Successful treatment of epiglottitis with two doses of ceftriaxone.

Epiglottitis in childhood is caused by Haemophilus influenzae type b. The usual antibiotic treatment at the Royal Children's Hospital, Parkville, Victoria is a five day course of chloramphenicol. Increasingly, third generation cephalosporins are being used to treat invasive H influenzae type b infections and preliminary data suggest that they can be used successfully for epiglottitis. In a prospective, randomised trial, the efficacy of a short course (two days) of ceftriaxone was compared with that of five days of chloramphenicol for the treatment of epiglottitis. The ability of these treatment regimens to eradicate H influenzae type b from the throat was also studied. Fifty five children were enrolled over an 18 month period. Epiglottitis was diagnosed clinically and confirmed on inspection of the epiglottis at direct laryngoscopy. Fifty three (96%) of 55 patients had H influenzae type b detected from at least one site: 44/52 (85%) from blood cultures, 41/47 (87%) from throat swab, and 6/8 (75%) as H influenzae type b urinary antigen. Children were randomised to receive either ceftriaxone 100 mg/kg intravenously followed by a single dose of 50 mg/kg 24 hours later (28 patients), or chloramphenicol 40 mg/kg intravenously, then 25 mg/kg eight hourly for five days, intravenously then by mouth (27 patients). All household contacts and patients receiving chloramphenicol received rifampicin 20 mg/kg daily for four days. Index patients randomised to ceftriaxone were not treated with rifampicin. There was no significant difference in outcome between the two groups with respect to the mean duration of fever, the duration of intubation, or the length of hospital admission. The proportion of patients colonised with H influenzae type b four weeks after discharge was not significantly different between the two groups: ceftriaxone 5/22 (23%) versus chloramphenicol and rifampicin 3/23 (13%). A short course of ceftriaxone was successful in treating all patients with no significant side effects and no relapses. A short course of ceftriaxone is a safe, efficacious, and economic alternative to the standard treatment in children with epiglottitis.     

Successful treatment of epiglottitis with two doses of ceftriaxone

Epiglottitis in childhood is caused by Haemophilus influenzae type b. The usual antibiotic treatment at the Royal Children's Hospital, Parkville, Victoria is a five day course of chloramphenicol. Increasingly, third generation cephalosporins are being used to treat invasive H influenzae type b infections and preliminary data suggest that they can be used successfully for epiglottitis. In a prospective, randomised trial, the efficacy of a short course (two days) of ceftriaxone was compared with that of five days of chloramphenicol for the treatment of epiglottitis. The ability of these treatment regimens to eradicate H influenzae type b from the throat was also studied. Fifty five children were enrolled over an 18 month period. Epiglottitis was diagnosed clinically and confirmed on inspection of the epiglottis at direct laryngoscopy. Fifty three (96%) of 55 patients had H influenzae type b detected from at least one site: 44/52 (85%) from blood cultures, 41/47 (87%) from throat swab, and 6/8 (75%) as H influenzae type b urinary antigen. Children were randomised to receive either ceftriaxone 100 mg/kg intravenously followed by a single dose of 50 mg/kg 24 hours later (28 patients), or chloramphenicol 40 mg/kg intravenously, then 25 mg/kg eight hourly for five days, intravenously then by mouth (27 patients). All household contacts and patients receiving chloramphenicol received rifampicin 20 mg/kg daily for four days. Index patients randomised to ceftriaxone were not treated with rifampicin. There was no significant difference in outcome between the two groups with respect to the mean duration of fever, the duration of intubation, or the length of hospital admission. The proportion of patients colonised with H influenzae type b four weeks after discharge was not significantly different between the two groups: ceftriaxone 5/22 (23%) versus chloramphenicol and rifampicin 3/23 (13%). A short course of ceftriaxone was successful in treating all patients with no significant side effects and no relapses. A short course of ceftriaxone is a safe, efficacious, and economic alternative to the standard treatment in children with epiglottitis.     

