Biomedical subjects
Publications and source records attributed to S A Chartrand.
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Pertussis is well controlled in the United States by routine childhood immunization. In contrast, this disease is endemic and epidemic in Germany because routine immunization has not been implemented. To gain information relating to the epidemiology of Bordetella pertussis infections, we examined the prevalence and magnitude of B. pertussis agglutinins and of IgG and IgA antibodies (detected by enzyme-linked immunosorbent assay) to four B. pertussis antigens--lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in the sera of 119 American university students and 119 German military recruits of similar age. Geometric mean titers of agglutinins and geometric mean values for IgG antibodies to the four antigens were two- to threefold higher in sera from the American students than in sera from German recruits. In contrast, the geometric mean IgA values and the percentage of subjects with detectable IgA antibodies to the four antigens were similar in the two populations. Since IgA antibody results mainly from infection and not from immunization, our data suggest that B. pertussis infections are common among both American and German young adults despite the marked difference in rates of clinical pertussis in the two countries.
From January, 1992, to January, 1994, penicillin-resistant (minimal inhibition concentration (MIC) > 0.06 microgram/ml) Streptococcus pneumoniae (PRSP) isolates accounted for 48 (17%) of 283 isolates from acute otitis media (AOM) or recurrent AOM in 246 ambulatory patients in rural Kentucky. By broth microdilution, relatively penicillin-resistant (MIC > 0.06 to 1.0 microgram/ml) and highly penicillin-resistant (MIC > or = 2.0 micrograms/ml) strains were detected in 25 (16%) and 23 (15%), respectively, of 157 pneumococcal middle ear isolates. Using 1994 National Committee for Clinical Laboratory Standards breakpoints for pneumococci (unavailable for oral cephalosporins except cefuroxime), highly PRSP strains were almost uniformly susceptible to clindamycin and vancomycin. In contrast highly PRSP strains were resistant to most oral antimicrobials customarily used for AOM with one-third of strains highly resistant (MIC > or = 2.0 micrograms/ml) to ceftriaxone. Serotypes 6B, 19F and 23F accounted for 95% of highly PRSP strains and serotype 9V for 48% of relatively PRSP strains. By multivariate analysis, otitis-prone condition (P = 0.0008) and number of antibiotic courses before day of culture (P < 0.0001) were independently predictive of PRSP. Highly PRSP isolates were more commonly isolated from patients recently treated within 3 days (30%) vs. those who completed therapy more than 3 days earlier (2%) (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
We obtained nasopharyngeal cultures for Streptococcus pneumoniae from 54 children ages 2 to 24 months attending an Omaha child-care center (CCC) in April 1994. Thirty-two (59%) of the 54 children were colonized with S. pneumoniae belonging to serotypes 23, 19, 6 and 11. Seventeen (53%) of the pneumococcal isolates were highly resistant to penicillin (minimal inhibitory concentration > or = 2.0 micrograms/ml; HR-SP) and 7 (22%) were intermediately resistant to penicillin (0.12 < or = minimal inhibitory concentration < or = 1.0 microgram/ml; IR-SP). Within each pneumococcal capsular serotype, there were 1 to 3 DNA subtypes based on pulsed field gel electrophoresis analysis. A single pulsed field gel electrophoresis strain predominated in most CCC rooms, suggesting horizontal transmission among cohorted children. Nasopharyngeal cultures obtained 4 months later revealed similar S. pneumoniae colonization rates (28 of 52, 54%); however, only 2 (7%) of 28 isolates were HR-SP and 11 (39%) were IR-SP. Colonization with resistant pneumococci persisted after 4 months in 4 (12%) of 34 children cultured on both occasions. Antibiotic use by attendees had decreased notably between the two sampling periods, suggesting that selective pressure within the CCC might contribute to seasonal variation in colonization rates with HR-SP and IR-SP. We conclude that multiple genetic clones of penicillin-resistant pneumococci can occur simultaneously in a single CCC, especially during periods of heavy antibiotic selection pressure. However, individual clones of penicillin-resistant S. pneumoniae may be spread from child to child, suggesting that colonization with penicillin-resistant S. pneumoniae should now be considered a CCC-associated phenomenon.
