Biomedical subjects

Ram Yogev

Publications and source records attributed to Ram Yogev.

At least 37 records · Page 2Linked to original sources

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

Pharmacokinetic characteristics of ritonavir, zidovudine, lamivudine, and stavudine in children with human immunodeficiency virus infection.

STUDY OBJECTIVE: To evaluate and describe the parameters and characteristics of different drug regimens in children infected with human immunodeficiency virus (HIV). DESIGN: Randomized, open-label, multicenter study. SETTING: Pediatric HIV research clinics in the United States and Puerto Rico. PATIENTS: Twenty-one HIV-infected children, aged 3-14 years, who were clinically stable and treated with the same antiretroviral therapy for 16 weeks or longer. INTERVENTION: In step 1, children were randomized to receive one of three treatment regimens: zidovudine plus lamivudine, ritonavir plus zidovudine and lamivudine, or ritonavir plus stavudine. Patients originally assigned to the zidovudine plus lamivudine group in step 1 were eligible to progress to step 2 if their HIV RNA values at week 12, 24, or 36 were 10,000 copies/ml or greater but 100,000 copies/ml or less. In step 2 they received a regimen of ritonavir plus stavudine and nevirapine. MEASUREMENTS AND MAIN RESULTS: Seven children were randomized to each of the three treatment regimens. Concentrations of the agents were quantitated at steady state after observed doses, and the pharmacokinetic parameters were determined. Nevirapine concentrations were not determined. One child was excluded from analysis because pharmacokinetic parameters could not be estimated. Ritonavir oral clearance was slower in the pooled cohort of children who received stavudine compared with zidovudine and lamivudine. Stavudine oral clearance was marginally faster when combined with ritonavir and nevirapine compared with only ritonavir. CONCLUSION: Therapy for HIV is complex, and pharmacodynamic data indicate that relationships exist between systemic concentrations of antiretroviral drugs and virologic response. Careful drug interaction studies have not been conducted for all treatment regimens, and it will not be surprising if unexpected interactions are found. Pharmacokinetic studies to address these considerations should be viewed as a fundamental component of antiretroviral drug development, as they represent a tool to improve pharmacotherapy for HIV-infected children.

Adolescent↗

PubMed2003

Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study.

BACKGROUND: Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection. OBJECTIVE: We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States. METHODS: Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age. RESULTS: Cell-surface marker analysis demonstrated that age was an extremely important variable in 24 lymphocyte subset distributions measured as percentages or absolute counts--eg, the CD4 (helper) T cell, CD8 (cytotoxic) T cell, CD19 B cell, CD4CD45RACD62L (naive helper) T cell, CD3CD4CD45RO (memory helper) T cell, CD8HLA-DRCD38 (activated cytotoxic) T cell, and CD8CD28 (activation primed cytotoxic) T cell. The testing laboratory proved to be an important variable, indicating the need for using the same laboratory or group of laboratories to assay an individual's blood over time and to assay control and ill or treated populations. Sex and race-ethnicity were much less important. CONCLUSION: The results of this study provide a control population for assessment of the effects of HIV infection on the normal development and distribution of lymphocyte subsets in children of both sexes, all races, and all ethnic backgrounds from birth through 18 years of age in an urban population. This study's findings will also prove invaluable in interpreting the immune changes in children with many other chronic diseases, such as primary immunodeficiency, malignancy, rheumatoid arthritis, and asthma.

Adolescent↗

PubMed2003

Evaluation of multiple drug therapy in human immunodeficiency virus-infected pediatric patients.