A prospective randomized comparison of cefotaxime vs ampicillin and chloramphenicol for bacterial meningitis in children

Fifty children with bacterial meningitis were prospectively randomized to receive cefotaxime (50 mg/kg/dose every 6 hours) or ampicillin and chloramphenicol in standard doses. Twenty-three patients received cefotaxime and 27 received standard therapy. Bacterial isolates included: Haemophilus influenzae (29), Streptococcus pneumoniae (eight), Neisseria meningitidis (eight), group B streptococci (three), and Salmonella enteritidis (two). Ten (34%) of the H. influenzae isolates were resistant to ampicillin, nine on the basis of beta-lactamase production. All strains were susceptible to cefotaxime. Clinical cure rates for the cefotaxime (100%) and standard therapy (96%) groups were similar; survival without detectable sequelae was similar, at 78% and 77%, respectively. The duration of therapy, 11.1 +/- 2.4 days (range 10 to 21 days) vs 11.9 +/- 3.9 days (range 10 to 21 days), and days to defervescence, 4.7 +/- 2.6 days (range 1 to 14 days) vs 5.6 +/- 2.9 days (range 2 to 17 days), were similar in the cefotaxime and standard therapy groups, respectively. No adverse drug reactions or side effects were noted in either group. Cefotaxime was found to be as safe and effective as standard therapy for the treatment of bacterial meningitis in children.     

Cefuroxime therapy for bacteremic soft-tissue infections in children

Although it is used extensively in Europe, there is a limited amount of published data concerning pediatric clinical experience with cefuroxime in the United States. Thirty-six children, ranging from 3.5 to 57 months of age, received intravenous cefuroxime (75 mg/kg/day in three divided doses) for soft-tissue infections of the face or epiglottis. Infections treated included preseptal (19 patients) and buccal (13 patients) cellulitis and epiglottitis (four patients). Blood cultures were positive in 22 patients, yielding Haemophilus influenzae type b in 17 (four were beta-lactamase-positive), Streptococcus pneumoniae in four; and beta-lactamase-positive, nontypable H influenzae in one. An additional five patients with buccal cellulitis had negative blood cultures but H influenzae type b antigenuria. A satisfactory clinical response was noted in all patients, and repeated blood cultures performed in initially bacteremic patients were sterile. Cefuroxime therapy was well tolerated, and abnormal laboratory results were infrequent, except for absolute granulocytopenia (granulocytes, less than 1,500/cu mm), which occurred in six patients but could not be ascribed to a drug effect because of the uncontrolled design of our study. Treatment with cefuroxime appears to be a safe and effective therapy for pediatric soft-tissue infections due to H influenzae and S pneumoniae.     

Cefotaxime monotherapy in bacterial meningitis in childhood

Bacterial meningitis in 20 children was treated with cefotaxime. 17 children received this antibiotic throughout the disease as monotherapy, three were changed to Penicillin G (2) or ampicillin (1), after sensitivity of the pathogen was known, although cefotaxime had been effective. All bacterial isolates were highly susceptible to cefotaxime. All CSF cultures were sterile at second tap, performed 24 to 48 hrs after therapy was started. Cefotaxime and desacetyl-cefotaxime concentrations in CSF, measured by HPLC in 9 patients were in the range of 4 to 34 (average 17.6) mg/l and 2.1 to 82 (average: 15.1) mg/l, representing a CSF-serum ratio of 8 to 74% (average 45.6%) for cefotaxime and 25 to 151% (average: 73.7%) for desacetyl-cefotaxime. Clinical outcome was favourable in 17 patients. There were one death and late neurological deficits in three. Cefotaxime monotherapy is recommended instead of standard therapy with chloramphenicol and/or ampicillin because of superior antibacterial activity, lower toxicity and lesser side-effects for primary meningitis in children caused by N. meningitides, S. pneumoniae, or H. influenzae type b.     

