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The heptavalent pneumococcal conjugate vaccine (PCV7) has been shown to reduce the incidence of acute otitis media (AOM) caused by Streptococcus pneumoniae by 34% and reduces the overall incidence of AOM by 6% to 8%. More recent studies have shown increases in the proportion of Haemophilus influenzae and Moraxella catarrhalis in the middle-ear fluid of PCV7-immunized children. There has been no report on the effect of PCV7 on all 3 bacterial pathogens combined, either in the middle-ear fluid or nasopharynx of individual children with AOM. We investigated the impact of PCV7 on nasopharyngeal colonization with bacterial pathogens during AOM in the pre-PCV7 and post-PCV7 vaccination eras. Four hundred seventeen children (6 months to 4 years of age) were enrolled onto AOM studies between September 1995 and December 2004. Of these, 200 were enrolled before the vaccine use (historical controls), and 217 were enrolled after the initiation of PCV7 vaccination (101 were underimmunized, and 116 were immunized). Although the nasopharyngeal colonization rate for S pneumoniae was not different between the 3 groups, a significantly higher proportion of PCV7-immunized children with AOM were colonized with M catarrhalis. Overall, the mean number of pathogenic bacteria types isolated from immunized children (1.7) was significantly higher than in controls (1.4). The increase in bacterial colonization of the nasopharynx during AOM could be associated with an increase in AOM pathogens and theoretically can predispose PCV7-immunized children with AOM to a higher rate of antibiotic treatment failure or recurrent AOM.

Objective: The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea., Design and Setting: Randomized, double-blind, placebo-controlled study in outpatient setting., Patients: Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study., Interventions: Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube., Main Outcome Measures: Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid., Results: The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days)., Conclusions: Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid.

Objective: We investigated the prevalence and the etiology of acute otitis media (AOM) in children with bronchiolitis to determine whether AOM in such children is due entirely or mainly to respiratory syncytial virus (RSV), in which case routine antimicrobial treatment would not be appropriate., Methods: The study group consisted of children aged 2 to 24 months with bronchiolitis. In patients with AOM at entry, nasal washings for RSV enzyme-linked immunosorbent assay were obtained, and Gram-stained smear, bacterial culture, and reverse transcriptase polymerase chain reaction to detect the presence of RSV were performed on middle-ear aspirates. Patients without AOM were reevaluated at 48 to 72 hours, 8 to 10 days, and 18 to 22 days., Results: Forty-two children with bronchiolitis were enrolled. Sixty-two percent had AOM at entry or developed AOM within 10 days. An additional 24% had or eventually developed otitis media with effusion. Only 14% remained free of both AOM and otitis media with effusion throughout the 3-week observation period. All patients with AOM had 1 or more bacterial pathogens isolated from one or both middle-ear aspirates. Of 33 middle-ear aspirates, Streptococcus pneumoniae was isolated in 15, Haemophilus influenzae in 8, Moraxella catarrhalis in 8, and Staphylococcus aureus in 2. Two middle-ear aspirates yielded 2 pathogens each; 2 aspirates had no growth. RSV was identified in 17 (71%) of 24 patients with AOM., Conclusion: Bacterial AOM is a complication in most children with bronchiolitis. Accordingly, in patients with bronchiolitis and associated AOM, antimicrobial treatment is indicated.

Objective: Current trends in the clinical presentation and management of children with epiglottitis at Children's Hospital of Pittsburgh were reviewed for the years 1988 to 1993., Methodology: The medical records of all patients diagnosed as having epiglottitis between July 1988 and June 1993 at the Children's Hospital of Pittsburgh were reviewed. An additional telephone survey was conducted among the primary care physicians of those patients to collect information regarding administration of Haemophilus influenzae type b (HIB) vaccines., Results: During the study period 28 children (age range, 11 months to 11 years, 10 months) were admitted with the diagnosis of epiglottitis. Cases declined remarkably in 1991. Fever, sore throat, and stridor were the usual symptoms. HIB was the most common cause of epiglottitis accounting for 21 cases. Candida albicans was recovered from the surface culture of the epiglottis in two patients. At least 11 children experienced vaccine failure: nine with polysaccharide vaccine and two with the conjugate vaccine for HIB., Conclusion: Cases of epiglottitis have declined dramatically since licensure of HIB conjugate vaccines for use in early infancy. At least 52% of the reported cases represent vaccine failures with the purified polysaccharide vaccine.

