Sergio L. Vargas

Search for primary infection by Pneumocystis carinii in a cohort of normal, healthy infants.

To determine whether Pneumocystis carinii is associated with clinical illness in the competent host, 107 normal, healthy infants were enrolled in a 2-year prospective cohort study in Chile. P. carinii was identified by specific stains and nested--deoxyribonucleic acid (DNA) amplification of the large subunit mitochondrial ribosomal ribonucleic acid gene of P. carinii f. sp. hominis, and seroconversion was assessed by enzyme-linked immunosorbent assay of serum samples drawn every 2 months. P. carinii DNA was identified in nasopharyngeal aspirates obtained during episodes of mild respiratory infection in 24 (32%) of 74 infants from whom specimens were available for testing. Three (12.5%) of those 24 infants versus 0 of 50 infants who tested negative for P. carinii had apnea episodes. Seroconversion developed in 67 (85%) of 79 infants who remained in the study by 20 months of age and occurred in the absence of any symptoms of disease in 14 (20.8%). The study indicates that P. carinii DNA can be frequently detected in healthy infants, and it raises the hypothesis that they may be an infectious reservoir of P. carinii in the community. Further investigation is needed to identify whether P. carinii causes overt respiratory disease in infants.

Pneumocystis Colonization Is Highly Prevalent in the Autopsied Lungs of the General Population

BACKGROUND Increasing reports of Pneumocystis DNA in noninvasive respiratory specimens from immunocompetent asymptomatic adults and the characteristic lung tropism of Pneumocystis suggest that asymptomatic pulmonary infections with Pneumocystis occur after primary infection. However, studies searching for Pneumocystis in the autopsied lungs of healthy immunocompetent adults have not met with success. METHODS Lungs of people who died of violent causes (accidents, homicide, and suicide) and of nonviolent causes (diseases causing a rapid demise in the street) in Santiago, Chile-for whom an autopsy was legally required-were examined for Pneumocystis by nested polymerase chain reaction (PCR) DNA amplification of the mitochondrial large subunit ribosomal RNA-specific P. jirovecii gene and immunofluorescent microscopic analysis. Lung tissue concentration methods and analysis of approximately 3% of the weight of the right upper lobe (RUL) were needed to reach the sensitivity threshold of the assays. Individuals determined to be P. jirovecii negative after analysis of 3% of the RUL weight in the violent death group were confirmed to be negative by analyzing additional tissue, totaling 6%-7% of the RUL weight. RESULTS P. jirovecii was identified by nested PCR in 50 (64.9%) of 77 individuals (34 [61.8%] of 55 in the violent death group and 15 [78.9%] of 19 in the nonviolent death group; P > .05) and additionally by microscopic analysis in all individuals who tested positive for P. jirovecii DNA in the violent death group. Analysis of tissue beyond 3.0% of the RUL weight for the individuals who tested negative yielded consistently negative results. CONCLUSIONS A mild P. jirovecii pulmonary infection is prevalent in more than half of the general adult population. Our results strengthen the concept that immunocompetent adults develop frequent self-limited reinfections throughout life and participate in the circulation of P. jirovecii as an infective reservoir for susceptible individuals.

Association of Primary Pneumocystis carinii Infection and Sudden Infant Death Syndrome

To delineate clinical and histological features of the first Pneumocystis carinii infection affecting the immunocompetent host, P. carinii-specific histological stains were performed on autopsy lung specimens from 534 consecutive pediatric patients (those with AIDS and malignancies were excluded) in Santiago, Chile. P. carinii clusters were found in 4 (25%) of 16 infants who died of no apparent cause at arrival to the emergency department, and in 10 (2.9%) of 342 infants who died of multiple conditions at the hospital (P=.002, Fishers exact test). This prompted us to analyze additional series of infants with sudden infant death syndrome (SIDS). In 161 additional SIDS cases, 47 (35.1%) of 134 infants from Chile and 4 (14.8%) of 27 infants from Oxford, United Kingdom, were found to have P. carinii clusters in the lungs. The quantity of P. carinii cysts was small compared with the numbers seen in immunocompromised hosts with P. carinii pneumonitis. This study provides histological evidence that primary P. carinii infection is associated with SIDS.

Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin.

Background. Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci. Purpose and design. A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy. Results. A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents. No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79%vs. 81%); deaths (2%vs. 3%); seizures after enrollment (22%vs. 21%); and severe sequelae (14%vs. 14%). Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen. None of the evaluable patients experienced significant abnormalities of liver function during treatment. One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge. The episode resolved with liver function tests returning to normal within 2 months. Conclusions. We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis. These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections.

Azithromycin for treatment of severe Cryptosporidium diarrhea in two children with cancer

Two children with cancer received azithromycin for Cryptosporidium-associated diarrhea that was unresponsive to supportive care. One child had choleriform diarrhea requiring daily fluid replacement of up to 65% of his total body weight; the other had protracted diarrhea and wasting. In both cases, administration of azithromycin was followed by prompt clinical improvement.

High-Dose Azithromycin versus High-Dose Amoxicillin-Clavulanate for Treatment of Children with Recurrent or Persistent Acute Otitis Media

ABSTRACT Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged ≤2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged ≤2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged ≤2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.

Near-Universal Prevalence of Pneumocystis and Associated Increase in Mucus in the Lungs of Infants With Sudden Unexpected Death

We demonstrate that Pneumocystis reaches a >90% prevalence peak at 3–5 months of age and associates with increased mucus (MUC5AC), suggesting airway epithelium stimulation in infants during this age range. Host ability to clear mucus would determine pathogenic expression.

Pneumocystis colonization in older adults and diagnostic yield of single versus paired noninvasive respiratory sampling.

The presence of Pneumocystis was assessed in oropharyngeal wash specimens from 110 adults (median age, 76 years; age range, 69-95 years), 66 of whom had a paired nasal swab specimen. Pneumocystis jirovecii DNA was detected in 12.8% of oropharyngeal wash specimens, and the frequency increased to 21.5% in paired specimens. Pneumocystis colonization is prevalent in older adults. Double noninvasive sampling increases the diagnostic yield.

Detection of Pneumocystis carinii f. sp. hominis and Viruses in Presumably Immunocompetent Infants Who Died in the Hospital or in the Community

Fresh-frozen lung and tracheal-aspirate specimens obtained from 112 infants who died in Santiago, Chile, during 1998-2000 were analyzed for the presence of Pneumocystis DNA, by use of nested DNA amplification of the large subunit mitochondrial rRNA, and for the presence of viruses, by use of culture and immunofluorescence. Pneumocystis DNA was detected in specimens from 45 (51.7%) of 87 infants who died in the community and from 5 (20%) of 25 infants who died in the hospital (P=.006). Primary infection with Pneumocystis was highly frequent among infants who die unexpectedly in the community. Infection with viruses was more common in infants who died in the hospital.

Identification of Pneumocystis carinii in the lungs of infants dying of sudden infant death syndrome.

Background. Recently Pneumocystis carinii has been identified in a significant number of infants diagnosed as having died from sudden infant death syndrome (SIDS) in South America and Europe. Methods. We examined lung sections of 79 infants who died with a diagnosis of SIDS in Rochester, NY, and Connecticut for the presence of P. carinii. Results. Organisms with a characteristic silver stain appearance for P. carinii were identified in 14% of the lung sections. Conclusions. These data suggest that a possible link between some cases of SIDS and infection with P. carinii should be further evaluated and that infection of young infants may serve as an important reservoir for human P. carinii.