In this randomized, investigator-blinded multicenter study, tympanocentesis for acute otitis media with effusion in 137 ears from 108 children, 6 months to 12 years of age, revealed 84 definite pathogens and 32 potential pathogens. Twenty-nine aspirates from 23 subjects were sterile. Of the 116 isolates 42 (36%) were Streptococcus pneumoniae, 24 (21%) were Haemophilus influenzae, 9 (8%) were Moraxella catarrhalis, 9 (8%) were Streptococcus pyogenes and 1 (1%) was Staphylococcus aureus. Twenty-two (19%) definite pathogens produced beta-lactamase. Patients were randomized to cefixime (8 mg/kg/day daily) or cefaclor (40 mg/kg/day divided into two doses). Efficacy was determined by pneumatic otoscopy and tympanometry at the end of therapy visit on Days 11 to 14 and up to 4 weeks of follow-up. At end of therapy subjects with definite pathogens exhibited a satisfactory clinical outcome in 26 of 36 (72%) ears for cefaclor and 40 of 48 (83%) ears for cefixime recipients (P = 0.12). For ears with beta-lactamase-producing isolates there were no (0 to 12) cefixime failures but 4 of 10 cefaclor failures (P = 0.03). Diarrhea/loose stools were more frequent in cefixime (16 of 58) than cefaclor (4 of 50) recipients. One cefixime subject required discontinuation of drug. Overall efficacy for treatment of acute otitis media with effusion was not different; however, cefixime appeared more effective for infections caused by beta-lactamase-producing organisms.
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OBJECTIVE: To prospectively characterize varicella occurring in children previously immunized with a live attenuated varicella vaccine (breakthrough varicella) through daily observation by medical personnel and to compare it with natural varicella followed in the same manner. DESIGN: A blinded clinical survey. SETTING: Four pediatric practices (two private; two hospital-based). PARTICIPANTS: Healthy 12-month-old through 17-year-old children with chickenpox were studied; 92 had natural varicella and 58 had breakthrough varicella. SELECTION PROCEDURES AND INTERVENTIONS: Study personnel, unaware of vaccination status, documented the clinical characteristics of each patient in the office or at the patient's home each day from enrollment until the day after the total number of lesions increased less than 10%. A standard form documenting number and description of lesions, temperature, duration of illness, and associated clinical complaints was completed each day by the same study personnel. Acute and convalescent sera were obtained on breakthrough cases. MEASUREMENTS AND RESULTS: Antibody to varicella-zoster virus was measured by the glycoprotein-based enzyme-linked immunosorbent assay. Of those with sera available, 85% were serologically confirmed. Eighty-seven percent of enrollees had a known exposure to chickenpox, with at least two thirds of each group having a greater than 4-hour or a household exposure. The numbers of total and vesicular lesions were significantly higher in the natural varicella group, regardless of exposure status (P = .021 to < .001). The group with breakthrough varicella had a significantly lower incidence of fever (P < .001) and a significantly shorter duration of illness (P < .001). Other associated constitutional complaints and complications were not significantly different between groups. CONCLUSION: Varicella in vaccine recipients is clinically modified and significantly less severe than natural disease.
A case of localized neonatal herpes simplex virus (HSV) infection involved a prior fetal scalp electrode site. Rupture of the fetal membranes, placement of the fetal scalp electrode and delivery occurred within 30 minutes. The mother had no previous history of genital lesions, and no herpetic lesions were noted at delivery.
A dot ELISA was used to analyze the antibody response to varicella-zoster virus glycoproteins I, II, and III in leukemic and healthy children who either developed natural varicella or received the live attenuated varicella vaccine. Both groups of children showed an antibody response to these viral glycoproteins. The antibody response to all three glycoproteins showed excellent persistence over the 3-year period of study. None of the glycoproteins provoked an antibody response that could be shown to correlate with protection from breakthrough varicella after household exposure to chickenpox or from zoster in leukemic vaccinees.