Countercurrent immunoelectrophoresis was used to detect H. influenzae type b antigen in sera of 65 consecutive infants and children with clinical and radiographic evidence of pneumonia. Antigenemia was observed in only one patient who also had H. influenzae type b bacteremia. Blood cultures from four other children were positive for H. aphrophilus (one), Streptococcus pneumoniae (two), and an alpha-hemolytic Streptococcus (one). The frequency of pharyngeal colonization with H. influenzae type b was similar in children with or without pneumonia. If H. influenzae type b was the cause of pneumonitis in the children studied, it occurred without bacteremia or antigenemia.

Infections caused by ampicillin-resistant Haemophilus influenzae type b are prevalent in Fairfax County, VA. In order to gain information on pharyngeal carriage of ampicillin-resistant H influenzae, oropharyngeal cultures were obtained from 249 young children. The study population comprised three groups: 90 healthy children (group A), 79 children who had finished a ten-day course of amoxicillin treatment for acute otitis media (group B), and 80 children who were brought to our office for treatment of purulent nasopharyngitis (group C). Approximately 60% of the children in each group carried Haemophilus in the oropharynx. H parainfluenzae was the predominant oropharyngeal species in group 1. H influenzae was predominant in the other two groups. Ampicillin-resistant Haemophilus sp organisms were recovered from 16% of children in group A, 25% of those in group B, and 17% of patients in group C. Recent exposure to ampicillin was associated with an increase in the recovery of ampicillin-resistant strains of Haemophilus.

Among children less than 12 years of age residing in Dallas County, Texas, and in the state of Minnesota we conducted prospective, active surveillance of invasive Haemophilus influenzae disease. During 18 months, 616 cases were identified, of which 600 were caused by type b organisms. The annual incidence of disease was significantly greater in Dallas than in Minnesota (109 v 68/100,000 children younger than 5 years of age, P less than .001) and was greater in Dallas, even when rates for white children in the two regions were compared (P less than .001). Other regional differences were observed. In Dallas, a larger proportion of cases were in children attending day-care centers (27% compared with 12% in Minnesota, P less than .001) and more patients attended day care for greater than 40 h/wk (56% compared with 30% in Minnesota, P less than .001). Outer membrane protein subtyping of isolates revealed that in Dallas 6U isolates were associated significantly with cases in black children who attended day care. In Minnesota, but not in Dallas, isolates with subtype 1H were associated significantly with cases in children in day care. These data indicate that there are regional differences in the epidemiology of type b Haemophilus disease that may relate to differences in strains, day-care practices, or other unknown cultural or environmental factors. Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease.

Cefoxitin, a parenteral cephamycin beta-lactam antibiotic was prospectively evaluated as a single drug alternative in 31 children with cellulitis and the results of therapy were compared retrospectively with those from prevailing multiple antibiotic therapy for cellulitis in 56 children. Periorbital and lower extremity cellulitis accounted for more than 60% of the cases in both study groups. The most common bacterial agents included Haemophilus influenzae, Staphylococcus aureus, and group A beta-hemolytic Streptococcus. In as many as 50% of the cases, no etiologic agent could be found. In addition to blood cultures, cellulitis leading edge aspirate cultures were helpful in establishing the etiologic diagnosis. Of 52 patients sampled in the combined studies, 21% had positive aspirate cultures in the presence of negative blood cultures. The outcome and mean duration of hospital stay were similar in both groups. No severe adverse reactions were encountered. The mean number of antibiotics used in the retrospective study was three (range 1 to 7) whereas cefoxitin alone was used in the prospective study. All organisms isolated in the prospective study were susceptible to cefoxitin. Single antibiotic therapy with cefoxitin appears to be as safe and as effective in the treatment of cellulitis in children as multiple antibiotic therapy.

