Student t test, chi(2) test, and the Pearson correlation test. RESULTS: Concentrations of interleukin (IL)-1, IL-6, and vascular cell adhesion molecules (VCAM) were greater in the MEE of the children in group 1 compared with those of group 2 children. (P < 0.001 for IL-1 and IL-6; P < 0.05 for VCAM). The concentrations of IL-1, IL-6, VCAM, and E-selectin were greater in serous than in mucoid MEE. (P < 0.05). Concentrations of IL-6 correlated with the concentrations of the other 2 cytokines and the 3 cell adhesion molecules. Only concentrations of IL-6 in MEE correlated with the degree of hearing loss (P < 0.002). CONCLUSIONS: The inflammatory response leading to OME involves multiple cytokines regardless of an AOM episode in the 3 months before obtaining MEE. IL-6 is an important cytokine in the pathogenesis of OME.

Cell Adhesion Molecules↗
PubMed2004

Azithromycin compared with beta-lactam antibiotic treatment failures in pneumococcal infections of children.

OBJECTIVE: To determine whether treatment failures occurred more commonly with azithromycin than with beta-lactam antibiotics in children who developed invasive pneumococcal disease within 30 days of receiving prior antimicrobial therapy. METHODS: Retrospective review of medical records of children evaluated at Texas Children's Hospital between 1996 and 2002 who had received antimicrobials (azithromycin or a beta-lactam antibiotic) and developed invasive pneumococcal disease within 30 days. Treatment failure was defined as invasive pneumococcal infection that occurred while taking antimicrobials or within 3 days of stopping azithromycin treatment or 1 day of stopping beta-lactam treatment. Penicillin and azithromycin susceptibilities were determined and categorized according to National Committee for Clinical Laboratory Standards guidelines. RESULTS: We identified 21 and 33 children with similar demographic features who had developed invasive pneumococcal disease within 1 month of receiving azithromycin or a beta-lactam antibiotic, respectively. Eleven (52%) children in the azithromycin group and 11 (33%) in the beta-lactam group met the definition for treatment failures (P = 0.34). Eight treatment failures while receiving azithromycin were caused by pneumococci with the macrolide-resistant (M) phenotype, 2 with the macrolide-, lincosamide- and streptogramin B-resistant (MLSB) phenotype and 1 by a macrolide-susceptible organism. In the beta-lactam group 7 had a penicillin-resistant isolate, 3 had an intermediately susceptible isolate and 1 had a susceptible isolate. CONCLUSIONS: Our study suggests that treatment failures among patients who developed invasive disease within 30 days of receiving an antimicrobial occur as frequently in patients who receive beta-lactam antibiotics as in those who receive azithromycin. Furthermore macrolide resistant organisms are not more likely to be recovered after a macrolide treatment failure than a penicillin-nonsusceptible isolate being recovered after a beta-lactam treatment failure (P = 1.0).

Anti-Bacterial Agents↗
PubMed2004

Ampicillin and penicillin concentration in serum and pleural fluid of hospitalized children with community-acquired pneumonia.

BACKGROUND: Optimal therapeutic efficacy of beta-lactam antibiotics for treatment of pneumococcal pneumonia is thought to be associated with the serum concentration greater than the minimum inhibitory concentration for 40-50% of the interdose interval at site of infection. OBJECTIVE: Establish whether intravenous administration of ampicillin 400 mg/kg/day or penicillin 200,000 IU/kg/day in 6 divided doses reaches serum and or pleural concentrations above 4 microg/ml for at least 40% of the interdose interval. MATERIALS AND METHODS: Hospitalized healthy children 1 month-14 years old with community-acquired bacterial pneumonia and empyema were eligible. Blood samples were obtained 30 min (C1) and 3 h (C2) after an antibiotic dose. Pleural fluid samples were obtained 1 and 4 h after the same dose in which blood samples were obtained. The concentrations were measured by high performance liquid chromatography. RESULTS: The study included 17 patients treated with ampicillin and 13 treated with penicillin. For ampicillin, mean serum concentrations were C1 37.3 +/- 19 microg/ml and C2 11 +/- 10.2 microg/ml and mean pleural fluid concentrations were C1 25.8 +/- 9.9 microg/ml and C2 16.2 +/- 7.9 microg/ml. For penicillin, mean serum concentrations were C1 21.8 +/- 16.4 microg/ml and C2 23.9 +/- 3.4 microg/ml. Mean pleural fluid concentrations were C1 10.9 +/- 2.2 microg/ml and C2 7.7 +/- 3.4 microg/ml. In 8 of 30 patients, serum C2 was <4 microg/ml; in all of them serum concentrations were >4 microg/ml for >40% of the interdose interval. CONCLUSIONS: This study of the pharmacokinetics of beta-lactam antibiotics in children with bacterial pneumonia may help in the development of therapeutic guidelines for the treatment of pneumococcal pneumonia.