Aztreonam is the first monocyclic beta-lactam antibiotic released for clinical use. Extensive toxicity and safety data for aztreonam in animals, healthy volunteers and adult patients have been accumulated previously; recently these studies have been extended to children. Overall the incidence of adverse clinical reactions caused by aztreonam is similar to or lower than that caused by comparison drugs. There is no evidence that aztreonam causes significant ototoxicity or nephrotoxicity; biochemical and hematologic abnormalities are rarely significant. Compared with the broad spectrum cephalosporins, aztreonam causes less disruption of normal gastrointestinal flora and consequently a lower incidence of diarrhea. Aztreonam does not displace bilirubin from albumin and penetrates readily into cerebrospinal fluid. Because of negligible immunologic cross-reactivity with other beta-lactams, aztreonam has been safely administered to patients with IgE-mediated penicillin hypersensitivity. These data suggest that aztreonam should be safe and well-tolerated in infants and children with infections caused by susceptible Gram-negative bacteria.
Weanling CD-1 male rats were subjected to 100, 75, and 50% splenectomy. One week following splenectomy, animals received either a sham immunization with 0.1 ml NS or pneumococcal immunization with 0.1 ml of a polyvalent (23) vaccine. Eight weeks following surgery, all animals received an intraperitoneal inoculation with 10(6) Streptococcus pneumoniae Type 3 organisms and were observed for mortality. Significant differences in mortality were seen between sham and immunized animals undergoing 100 or 75% splenectomy, while in the 50% group a difference was noted which did not reach statistical significance (Mantel-Cox log rank test). Patients undergoing greater than 50% splenectomy may be afforded greater protection against overwhelming pneumococcal infections by immunization with pneumococcal vaccine.
The well documented increased susceptibility of the asplenic host to overwhelming sepsis by encapsulated organisms has led to three popular prophylactic measures in patients: 1) pneumococcal vaccination; 2) vaccination with oral penicillin prophylaxis; or 3) vaccination with penicillin use at the first sign of infection. An animal model (weanling CD-1 rats) was utilized to evaluate these prophylactic measures. One hundred sixty rats underwent splenectomy and were divided into four treatment groups: I) sham vaccination; II) pneumococcal vaccination; III) vaccination and IM penicillin 24 hours after intraperitoneal inoculation of 10(6) Streptococcus pneumoniae type III; IV) vaccination and IM penicillin starting 3 days before IP inoculation. Six days following the bacterial challenge survival rates by group were: I) 5%; II) 25%; III) 100%; IV) 100% (p less than 0.001 by phi 2 likelihood ratio). Mantel- Cox log rank analysis of survival curves yielded significant differences between all groups except III and IV (p less than 0.001). This study in weanling rats supports the use of penicillin in the asplenic host. Daily prophyactic penicillin or penicillin started at the first sign of infection appears to be equally effective. Randomized studies in humans would determine the best regimen.
A rabbit model was used to characterize the effects of high (Group II, 100 mg/kg) and low (Group III, 10 mg/kg) dose ibuprofen in modulating the hemodynamic and hematologic manifestations of group B streptococcal shock. Short-term survival was significantly increased with ibuprofen pretreatment. Ibuprofen failed to prevent GBS-induced shock, although shock was favorably modified in a dose dependent manner. Likewise, GBS-induced increases in 6KPGF1a and TxB2 were not prevented but were modified in Group II at 120 min. However, neutropenia, thrombocytopenia, and acidosis were not prevented by pretreatment with ibuprofen and may have been exacerbated. Thus, ibuprofen modifies but does not prevent GBS-induced hemodynamic and hematologic manifestation.
Twenty-nine adult patients with cystic fibrosis received 750 or 1,000 mg of ciprofloxacin orally every 12 hours for two weeks. Pharmacokinetic data were collected on Days 1, 7, and 14. Pharmacokinetic analyses revealed minor differences between the dosage regimens, and results were similar on the first, seventh, and last day of therapy. Means for peak serum concentration (3.1 to 5.0 micrograms/ml), elimination half-life (4.8 to 5.3 hours), area under the time-concentration curve, and serum clearance (36.8 to 44.5 liter/hour) were similar to previously reported results for patients without cystic fibrosis. Sputum concentrations approximated serum values.