BACKGROUND: An aggressive therapeutic approach for treatment of HIV in adults consists of combining five or more concurrent antiretrovirals. The clinical benefits of this regimen are often accompanied by increased toxicities. We report the safety and tolerance of multiple drug therapy in HIV-infected children. METHODS: A retrospective chart review was performed to identify HIV-infected children who received > or =5 concurrent antiretrovirals or 4 antiretrovirals plus hydroxyurea. Treatment success was defined as > or =1 log(10) decrease in plasma HIV RNA from baseline any time during multiple drug therapy. Toxicities were defined as a >Grade 2 change from baseline in laboratory values. RESULTS: Twelve patients received multiple drug therapy for 6 months, and 42% of patients continued to receive therapy for at least 1 year. No Grade 3 or 4 toxicities or laboratory abnormalities were reported. Treatment success occurred in 8 (83%) of 12 patients. Adherence was a determining factor in treatment success or failure. CONCLUSIONS: Treatment of HIV-infected children with multiple drug therapy was well-tolerated in this cohort. Treatment success occurred in most patients, with adherence affecting patients' likelihood of success. Larger controlled clinical trials in this patient population are necessary to determine whether the benefit of this therapeutic approach outweighs potential risks.

Adolescent↗

PubMed2003

Linezolid versus vancomycin for treatment of resistant Gram-positive infections in children.

BACKGROUND: Pediatric infections caused by resistant Gram-positive infections are an increasing concern with limited treatment options. Linezolid, a new oxazolidinone, is active against staphylococci, streptococci and enterococci. OBJECTIVE: To assess clinical efficacy and safety of linezolid vs.vancomycin in antibiotic-resistant Gram-positive infections in children. DESIGN Hospitalized children (birth to 12 years of age) with nosocomial pneumonia, complicated skin/skin structure infections, catheter-related bacteremia, bacteremia of unknown source or other infections caused by Gram-positive bacteria were randomized 2:1 to receive linezolid intravenously followed by oral linezolid or vancomycin and then by an appropriate oral agent. Treatment duration was 10 to 28 days. RESULTS: There were 321 patients enrolled (linezolid 219, vancomycin 102). Clinical cure rates were 79% vs.74% (P = 0.36) and 89% vs.85% (P = 0.31) for linezolid and vancomycin in intent-to-treat and clinically evaluable patients, respectively. Cure rates were similar by age and infection diagnosis. Pathogen eradication rates in microbiologically evaluable patients were high for linezolid and vancomycin, respectively, for methicillin-susceptible S. aureus (95% vs.94%; P = 0.82), methicillin-resistant S. aureus (88% vs.90%; P = 0.89) and methicillin-resistant coagulase-negative staphylococci (85% vs.83%, P = 0.87). In clinically evaluable patients, linezolid-treated patients required significantly fewer days of intravenous therapy compared with vancomycin-treated patients (8.0 +/- 4.8; 10.9 +/- 5.8 days, respectively; P < 0.001). In addition significantly fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19% vs.34%, respectively; P = 0.003). Hematologic events were uncommon and similar between treatment groups. CONCLUSIONS: Linezolid was well-tolerated and as effective as vancomycin in treating serious Gram-positive infections in children.

Acetamides↗

PubMed2003

Linezolid for the treatment of complicated skin and skin structure infections in children.

BACKGROUND: Gram-positive pathogens are a major cause of complicated skin and skin structure infections (CSSSIs) in children. Many pathogens are developing decreased susceptibility to currently used antibiotics, increasing the need for new therapies. Linezolid is well-tolerated and effective in the treatment of these infections in adults. OBJECTIVE: To evaluate the clinical efficacy and safety of iv/oral linezolid and iv vancomycin in children with Gram-positive CSSSIs. METHODS: Hospitalized children <12 years of age were randomized (2:1 ratio) to receive either linezolid 10 mg/kg iv every 8 h (with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h) or iv vancomycin 10 to 15 mg/kg every 6 to 24 h (according to age). Clinical response, tolerance and safety were evaluated at follow-up. The results of a subset analysis of patients with CSSSIs are presented here. RESULTS: One hundred twenty intent-to-treat patients (linezolid 80, vancomycin 40) with CSSSI were included in this analysis. Clinical cure rates for clinically evaluable patients with CSSSI did not differ between treatment groups (linezolid, 93.2% vs. vancomycin, 90.0%; P = 0.594). Significantly fewer linezolid-treated patients experienced drug-related adverse events than did vancomycin-treated patients (23% vs. 48%; P = 0.006). The percentages of patients with laboratory abnormalities, including selected hematologic parameters, were generally low and similar between the treatment groups. CONCLUSIONS: Linezolid given iv or orally was well-tolerated and safe. It was as effective as vancomycin in treating children with Gram-positive CSSSIs.