Infections of the uvula are infrequently recognized and have been previously described only in association with group A streptococcal pharyngitis or Haemophilus influenzae type b epiglottitis. Three cases of H influenzae type b bacteremic uvulitis are described. In suspected cases of H influenzae type b uvulitis, a lateral neck radiograph should be performed and parenteral antibiotics initiated.

Sulfisoxazole, 75 mg/kg/d in two divided doses for 3 months, was administered in a double-blind placebo crossover study to 35 children aged 6 months to 5 years who had frequent recurring episodes of otitis media. There was a 40% reduction in the rate of otitis media among patients receiving sulfisoxazole compared with those receiving placebo (0.25 v 0.42 episode per patient-month) which did not depend on age, sex, season, or several other factors. Using a randomized order, among patients who received placebo first, there was a 64% reduction on sulfisoxazole therapy compared with placebo (0.20 v 0.56 episode per patient-month). In this subgroup, there was significant improvement in eustachian tube function according to serial tympanograms. In the patients who received sulfisoxazole first, the rate of acute otitis remained low on placebo (0.28 v 0.30 episode per patient-month), and tympanogram patterns continued to improve after discontinuation of the active drug. These differences suggest a carry-over effect from the benefits of chemoprophylaxis. There was no significant difference in the species or sensitivity patterns of bacteria isolated from patients receiving sulisoxazole or placebo. Sulfisoxazole chemoprophylaxis appears to be safe and effective in significantly reducing episodes of otitis media and improving tympanogram patterns.

Meningitis due to Haemophilus influenzae serotype b biotype II occurred in a 2-year-old child who attended a nursery school along with 26 other 2-year-old children. Nasal swabs from these 26 contacts revealed a H influenzae type b colonization rate of 50% (13/26); simultaneously performed throat swabs detected a colonization rate of 4% (1/26). Biotyping of the H influenzae type b isolates revealed that only 46% (6/13) were the same biotype as the index case; the remaining seven isolates were biotype III. All children received treatment with 20 mg/kg/day of rifampin administered by the nursery school attendant as a single dose for four days before the results of the cultures were known. Eradication of H influenzae type b carriage was successful in three of the six biotype II carriers and five of the six biotype III carriers available for follow-up culture. It was concluded that: (1) the culture site utilized in determining H influenzae type b colonization rates may markedly influence the results obtained; (2) biotyping may be a valuable epidemiologic tool in investigating the contacts of patients with H influenzae type b disease, and (3) failures of rifampin to eradicate the carriage of H influenzae type b from the nasopharynx may occur. The prudent approach to the management of young contacts of patients with serious H influenzae type b disease is to recognize their high risk status and to maintain close surveillance of them. The role of chemoprophylaxis with rifampin remains to be established.

The Haemophilus influenzae type b polysaccharide vaccine was licensed for use in the United States in April 1985. Postlicensure case-control efficacy studies have yielded markedly different estimates of efficacy, leading to contradictory recommendations to practicing physicians. To obtain additional information about the efficacy of the vaccine, we studied cases of invasive Haemophilus influenzae type b disease ascertained through active surveillance in areas with a total population of 34 million. We enrolled children 24 to 59 months of age who did not attend day-care centers. (Data from our day-care study have been published elsewhere.) For each case child, as many as three 24- to 59-month-old control children were chosen from a roster of acquaintances supplied by the child's parent. Conditional logistic regression was used, and vaccine efficacy was estimated to be 62% (95% confidence interval = 0%, 85%), which did not change significantly after adjusting for age and parental smoking, variables that were significantly different for case and control children. Results of this study support our previous finding of a positive protective efficacy, albeit lower than the efficacy of 90% found in children 18 to 71 months of age in the Finnish prelicensure trial.

Cephalexin was compared to ampicillin for the treatment of otitis media in a randomized study. Bacteriologic diagnosis was sought by needle tympanocentesis in 179 children. No overall statistically significant differences were noted between the two groups; however, 20 patients who received cephalexin had a poor response to therapy whereas only five recipients of ampicillin responded poorly. A significant difference (P less than .05) between the two regimens was noted when Hemophilus influenzae was recovered. Fifty per cent of the children with H. influenzae otitis media who were treated with cephalexin responded poorly; no patients receiving ampicillin had a poor response. Our data suggest that the use of cephalexin monohydrate is not warranted for treatment of otitis media due to H. influenzae even when the isolate proves sensitive to this drug in vitro. In selected patients with otitis media caused by Staphylococcus aureus which is resistant to penicillin, cephalexin may provide effective treatment.