Adolescent↗
PubMed2004

Community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children.

BACKGROUND: The clinical characteristics and virulence factors related to musculoskeletal infections caused by community-acquired, methicillin-resistant Staphylococcus aureus (MRSA) in children are not well-defined. METHODS: In this retrospective study, the demographics, hospital course and outcome of children with musculoskeletal infections were reviewed from medical records and by contacting patients or their physicians. Antimicrobial susceptibilities were determined by disk diffusion. Polymerase chain reaction was performed to detect genes encoding for virulence factors. Mann-Whitney, chi2 and Kaplan-Meier tests were used for statistical analysis. RESULTS: Community-acquired MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused musculoskeletal infections in 31 and 28 children, respectively. The median numbers of febrile days after start of therapy were 4 and 1 for MRSA and MSSA patients, respectively (P = 0.001). The median numbers of hospital days were 13 and 8 for the MRSA and MSSA groups, respectively (P = 0.014). At follow-up, 2 patients in the MRSA and 1 in the MSSA group had developed chronic osteomyelitis. pvl and fnbB genes were found in 87 and 90% versus 24 and 64% in the MRSA versus MSSA groups, respectively. (P = 0.00001 and 0.017). Ten patients with pvl-positive strains had complications versus no patients with pvl-negative isolates (P = 0.002). CONCLUSIONS: Febrile days and hospital days were greater in children with musculoskeletal infection caused by MRSA than in those affected by MSSA, but no significant differences were found in the final outcome. pvl and fnbB genes were more frequent in the MRSA than in the MSSA strains. The presence of the pvl gene may be related to an increased likelihood of complications in children with S. aureus musculoskeletal infections.

Adolescent↗
PubMed2004

St. Louis encephalitis in early infancy.

We describe a case of St. Louis encephalitis in a 19-day-old infant who presented with fever and seizure activity. To our knowledge, this is the youngest case of St. Louis encephalitis ever reported.

Acyclovir↗
PubMed2004

Clonality of Streptococcus pneumoniae serotype 1 isolates from pediatric patients in the United States.

We compared Streptococcus pneumoniae serotype 1 isolates causing disease among children in six geographic regions of the United States to determine genetic relatedness. Genomic fingerprints were determined by repetitive element polymorphism PCR (Rep-PCR). Multilocus sequence type characterization was performed on selected isolates. Four different genomic banding patterns were identified by Rep-PCR. One profile (clone 1) was predominant and matched sequence type 227.

Adolescent↗
PubMed2004

Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine.