Moxalactam therapy of Haemophilus influenzae type b meningitis in children

Thirty-four children with Haemophilus influenzae type b meningitis were given prospectively either moxalactam (200 mg/kg/day) or ampicillin (400 mg/kg/day) plus chloramphenicol (75 mg/kg/day). One patient in each group died. The mean duration of fever, clinical response, sequential cerebrospinal fluid findings, and incidence of neurologic sequelae were similar between groups. Moxalactam cerebrospinal fluid bioactivity was significantly greater than that of ampicillin or chloramphenicol throughout therapy. Neutropenia, liver enzyme abnormalities, and diarrhea were not significantly different. In eight of 11 patients given moxalactam (versus one of 14 controls) there was complete elimination of gram-negative aerobic flora in the stools by day 10 (P = 0.002); however, none acquired Clostridium difficile. Moxalactam in effective therapy for H. influenzae type b meningitis.     

Acute epiglottitis in children and adults in Sweden 1981-3.

In a retrospective study of the incidence of acute epiglottitis in Sweden, 485 children and 356 adults fulfilled the following criteria: (a) red and swollen epiglottis visualised at laryngoscopy; (b) stridor or difficulties in swallowing own saliva or water; and (c) temperature greater than or equal to 38 degrees C. The age specific incidence in children (0-14 years) was 10 and in adults (greater than or equal to 15 years) 1.8/100,000/year. These incidence rates were higher than the incidence of Haemophilus influenzae meningitis in the same population. Blood cultures were obtained from 290 children (60%) and 185 adults (52%). H influenzae was isolated from 267 blood cultures (92%) from children and 98 blood cultures from adults (53%). Other organisms were isolated from six adults (3%). An artificial airway was established in 352 children (73%) and in 68 adults (19%); the remainder were treated conservatively. Six children and two adults died. Sweden has a high incidence of acute epiglottitis in children and the disease also occurs in adults. The importance of H influenzae in the aetiology of epiglottitis in all age groups is confirmed, but in adults many cases occur without septicaemia. The mortality is currently very low.     

流感嗜血杆菌患儿分离株的血清分型和耐药模式研究

目的　了解流感嗜血杆菌患儿分离株的血清分型和体外耐药模式。方法　对本院2 0 0 1年 8月～ 2 0 0 2年 7月经apiNH卡鉴定的 2 4 7株流感嗜血杆菌 ,用玻片凝集法进行血清分型 ,用Kirby Bauer法检测其对 13种抗生素的敏感性 ,并用E test法检测氨苄西林的最低抑菌浓度。用头孢硝噻酚法检测 β内酰胺酶。 结果　不可分型流感嗜血杆菌 15 3株 ,占细菌总数 6 1 9% ,可分型菌株94株 ,占 38 1% ;可分型株在男女患儿中的分离率分别为 4 3 2 % (70 / 16 2 )和 2 8 2 % (2 4 / 85 ) ,差异有显著性 (χ2 =3 95 ,P <0 0 5 )。可分型菌株中d型构成比达 90 4 % ,b型仅 1 1%。 4 1株菌株(16 6 % )产生 β内酰胺酶。 2 33株菌株成功完成药敏试验 ,结果显示 :85 4 %的菌株对氨苄西林敏感 ,对头孢克洛、头孢噻肟、头孢曲松、亚胺培南、利福平、克拉霉素和氯霉素的敏感率分别高达98 7%、99 6 %、99 6 %、99 6 %、98 7%、91 0 %和 90 6 %。所有的菌株均对氨苄西林 /舒巴坦、阿莫西林 /克拉维酸和氧氟沙星敏感。菌株对甲氧苄啶 磺胺甲基异恶唑的耐药率最高 ,达 4 5 9%。可分型株对氨苄西林和甲氧苄啶 磺胺甲基异恶唑的耐药率显著高于不可分型株。β内酰胺酶阳性菌多重耐药率显著高于阴性菌 (χc2 =14 6 8,P <0 0 0 1     

Treatment of ampicillin-resistant Haemophilus influenzae in soft tissue infections with high doses of ampicillin.

Six soft tissue infections (three epiglottitis, one cellulitis, one pneumonia, and one arthritis) with ampicillin-resistant Haemophilus influenzae were treated initially with high doses of ampicillin (200 to 400 mg/kg/day intravenously) alone and had good clinical responses. All had documented bacteremia with H. influenzae. One child was treated only with ampicillin; treatment in the remainder was changed to oral therapy with other antibiotics to facilitate discharge. There was no recurrence of disease. Disc diffusion studies done on clinical isolates of both resistant and sensitive organisms indicate a break point at which the resistant organism shows progressive sensitivity to increasingly higher concentrations of ampicillin.     