Acetamides↗

PubMed2003

Neonatal sepsis caused by Streptococcus bovis variant (biotype II/2): report of a case and review.

Streptococcus bovis is an uncommon cause of infection in neonates. However, S. bovis is capable of causing fulminant neonatal sepsis or meningitis that is indistinguishable clinically from that caused by group B streptococcus. S. bovis and S. bovis variant (sometimes referred to as S. bovis biotypes I and II, respectively) are phenotypically similar but may be differentiated by expanded testing. In adults, specific associations between disease states and different biotypes of S. bovis are apparent. No data exist on possible differences or clinical relevance of neonatal infection caused by different biotypes or newer species of S. bovis. We report a 3-day-old neonate with bacteremia and meningitis caused by S. bovis variant (S. bovis biotype II/2) and review the literature.

Bacteremia↗

PubMed2003

Streptococcus pneumoniae infections in the neonate.

OBJECTIVE: Streptococcus pneumoniae infections in the neonate (SPIN) are relatively unusual events (1%-11% of neonatal sepsis) but are associated with substantial morbidity and mortality. Previous reports suggest that invasive SPIN is associated with prolonged rupture of membranes, maternal colonization/illness, prematurity, early-onset pneumonia presentation (<72 hours), and high mortality (50%). The aim of this study was to review the current epidemiology and clinical course of SPIN. METHODS: The US Pediatric Multicenter Pneumococcal Surveillance Group has been prospectively monitoring S pneumoniae infections since 1993 in 8 children's hospitals. For this report, data were gathered retrospectively from the charts of neonates who were 30 days of age and younger and had SPIN from September 1993 to February 2001. All pneumococcal isolates were sent to a central laboratory for serogrouping/typing and susceptibility testing. RESULTS: Twenty-nine cases of SPIN were identified from a total of 4428 episodes of S pneumoniae infection in children. Sixty-six percent were male, and 55% were white; the mean age was 18.1 day (+/-8.2). Ninety percent of infants were >or=38 weeks' gestation. Two mothers had bacterial infections at delivery; 1 had S pneumoniae isolated from both blood and cervix, and 1 had clinical amnionitis. The primary diagnoses in the neonates were bacteremia (8), meningitis (8), bacteremic pneumonia (4), septic arthritis/osteomyelitis (1), and otitis media (8). Thirty percent of infants with invasive SPIN presented with leukopenia/neutropenia, but this did not predict poor outcome. The infecting pneumococcal serogroups were 19 (32%); 9 (18%); 3 and 18 (11% each); 1, 6, and 14 (7% each); and 5 and 12 (3.5% each). Twenty-six percent of invasive neonatal infections were caused by serogroups 1, 3, 5, and 12, which are not contained in the heptavalent pneumococcal vaccine. In contrast, 6% of invasive nonneonatal disease was caused by these same nonvaccine serogroups. Susceptibility testing demonstrated that 21.4% of isolates were penicillin nonsusceptible and 3.6% were ceftriaxone nonsusceptible. Three (14.3%) neonates with invasive SPIN died; all deaths occurred within 36 hours of presentation. Deaths did not appear to be related to pneumococcal serogroup or susceptibilities. CONCLUSIONS: Compared with previous studies of neonates with pneumococcal infection, this series showed that infants with SPIN were usually 2 to 3 weeks of age at presentation; likely to be full term; and ill with pneumonia, meningitis, and otitis media. This late-onset presentation was associated with an overall mortality rate of 10.3% (14.3% for invasive disease).

Adult↗

PubMed2003

Mycobacterium gordonae bacteremia in an asymptomatic adolescent with acquired immunodeficiency syndrome.