Strategies for management of children attending day-care facilities after a case of Haemophilus influenzae type b disease are controversial. The success of chemoprophylaxis in preventing subsequent cases has been variable. Failure of rifampin prophylaxis as currently recommended may result from usage limited to direct contacts of the index patient. This prospective study was designed to ascertain the extent of colonization in household contacts of colonized children attending day-care facilities with an index case of H influenzae disease. Outer membrane protein analysis was used to determine similarity between strains isolated from contacts and index patients. Of children attending six day-care facilities, 15% were colonized with subtypes of H influenzae identical with those of their respective index patients, and 7% of children were colonized with different subtypes. Colonization with identical outer membrane protein subtypes in children from day-care homes was more frequent than in the larger day-care centers (91% v 8%, P less than .00001). Within families of children with identical outer membrane protein subtypes, 25% of household members (17% of parents and 44% of siblings) were colonized despite lack of direct contact with the index patients. This colonization rate was comparable to that of household contacts of index patients (26%). Among household contacts of index patients, especially siblings, colonization with H influenzae tended to be lower if the patient attended day care than if the patient did not attend day care (17% v 73%; P = .05 for siblings). We have found that household contacts of colonized day-care children are a reservoir of H influenzae.(ABSTRACT TRUNCATED AT 250 WORDS)

A 7-month-old child developed beta-lactamase negative Haemophilus influenzae type b meningitis which was treated with parenteral ampicillin and chloramphenicol for two days and ampicillin for eight additional days. She was readmitted two days after discharge on the 14th day after the initial hospitalization because of a suspected relapse of meningitis. Cultures of CSF and blood yielded no growth, and therapy with ampicillin and chloramphenicol was discontinued after three days. After discharge, her fontanel became full and a large, right, frontoparietal brain abscess was found on her third admission on day 25. Pus from the abscess yielded beta-lactamase negative H influenzae type b but CSF and blood yielded no growth. The abscess resolved after needle aspiration of pus and 4 weeks of therapy with ampicillin and chloramphenicol. It is speculated that this rare complication of H influenzae meningitis arose from a focal infection in an area of brain necrosis that resulted from the initial meningitis.

The risk of Haemophilus influenzae septicemia/meningitis to children who have sickle cell anemia (SS) has been determined to be greater than that seen among normal infants. Of ten bacteriologically proven cases, eight episodes of infection were observed among 234 children with sickle cell anemia (645 person-years), who were less than 5 years of age. There was one case per 69 infants with sickle cell anemia who were less than 18 months old and one case per 36 children with sickle cell anemia between 19 and 59 months of age. Unexpectedly, two infections occurred among 224 children (824 person-years), aged 5 to 9 years; both died. Contrary to the rapid clinical course of pneumococcal infections in children with sickle cell anemia H influenzae septicemia was regularly heralded by a greater than 24-hour prodrome of upper respiratory tract infection, low-grade fever, and otitis media. Three (30%) preventable deaths occurred. Antibiotic therapy for the febrile child with sickle cell anemia must be predicated on the known 400-fold increased risk of pneumococcal septicemia in those less than 5 years old and the fourfold risk of H influenzae septicemia in those less than 9 years of age.

Three hundred one episodes of fever greater than or equal to 103 F were documented in 375 infants and young children observed in a comprehensive care clinic during the period October 1974 to October 1978. Of such highly febrile illnesses 79% were accompanied by respiratory tract signs or symptoms, 7% by disease at a site other than the respiratory tract, and 22% of illnesses had no localizing signs or symptoms. Viral cultures were obtained from the respiratory tract in 178 cases and were positive in 68: 57/134 from respiratory illness; 2/4 from illness at sites other than the respiratory tract; and 9/40 in children without localizing disease. Bacterial cultures of the upper respiratory tract were obtained in 191 illnesses, but the overall rate of isolation of Haemophilus influenzae, Streptococcus pneumoniae and group A streptococci (46%) did not differ from that in a group of well children (39%). Bacterial cultures of the blood were obtained in 89 patients with fever greater than or equal to 103 F and in an additional 41 children with lower temperatures. Nine children had documented systemic bacterial disease (eight positive blood cultures and one positive CSF). The rate of clinically apparent systemic bacterial disease in these otherwise normal infants was one bacteremic episode per 94 years of child care.