OBJECTIVE: To monitor clinical and microbiologic features including antimicrobial susceptibility and serogroup distribution of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of routine administration of the 7-valent pneumococcal conjugate vaccine (PCV7). DESIGN: A 9-year (January 1, 1994 through December 31, 2002) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at 8 children's hospitals in the United States with culture-proven invasive infections caused by S pneumoniae. RESULTS: When compared with the mean of the years 1994 to 2000, the annual number of invasive pneumococcal infections for children < or =24 months of age declined 58% in 2001 and 66% in 2002. If only the serogroups in the PCV7 are considered, the number of cases in children < or =24 months old declined 63% and 77% in 2001 and 2002, respectively. The greatest decrease was observed for serogroup-14 isolates. The number of isolates in nonvaccine serogroups increased 28% in 2001 and 66% in 2002 for children < or =24 months old. Nonvaccine serogroup-15 and -33 isolates had the greatest increase in number. The proportion of all isolates nonsusceptible to penicillin increased yearly from 1994 to 2000, reached a plateau in 2001 at 45%, and declined to 33% in 2002. Decrease in nonsusceptibility to penicillin occurred entirely in the isolates with penicillin minimum inhibitory concentration > or =2 microg/mL. Nonsusceptibility to penicillin increased slightly among nonvaccine-serotype isolates. Most infections after at least 2 doses of PCV7 were caused by nonvaccine-serotype isolates. CONCLUSIONS: Since the introduction of the PCV7, the number of invasive pneumococcal infections caused by vaccine-serogroup isolates among 8 US children's hospitals has decreased >75% among children < or =24 months old. In addition, penicillin resistance decreased in 2002 for the first time since our surveillance began in 1993-1994. However, we have noted that replacement may be developing with serogroups 15 and 33. Furthermore, penicillin resistance seems to be increasing among nonvaccine serogroups. Surveillance must be continued to detect the emergence of changes in the distribution of serotypes as well as antibiotic susceptibility.

Child↗
PubMed2004

The changing face of pleural empyemas in children: epidemiology and management.

OBJECTIVE: Empyema remains a significant cause of morbidity in children. This study evaluates the changes that have affected the outcome in children with pleural empyema, including the emergence of resistant organisms, the introduction of the pneumococcal conjugate vaccine, and earlier treatment with video-assisted thoracoscopy (VATS). METHODS: A retrospective chart review was performed on all patients who were discharged with a diagnosis of empyema and community-acquired pneumonia over a 10-year period (1993-2002) at Texas Children's Hospital in Houston, Texas. Data collected included demographic information, clinical presentation, radiographic studies, laboratory data including culture results, and hospital course. RESULTS: A total of 230 charts were available for review. The mean age of the patients was 4.0 +/- 3.6 years. Of the pleural fluid cultures performed, 32% (69 of 219) were positive. An additional 27 patients had a cause identified by blood culture. The first penicillin-nonsusceptible Streptococcus pneumoniae was identified in 1995, and the first methicillin-resistant Staphylococcus aureus was identified in 1998. After the universal use of the pneumococcal conjugate vaccine, 3 major changes have occurred (1999-2000 vs 2001-2002): 1) the number of patients admitted with empyema (per 10 000 admissions) has decreased from 23 to 12.6; 2) the prevalence of S pneumoniae has decreased from 66% (29 of 44) to 27% (4 of 15); and 3) S aureus has become the most common pathogen isolated (18% vs 60%), with 78% of those being methicillin resistant. The use of early VATS (<48 hours after admission) versus late VATS (>48 hours after admission) significantly decreased the length of hospitalization (11.49 +/- 6.56 days vs 15.18 +/- 8.62 days). CONCLUSIONS: The microbiologic cause of empyema has changed with an increasing incidence of S aureus, particularly methicillin-resistant S aureus. The use of VATS for initial therapy of empyema results in decreased duration of fever and length of hospitalization.

Adolescent↗
PubMed2003

Hemophagocytic syndrome in children: an important diagnostic consideration in fever of unknown origin.

To study the evolution of hemophagocytic syndrome (HPS) in children, we performed a retrospective review of 19 patients (median age, 17.4 months) in whom an infectious diseases consultation was requested at Texas Children's Hospital during the period of September 1991 through September 2001. Clinical findings consistent with HPS most frequently presented during days 6-14 of illness, concomitant with laboratory abnormalities. Fever was present for a median of 19 days before the diagnosis of HPS. Elevated serum lactate dehydrogenase and ferritin levels were noted in all patients. An infectious agent was identified in 42% of patients; 16% were found to have immunologic or vasculitic disease. HPS is a rare but often fatal disease that can initially present as fever of unknown origin with varying clinical findings, and it can be recognized by physicians who are familiar with the evolution of HPS. It is likely that many of these cases remain undiagnosed because of the HPS's rapidly fatal course.