Detection and quantitation of bacteremia in childhood.

Quantitative blood cultures were sought in 383 children, from whom routine blood cultures were obtained because of fever, by direct plating of 10 and 100 microliter blood onto solidified media. There were 14 positive cultures from 12 patients. These were 7 Hemophilus influenzae type b, 5 Streptococcus penumoniae, and 2 Staphylococcus aureus. The direct-plating technique permitted more rapid identification of positive cultures, and detected three episodes not identified by routine broth culture. Bacterial counts ranged from 20 to greater than 10(4) bacteria/ml blood. In the three cases of H. influenzae type b meningitis, bacteremia exceeded 10(3)/ml. Among nine patients in whom bacteremia was unassociated with meningitis, (bacteremia without evident localized disease 5, pneumonia 2, epiglottitis 1, peritonitis 1), bacteremia was less than 10(3)/ml. This technique may aid detection of bacteremia and help identify those children at highest risk for developing septic complications, such as meningitis.     

Haemophilus influenzae type b meningitis resistant to ampicillin and chloramphenicol.

We report two cases of meningitis due to Haemophilus influenzae type b resistant to ampicillin and chloramphenicol. In one child the meningitis was preceded by pneumonia and pleural effusion. Both children responded to treatment with cefotaxime.     

Treatment of Haemophilus influenzae type B epiglottitis.

During 1969-1977, 48 children with blood cultures proved positive for Haemophilus influenzae type B epiglottitis were evaluated and treated. The fatality rate was 2%; one child died and another developed irreversible hypoxic brain damage. Ninety-five percent of the children were intubated and none required tracheostomy. The endotracheal tubes remained in place for 3.3 +/- 1.5 days. Short-term parenteral antimicrobial therapy, 4.0 +/- 1.4 days, was sufficient to eradicate bacteremia and prevent metastatic infectious foci. This report demonstrates the excellent results achieved in the treatment of epiglottitis with brief intubation and parenteral antimicrobial therapy.     

杭州市上呼吸道感染患儿分离的流感嗜血杆菌分离株的血清分型及其对氨苄西林的耐药性分析

目的：了解从呼吸道感染患儿分离出的流感嗜血杆菌血清分型及其对氨苄西林耐药性。方法：流感嗜血杆菌的鉴定采用V因子,X因子和V+X因子试验,血清分型采用玻片凝集法,β内酰胺酶检测采用头孢硝噻酚法,药敏试验采用纸片扩散法和E-test法。结果：2006年12月至2007年7月共分离到的流感嗜血杆菌152株,其中男性患儿108株,占71.0%,女性患儿44株,占29.0%。血清分型显示不可分型流感嗜血杆菌148株,占97.4%,可分型流感嗜血杆菌4株,占2.6%;可分型菌株中,a,d,e,f型各1株,无b,c型菌株发现。34株菌株(22.4%) 产生β内酰胺酶。152株流感嗜血杆菌中,全部菌株成功完成药敏试验,113株菌株(74.3%)对氨苄西林敏感;141株菌株用E-test法检验了最低抑菌浓度（MIC）,氨苄西林MIC50为0.25 μg/mL,MIC90为12 μg/mL。结论：该研究中流感嗜血杆菌分离株以不可分型菌株占绝对优势,74.3%流感嗜血杆菌对氨苄西林敏感。［中国当代儿科杂志,2009,11（3）：217-220］     

Epidemiology of invasive Haemophilus influenzae type b disease among children in Finland before vaccination with Haemophilus influenzae type b conjugate vaccine

On the basis of intensified surveillance in Finland we report the epidemiology of invasive Haemophilus influenzae type b disease based on 333 consecutive culture-proved cases recorded during 1985 and 1986. The annual incidence rate among children younger than 5 years of age was 52/100,000; 46% of patients had meningitis, 29% had epiglottitis and 25% had other forms of invasive disease. The median age of patients was 27 months, with 45% younger than 2 years of age. Meningitis and epiglottitis were found more often among boys than among girls, whereas the opposite was found among patients with other types of invasive disease (P = 0.015). Among the latter 68% of children with pneumonia or septicemia were 2 years or older compared with 32% of patients with arthritis, cellulitis or pyelonephritis (P = 0.009). These background data are essential for correct interpretation and application of results from trials with H. influenzae type b conjugate vaccines that are currently ongoing in Finland.     