A case of Haemophilus influenzae type b meningitis in a neonate from whom both a beta-lactamase-negative and a beta-lactamase-positive strain were isolated simultaneously is reported. Both bacteriology laboratory technicians and clinicians should be aware of this phenomenon when performing sensitivity tests on H influenzae isolates or treating patients with serious H influenzae infection.

The relationship between the magnitude of bacteremia due to Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis and the clinical diagnosis was determined on 79 children who were not receiving prior antibiotic therapy and had fever, either in the presence or absence of focal signs of infection. Bacteremia was quantitated by the recently described Quantitative Direct Plating procedure in which heparinized blood (0.5 ml each) is plated onto blood and chocolate agar plates. Additionally, blood was cultured by means of the radiometric Bactec technique. In the case of H. influenzae and S pneumoniae, 23 (92%) of 25 patients with more than 100 organisms per milliliter of blood had meningitis or epiglottitis in contrast to only four (9.5%) of 42 patients with less than 100 organisms (P less than .001). No significant difference was noted in the magnitude of bacteremia due to N meningitidis among 12 patients with meningitis or other serious infections. The possible predictive value of the quantitation of bacteremia is illustrated by the observation of three children with seemingly mild respiratory infection and counts in excess of 100 organisms per milliliter who, within 20 hours, developed meningitis or epiglottitis. High bacterial counts of H influenzae and S pneumoniae in excess of 100 organisms per milliliter of blood should alert the physician to the existence or possible development of serious disease.

To determine the etiology of apparent meningococcemia, all cases of sepsis with coagulopathy, purpura, and/or adrenal hemorrhage (Waterhouse-Friderichsen syndrome) with and without shock occurring over a 12-year period were reviewed. A total of 42 cases were identified; 30 cases were caused by Neisseria meningitidis and 12 cases were caused by Haemophilus influenzae. Compared with patients with disease caused by H influenzae, patients with meningococcal disease were older, more often male, more often contracted the disease in winter-spring, and had a longer duration of antecedent symptoms; however, none of these differences was statistically significant. All patients were febrile (greater than 38 degrees C) and appeared toxic. Similar proportions in each group had shock and disseminated intravascular coagulopathy at the time of admission. Ten of 12 patients with H influenzae infection compared with 15/30 (P less than .05) with meningococcal infection were lethargic or comatose at the time of admission. Nine of 12 patients with H influenzae infection died compared with 5/30 with meningococcal disease (P less than .005); the mean time from onset of symptoms to death with H influenzae infection (20.7 +/- 11.4 [SE] hours) was significantly shorter (P less than .05) than with meningococcal infection (120 +/- 74.4 hours). Children with clinical signs of sepsis and with purpura, petechiae, or coagulopathy may have N meningitidis or H influenzae as etiologic agents. Initial antibiotic therapy should be directed against these pathogens.

Recent experience in the diagnosis and management of Hemophilus influenzae b pericarditis is described in five children. Anterior pericardectomy appears to be the preferred method of surgical drainage because it was associated with a shorter hospitalization than pericardiocentesis or closed or open pericardotomy and removed the risk of recurrent cardiac tamponade and constrictive pericarditis. Countercurrent immunoelectrophoresis of sera and pericardial fluid was used to rapidly identify the etiology of pericarditis in four of four patients tested. The observation that three children appeared to develop pericarditis in the absence of a contiguous infectious focus suggests that bacteremic seeding of the pericardium may be important in the pathogenesis of this disease.