Mycobacterium gordonae is historically viewed as an organism with low pathogenic potential, but it has increasingly become implicated in clinical disease in immunocompromised hosts. Illness related to M. gordonae infection ranges from localized infections to rare cases of disseminated disease. This report describes treatment of the first case of occult M. gordonae bacteremia in an adolescent with AIDS.

AIDS-Related Opportunistic Infections↗

PubMed2002

Growth in human immunodeficiency virus-infected children receiving ritonavir-containing antiretroviral therapy.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children often suffer from impaired growth. Highly active antiretroviral therapy (HAART) successfully reduces HIV 1 (HIV-1) RNA to 400 copies/mL or less in many children. OBJECTIVES: To determine if age- and sex-adjusted growth z scores correlate with HIV-1 RNA level and if control of viral load for 48 and 96 weeks results in improved growth in children receiving highly active antiretroviral therapy. DESIGN: Secondary analysis of the cohort of children receiving ritonavir nested in a randomized, open-label, clinical trial. SUBJECTS AND METHODS: The Pediatric AIDS Clinical Trials Group Protocol 338 enrolled clinically stable, antiretroviral therapy-experienced, HIV-infected subjects aged 2 through 17 years. Using data from subjects randomized to ritonavir-containing regimens (n = 197), the association of growth z scores and HIV-1 RNA levels were examined. MAIN OUTCOME MEASURES: Age- and sex-adjusted weight and height z scores. RESULTS: Enrollment weights were comparable with age- and sex-adjusted norms, but subjects receiving ritonavir-containing antiretroviral therapy were significantly shorter (mean z score, -0.57 [29th percentile]; 95% confidence interval, -0.73 to -0.40). Higher HIV-1 RNA levels correlated with lower growth z scores (P<.01). Subjects achieving and maintaining HIV-1 RNA of 400 copies/mL or less through 48 and 96 weeks experienced worse growth than subjects with a less controlled viral load. CONCLUSIONS: In this pediatric cohort, a significant decline in height and weight z scores was found despite control of viral replication. Further studies of growth are necessary to assess if nutritional and hormonal adjuvants to highly active antiretroviral therapy should be considered to improve growth in HIV-infected children.

Adolescent↗

PubMed2002

Is noma neonatorum a presentation of ecthyma gangrenosum in the newborn?

Noma neonatorum was suggested as a distinct entity characterized by a gangrenous process of the nose, oral cavity, eyelids and perineum that was almost universally fatal in premature infants with Pseudomonas sepsis. We report the first case of noma neonatorum in a 26-week-gestation twin born in the United States. Our case is consistent with previous descriptions of noma neonatorum; however, we question the distinction between noma neonatorum and a neonatal presentation of ecthyma gangrenosum.

Diagnosis, Differential↗

PubMed2002

Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced children with human immunodeficiency virus infection.

BACKGROUND: The efficacy and tolerance of switching from zidovudine (ZDV) and lamivudine (3TC) in clinically stable HIV-infected children with incomplete viral suppression to stavudine (d4T), nevirapine (NVP) and ritonavir (RTV) has not been determined. Aim. To evaluate the safety, tolerance, antiviral activity and immunologic changes after the change to a three drug combination. METHODS: During a clinical trial in which HIV-infected antiretroviral-experienced children were initially randomized to receive d4T/RTV, ZDV/3TC/RTV or ZDV/3TC (Step 1), 48 children who had HIV RNA > or = 10,000 copies/ml after > or = 12 weeks of ZDV/3TC therapy in Step 1 were switched to d4T/NVP/RTV in Step 2. The proportion of children receiving therapy with HIV RNA < or = 400 copies/ml at Study Weeks 24 and 48 receiving d4T/NVP/RTV in Step 2 were compared with children receiving RTV-containing regimens in Step 1. RESULTS: At 24 weeks of treatment with d4T/NVP/RTV in Step 2, 48% (23 of 48) of children had HIV RNA < or = 400 copies/ml compared with 34% (31 of 92) and 47% (44 of 93) receiving d4T/RTV or ZDV/3TC/RTV for 24 weeks in Step 1; at 48 weeks virologic response was 44, 27 and 42% in Step 2 d4T/NVP/RTV, Step 1 d4T/RTV and Step 1 ZDV/3TC/RTV arms, respectively. CONCLUSIONS: A delay of 7 to 12 months in the initiation of protease inhibitor-containing combination therapy in children receiving dual nucleoside analogue therapy did not adversely affect the RNA response during the first 48 weeks of treatment.