Adolescent↗
PubMed2003

Macrolide resistance among middle ear isolates of Streptococcus pneumoniae observed at eight United States pediatric centers: prevalence of M and MLSB phenotypes.

BACKGROUND: Increasing macrolide resistance among middle ear isolates complicates treatment of otitis media in children. When macrolide resistance is mediated via an efflux pump (M phenotype), the MICs of erythromycin, clarithromycin and azithromycin are usually below 32 microg/ml, and the pneumococcus remains susceptible to clindamycin. The association of prior specific macrolide therapy with the isolation of a macrolide resistant strain has not been reported. OBJECTIVES: To determine the mechanism of macrolide resistance in Streptococcus pneumoniae recovered from the middle ears of children with otitis media and their association, if any, with ethnicity, age, serogroup/serotype and prior antibiotic therapy. METHODS: Middle ear isolates collected by members of the United States Pediatric Multicenter Pneumococcal Surveillance Group during a 6-year period from September 1994 through August 2000 were studied. Antibiotic susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Disc diffusion susceptibility to erythromycin and clindamycin was performed to categorize macrolide resistance mechanisms. The medical record was reviewed to determine demographics and history of previous antibiotic therapy. Isolates were serogrouped or serotyped by the capsular swelling method. RESULTS: Of the 1088 isolates available for testing, 51% were nonsusceptible to penicillin and 37% were nonsusceptible to erythromycin. Erythromycin resistance increased form 15% in 1994 through 1995 to 56% in 1999 through 2000. Seventy-five percent of macrolide-resistant strains were M phenotype. Macrolide resistance was less likely in isolates recovered from African-Americans and more likely in isolates obtained from children <3 years of age and from isolates obtained at time of tympanostomy tube placement. Neither erythromycin, nor clarithromycin nor azithromycin prescribed in the 30 days before infection was more likely than another to be associated with increased macrolide resistance. However, any macrolide alone or in combination with another antimicrobial taken before infection was associated with increased macrolide resistance among the S. pneumoniae organisms isolated from the middle ear. CONCLUSIONS: Macrolide resistance among middle ear isolates of S. pneumoniae increased during the 6-year study. The proportion of M phenotype remained constant at 75%, meaning that these isolates remain susceptible to clindamycin. Continued surveillance to document potential changes is essential.

Anti-Bacterial Agents↗
PubMed2003

Clindamycin treatment of invasive infections caused by community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children.

BACKGROUND: Community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) is an established pathogen in several areas of the United States, but experience with clindamycin for the treatment of invasive MRSA infections is limited. We compared the outcome of therapy for MRSA with that of methicillin-susceptible (MSSA) invasive infections in children treated with clindamycin, vancomycin or beta-lactam antibiotics. METHODS: The demographics, hospital course and outcome of children at Texas Children's Hospital between February and November 2000 and between August 2001 and August 2002 with invasive S. aureus infections were reviewed from medical records in this retrospective study. RESULTS: CA-MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused invasive infections in 46 and 53 children, respectively. The median ages (range) of the children were: MRSA, 3.5 years (2 months to 18.6 years); MSSA, 4.8 years (3 months to 19.8 years). The sites of infection for MRSA vs. MSSA isolates, respectively, were: bacteremia, 3 vs. 6; osteomyelitis, 14 vs. 14; septic arthritis, 5 vs. 7; pneumonia, 11 vs. 3; lymphadenitis, 7 vs. 14; other, 5 vs. 8. Among MRSA patients 39 (20 received clindamycin only, 18 had vancomycin initially and 8 were treated with a beta-lactam initially) received clindamycin and 6 received vancomycin as primary therapy. Among MSSA patients, clindamycin, nafcillin or other beta-lactam antibiotics were used in 24, 18 and 9, respectively. The median number of febrile days was 3 (0 to 14) and 2 (0 to 6) for MRSA and MSSA patients, respectively (P = 0.07). The median number of days with positive blood cultures was 2 for the MRSA (n = 16) and 1 for the MSSA (n = 18) patients (P = 0.04). CONCLUSION: Clindamycin was effective in treating children with invasive infections caused by susceptible CA-MRSA isolates.

Adolescent↗