A review of 72 cases of epiglottitis seen at the Children's Hospital of Denver was undertaken to determine the incidence of extraepiglottic and septic foci in this disease. A parallel review of the literature was also undertaken. The clinical, bacteriologic, laboratory, and radiologic findings of this patient population are described. A 25% incidence of both pneumonia and cervical lymphadenitis was found to be associated with this illness. Exudative tonsillitis and otitis media were the only other complications, although they were infrequently noted. No cases of septic arthritis or meningitis were encountered, although 50% of these patients were recognized as bacteremic. A low incidence of septic complications (eight cases of meningitis and one case of periarticular abscess) is noted in a review of the literature. Recommendations for antibiotic management and definition of the population at risk for septic complications are given.

Simultaneous cultures of conjunctivae and middle ear exudates were obtained from 20 episodes of the syndrome of purulent conjunctivitis and otitis media. Paired cultures from 18 episodes yielded Haemophilus influenzae at both sites. In two cases with prior topical antibacterial therapy of the conjunctivitis, H influenzae was isolated from the middle ear exudate only. Biotyping and outer membrane protein analysis of H influenzae isolates from five patients demonstrated that: conjunctival and middle ear strains were concordant in all cases, and all five patients had different strains. The conjunctivitis-otitis media syndrome is most often caused by strains of nontypable H influenzae of diverse clonotype.

We conducted a multicenter trial designed to assess the efficacy of three different drug regimens on eradication of Haemophilus influenzae type b (HIB) from the nasopharynx of household contacts of patients with invasive type b Haemophilus disease. The drug regimens studied were rifampin, 20 mg/kg, once daily for four days; rifampin, 10 mg/kg, twice a day for four days; and placebo, once daily for four days. Shortly after admission of the index patient to the hospital, 26% of 492 household contacts were found to be colonized with HIB. Both rifampin regimens eradicated carriage significantly better than placebo at 10 and 30 days (P = .001). However, among contacts whose cultures were initially negative, new acquisition of the organism occurred infrequently in this 30-day follow-up period regardless of the drug or placebo regimen prescribed. We also measured the concentration of anticapsular antibody in sera obtained from contacts younger than 6 years of age. Samples were obtained soon after admission of the index patient to the hospital and 30 days later. Several carriers younger than 2 years of age had low concentrations of antibody in both specimens. In contrast, nearly all carriers 2 to 5 years of age had high concentrations of antibody even in the first sample. Children who were not carriers usually had low antibody concentrations which did not increase during the period of observation. Our results suggest that most intrafamilial spread of HIB occurs prior to hospitalization of the index patient and stimulates immunity in contacts older than 2 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of cefaclor and rifampin in eradicating Haemophilus influenzae type b (HITB) from the nasopharynx of day care center and household contacts of children with HITB meningitis was evaluated. In 38/50 children treated with cefaclor, the carrier state persisted, a failure rate of 76%. Although cefaclor failed to eradicate HITB from many carriers, an appreciable reduction in the intensity of colonization following treatment was noticed. When rifampin was used in 17 children who had failed to respond to cefaclor, persistence of the carrier state with HITB was found in only two children, a failure rate of only 12%. During the study, two episodes of invasive HITB disease were documented to be acquired from sources other than the index cases or from children who were screened, which suggested the need to reevaluate the usually recommended strategy to screen for carriage and to treat only the immediate contacts 6 years of age and younger. Furthermore, the most appropriate agent for eradicating nasopharyngeal carriage of HITB awaits additional studies.

The pharmacokinetics of chloramphenicol following intravenous and oral administration were studied in 14 infants with Haemophilus influenzae meningitis. Following five days of treatment with intravenous chloramphenicol (100 mg/kg/day every six hours), oral chloramphenicol was substituted at the same dose. Multiple serum levels of chloramphenicol were determined after an intravenous dose on day 4 and after an oral dose on day 10. CSF levels were measured six hours after intravenous or oral chloramphenicol dose on those days (CSF trough). Following intravenous administration, the mean peak serum level of 15.0 micrograms/ml was reached at 45 minutes. In comparison, after oral chloramphenicol in the same dosage, the mean peak serum level of 18.5 micrograms/ml was achieved at two to three hours. The mean serum half-life of the drug (6.5 hours) was significantly longer after oral administration than after intravenous chloramphenicol (4.0 hours) (P less than .001). The increased serum half-life following orally administered chloramphenicol was occasionally associated with drug accumulation. In addition, mean trough CSF levels were somewhat higher when the patient received oral medication (6.6 micrograms/ml) compared to intravenous administration (4.2 micrograms/ml) (P less than .001). For any treatment regimen for H influenzae meningitis that includes a period of oral chloramphenicol therapy the patient should be hospitalized to ensure compliance. Because of the wide range of individual variation in serum half-life that may result in accumulation, periodic monitoring of serum chloramphenicol levels is also recommended.