Adolescent↗

PubMed2002

Six year multicenter surveillance of invasive pneumococcal infections in children.

OBJECTIVE: Monitor clinical and microbiologic features including antimicrobial susceptibility of invasive pneumococcal infections among children. DESIGN: A 6-year (September, 1993, through August, 1999) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proved invasive pneumococcal infection. RESULTS: During the 6-year period 2581 episodes of invasive pneumococcal infection occurred in 2498 children. Underlying conditions were present in 29% of the children. Of children without an underlying condition, 15% of the total infections occurred in those 25 to 60 months old. As the ages of the children advanced the proportion of cases classified as bacteremia declined, whereas the proportion classified as pneumonia increased. Also, as the ages of the children increased the proportion of isolates in serotypes/serogroups 1, 3 and 23 increased. whereas the proportion for serotype 14 diminished. During the 6 years of the study, there was a significant increase in the percentage of isolates intermediate or resistant to penicillin (P < 0.000001) or intermediate to ceftriaxone (P < 0.002). By the sixth year of the study, 37 and 11% of the isolates were nonsusceptible to penicillin or ceftriaxone, respectively. Antibiotic use in the 30 days before diagnosis of systemic pneumococcal infection occurred in 30 to 35% of the children for each of the 6 years. The overall case-fatality rate for children with systemic pneumococcal infection was 1.56%. Mortality was greatest in children >60 months old and in those with underlying conditions; mortality was not related to antibiotic susceptibility. CONCLUSIONS: The percentage of pneumococcal isolates recovered from children with systemic infection which were intermediate for penicillin or ceftriaxone or resistant to penicillin increased steadily during the 6-year period. There was also a trend toward increasing rates of resistance to ceftriaxone. The age and serogroup/serotype distributions of our patients support the recommendations to consider administration of the seven valent pneumococcal conjugate vaccine for all children 24 to 59 months old, with special consideration for selected groups.

Age Factors↗

PubMed2002

Invasive pneumococcal infections in children with asplenia.

BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. OBJECTIVE: To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. METHODS: Children with S. pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2,581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.

Child↗

PubMed2002

Recombinant glycoprotein vaccines for human immunodeficiency virus-infected children and their effects on viral quasispecies.

In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease.

AIDS Vaccines↗

PubMed2002

Quantification of human immunodeficiency virus type 1 proviral DNA by using TaqMan technology.

A protocol for quantification of human immunodeficiency virus type 1 (HIV-1) proviral DNA with the TaqMan technology was developed and validated. The assay was specific for HIV-1, with an analytic sensitivity of 10 copies and a linear dynamic range of >6 logs. Viral RNA levels, when at a stable state, were highly correlated with proviral DNA levels in 80 specimens of 18 HIV-infected children.

Antiretroviral Therapy, Highly Active↗

PubMed2002

Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae.