Twenty-nine adult patients with cystic fibrosis who had chronic bronchopulmonary infection were randomly assigned to receive 750 or 1,000 mg of oral ciprofloxacin every 12 hours for two weeks. Assessments for efficacy and safety were made on treatment Days 7 and 14 and one week following completion of therapy, and pharmacokinetic data were collected on Days 1, 7, and 14. Fifteen of 28 evaluable patients showed clinical improvement, and none had clinical deterioration. The higher dosage of ciprofloxacin did not enhance the clinical response. Statistically significant, stepwise changes in clinical scores, pulmonary function, and sputum concentrations of Pseudomonas aeruginosa and Staphylococcus aureus were noted, but regression toward initial values occurred by one week after treatment. Although all P. aeruginosa isolates were initially inhibited by 2 mg/liter of ciprofloxacin or less, 45 and 35 percent of isolates were resistant after 14 days of therapy and one week later, respectively. Outpatient oral ciprofloxacin therapy was commonly associated with clinical improvement in adult patients with cystic fibrosis who have chronic bronchopulmonary infection, regardless of the emergence of resistant P. aeruginosa, and adverse reactions were infrequent. Further studies must delineate the long-term consequences of the frequent emergence of bacterial resistance.
We studied the aggregatory characteristics of human polymorphonuclear leukocytes (PMNs) in response to heat-inactivated group B streptococcus. PMNs suspended in physiologic salt solution do not aggregate to heat-inactivated group B streptococcus (GBS) unless the GBS is previously opsonized in autologous plasma. The aggregating activity of both opsonized GBS and activated plasma are reduced if the plasma is decomplemented before incubation with GBS. Pretreatment of PMNs with pronase inhibited opsonized GBS-induced aggregation, suggesting aggregation via cell membrane receptors for opsonic fragments of C3. Pronase pretreatment had no significant effect on aggregation induced by activated plasma or arachidonic acid. Unlike PMNs in physiologic salt solution, PMNs suspended in plasma aggregate when stimulated by unopsonized GBS. GBS aggregates PMNs via complement cascade activation, opsonization, and interaction with cell membrane receptors to stimulate cellular mechanisms resulting in PMN aggregation.
Evidence suggests that part of the pathophysiologic response seen in group B streptococcal (GBS) sepsis may be due to polymorphonuclear leukocyte (PMN) activation. Indomethacin (INDO), which inhibits eicosanoid metabolism, attenuates the pathophysiologic response stimulated by GBS, possibly due to inhibition of PMN aggregation. We examined the capability of two eicosanoid metabolism inhibitors, INDO and nordihydroguaiaretic acid (NDGA), to inhibit PMN aggregation induced by heat-inactivated opsonized GBS and GBS-activated plasma. Opsonized GBS-induced PMN aggregation was inhibited by INDO (50-500 microM) and NDGA (1-100 microM). Over similar concentration ranges, INDO and NDGA had no significant effect on PMN aggregation induced by GBS-activated plasma. PMNs in plasma aggregate in response to unopsonized GBS. The stimuli for aggregation are opsonized GBS and GBS-activated plasma. INDO (50-500 microM) was unable to inhibit aggregation under this condition. Over the same concentration range in which INDO inhibited opsonized GBS-induced PMN aggregation, INDO was unable to inhibit opsonized GBS-induced superoxide production in PMNs. NDGA was examined but was found to interfere with the assay. The above evidence suggests PMN aggregation via eicosanoid metabolism may play a role in GBS-induced sepsis, which may be attenuated by agents such as INDO and NDGA.
Mean peak enoxacin serum concentrations in nonfasted CF-1 mice following a single 50, 100, or 200 mg/kg oral dose were 2.0, 4.0 and 11.4 mg/l, respectively, with proportional increases in area under the serum concentration curves. Oral enoxacin was significantly more effective than tobramycin or dicloxacillin in experimental Pseudomonas aeruginosa and Staphylococcus aureus infections respectively. Enoxacin was as effective as tobramycin against P. cepacia and Escherichia coli infections. Enoxacin may be useful as an oral antimicrobial for the treatment of selected systemic bacterial infections.