Eleven cases of Hemophilus meningitis seen in the last year are reported. Three were H. parainfluenzae and eight were H. influenzae. The number of patients is small but probably indicates that there is little difference in the clinical or laboratory data in meningitis caused by these two organisms. The children with H. parainfluenzae tended to be less anemic and had more normal admission spinal fluid sugars and proteins, but this was probably because these patients were older and had shorter prodromes. As more cases of H. parainfluenzae meningitis are noted, it seems likely that there will not be any difference in the clinical or laboratory data. Two of the three cases of H. parainfluenzae meningitis had the complication of ataxia secondary to severe bilateral vestibular deficits. Finally, it should be noted that these two organisms will not be distinguished by routine bacteriological studies, and that differentiation must be carried out by an experimental laboratory.

One hundred forty-four serous and mucoid effusions were cultured for aerobic bacteria, Mycoplasma pneumoniae, and virus. Thirty percent of all effusions yielded an unequivocally positive culture for aerobic bacteria. Although serous effusions were culture positive as often as mucoid effusions, Haemophilus influenzae was isolated predominantly from serous effusions and Staphylococcus epidermidis predominantly from mucoid samples. Only one of 73 effusions yielded a viral isolate (Herpesvirus hominis). None of 33 effusions yielded M pneumoniae, and only one of 17 effusions yielded an anaerobe (Propionibacterium). These findings suggest that aerobic bacteria may play a role in the pathogensis of serous and mucoid otitis media.

Hrom February 1974 through May 1975, 58 isolates of ampicillin-resistant Hemophilus influenzae from patients were submitted to the Center for Disease Control from 23 states and the District of Columbia. The epidemiologic characteristics of these widely scattered cases were strikingly similar to those of cases previously reported from individual communities or institutions. Because of the nationwide distribution of resistant isolates and the adverse consequences of ineffective therapy, the use of chloramphenicol is recommended for the initial management of systemic illness definitely or probably due to H. influenzae type b.

The records of 129 patients admitted to the hospital with the findings of fever and petechiae were reviewed to determine the incidence of invasive bacterial disease in patients with this symptom complex. Twenty-six patients (20.2%) had culture-proven bacterial infections; 13 (11.1%) of the group had Neisseria meningitidis, eight had Haemophilus influenzae type B. No single laboratory test was sufficiently sensitive to detect all patients with life-threatening bacterial infections, but a combination of normal laboratory findings was highly specific for those without significant disease.

Two children are reported whose nephrotic syndrome was complicated by peritonitis due to H. influenzae type b. In Pittsburgh, the leading organism for peritonitis in nephrosis remains D. pneumoniae with a disproportionately high incidence in black children. Although H. influenzae is a rare cause of this complication, it should be considered along with the other previously recognized etiological bacterial agents.

The potential clinical value of quantitative blood cultures determined by a commercially available lysis-direct plating method was studied in 50 children with either Haemophilus influenzae or Streptococcus pneumoniae bacteremia. The magnitude of bacteremia correlated with the severity of the infection; patients with greater than or equal to 100 colony-forming units per milliliter were significantly more likely to have meningitis (P less than .01, chi 2 = 7.5). On the other hand, all patients with S. pneumoniae bacteremia with colony counts lower than 15 colony-forming units per milliliter had "occult bacteremia" with no focus of infection. The data suggest that patients with higher levels of bacteremia have more severe disease. Quantitative blood culture results may be helpful in identifying which children are at risk for invasive disease.