OBJECTIVE: The frequency of children who are hospitalized with pneumococcal pneumonia complicated by necrosis, empyema/complicated parapneumonic effusion, and lung abscess seems to be increasing. The factors that contribute to this increase are unclear; therefore, the objective of this study was to describe and compare the relative frequency, clinical characteristics, and outcome of hospitalized children with complicated pneumonia with those of children with uncomplicated pneumonia caused by Streptococcus pneumoniae in the era of antibiotic resistance. METHODS: A multicenter, retrospective study of 8 children's hospitals in the United States was undertaken. A total of 368 children who were hospitalized with pneumococcal pneumonia identified from patients enrolled in the US Pediatric Multicenter Pneumococcal Surveillance Study over the period from September 1, 1993, to January 31, 2000 were studied. Demographic and clinical variables, antibiotic susceptibility, pneumococcal serotypes, antimicrobial therapy, and clinical outcome in hospitalized children with complicated versus uncomplicated pneumococcal pneumonia were measured. RESULTS: A total of 368 patients with pneumococcal pneumonia were identified. Of the 368 isolates, 47 (12.8%) were intermediate and 37 (10.1%) were resistant to penicillin; 18 (5%) were intermediate to ceftriaxone, and 9 (2.5%) were resistant to ceftriaxone. A total of 133 patients met the criteria for complicated pneumonia and had a chest tube placed; 56 of these patients subsequently underwent decortication. The proportion of hospitalized patients with complicated pneumococcal pneumonia increased progressively over the study period from 22.6% in 1994 to 53% in 1999. Patients with complicated disease were older (median age: 45 vs 27 months) and significantly more likely to be of white race and have chest pain on presentation compared with patients with uncomplicated disease. Patients who had complicated disease and underwent decortication were more likely to have pleural fluid lactate dehydrogenase levels of >7500 IU/L compared with those patients who had chest tube placement alone. Fifty-three percent of children who were > or =61 months of age and were hospitalized had complicated pneumonia. This group of children accounted overall for 42% of the patients with complicated pneumonia, 48.2% of the patients who subsequently underwent decortication, and 44% of the patients who had received a course of antibiotics before diagnosis. Pneumococcal serotypes 1, 6, 14, and 19 were the most prevalent serotypes causing disease, with serotype 1 causing 24.4% of the complicated cases versus 3.6% of the uncomplicated cases. Ninety-eight percent of the patients in both groups recovered from their pneumonia. Antibiotic resistance was not found to be more prevalent in those patients with complicated disease. CONCLUSIONS: The relative frequency of complicated disease in hospitalized children with pneumococcal pneumonia is increasing. Patients with complicated pneumococcal disease were older and significantly more likely to be of white race compared with those patients with uncomplicated disease. Pneumococcal serotype 1 caused significantly more disease in patients with complicated versus uncomplicated pneumonia. Patients with complicated disease were not more likely to be infected with an antibiotic-resistant isolate.

Anti-Bacterial Agents↗

PubMed2002

The role of protease inhibitor therapy in children with HIV infection.

In comparison with HIV infection in adults, higher HIV RNA levels in children with perinatal HIV infection, differences in the natural history of HIV disease progression, and the presence of a relatively immature immune system contribute to the more complex and problematic nature of pediatric antiretroviral therapy. Current US treatment guidelines for pediatric HIV infection advocate aggressive therapy with potent combination antiretroviral regimens, to achieve profound and durable suppression of viral replication and preservation of immune function. The combination of a protease inhibitor (PI) and dual nucleoside reverse transcriptase inhibitors (NRTIs) is the most commonly recommended form of highly active antiretroviral treatment (HAART). However, use of PI therapy in pediatrics has been constrained by the lack of suitable drug formulations, a paucity of pharmacokinetic and safety data, and drug intolerance. Pharmacokinetic studies of PIs demonstrate frequent differences between children and adults, and greater variability among children, which has led to subtherapeutic dosage regimens and the development of viral resistance. The optimal dosage of many PIs in younger children is not yet known. A therapeutically important drug interaction associated with PIs is that occurring between the various PIs themselves, which allows lower doses of PI at less frequent intervals. Dual PI regimens will probably become more common, as they permit a simpler antiretroviral regimen, lower pill/medication burden, fewer adverse effects and improved adherence. Poor adherence to antiretroviral therapy remains the greatest barrier to overall success in the treatment of HIV-infected children. The key to improving adherence in HIV-infected children is to find treatment regimens that are better suited to their normal life. With improvements in existing PIs and the development of newer ones, simplification of current antiretroviral therapy to once-daily regimens without loss of potency should be achievable. PI-containing HAART has transformed HIV infection into a chronic illness, and HIV-infected children now live longer.

Child↗