Haemophilus influenzae type b bacteremia in older children.

Haemophilus influenzae type b (HIB) is a well-recognized cause of serious infection in infants and toddlers. However, little information exists regarding HIB infections in older children. This report describes serious HIB infections in 23 children (eight immunocompromised; 15 immunocompetent) older than 59 months of age. Data were collected over an 11-year period. The mean age of the children was 7.6 years (range, 5-15 years), and 14 were male. While three of the eight immunocompromised children had HIB pneumonia, none of the immunocompetent group had this diagnosis. Eleven of the 15 immunocompetent children had epiglottitis or meningitis. HIB bacteremia without focal infection occurred in four children, two immunocompromised and two immunocompetent. This study supports the recommendation of empiric HIB antibiotic therapy for children up to 12 years of age who have serious infections. Antibiotics effective against HIB should be included in the presumptive antibiotic therapy of seriously ill immunocompromised children, regardless of age.     

Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.     

Antibiotic Susceptibility of Type b Haemophilus influenzae and Streptococcus pneumoniae, and Antibiotic Concentration in Cerebrospinal Fluid

Antibiotic susceptibilities of 38 type b Haemophilus influenzae and 28 Streptococcus pneumoniae strains isolated from cerebrospinal fluid, blood and other specimens between 1973 and 1988 were studied. Minimal inhibitory concentrations (MICs) of ampicillin against 10 β-lactamase positive and 28 negative H. influenzae isolates were 32–64 and 0.25 μg/ml, respectively. The MIC of chloramphenicol against one of the β-lactamase positive H. influenzae strains was 8 but MICs against the rest of the organisms were 0.5–1 μg/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all H. influenzae strains were 0.016, 0.008 and 0.5 μg/ml, respectively. No S. pneumoniae isolates were resistant to penicillin G and MICs of this drug were 0.016–0.032 μg/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all S. pneumoniae strains were 0.016–0.032, 0.016–0.032 and 0.032–0.063 μg/ml, respectively. MICs of chloramphenicol against 15, 4 and 9 of S. pneumoniae isolates were 2, 8 and 16 μg/ml, respectively. Antibiotic concentrations in the cerebrospinal fluid of patients with bacterial meningitis after intravenous administration of ampicillin (50–70 mg/kgx4/day), penicillin G (31–63 mg/kgx4/day), cefotaxime (50 mg/kgx4/day) and chloramphenicol (25 mg/kgx4/day) were 4.70±1.83 (n=11), 0.57±0.32 (n=7), 4.97±2.60 (n=9) and 8.52±3.54 μg/ml (n=3), respectively. The initial choice of antibiotics in older children with bacterial meningitis is a combination of ampicillin (75 mg/kgx4/day) and cefotaxime (50 mg/kgx4/day) to cover ampicillin-resistant H. influenzae, S. pneumoniae , and Listeria monocytogenes in Japan. These antibiotics should be changed according to the causative organisms and their antibiotic susceptibilities.     

Antimicrobial susceptibility of respiratory Haemophilus influenzae strains isolated from pediatric respiratory tract infections

BACKGROUND: Haemophilus influenzae (H. influenzae) is the most frequent bacterial pathogen of respiratory tract infections in children. Detection of antimicrobial susceptibility of H. influenzae is necessary for institution of appropriate antibiotic treatments. METHODS: A total of 281 strains of H. influenzae isolated from sputum samples of 281 pediatric patients with respiratory tract infections were recruited for study. Antibiotic susceptibility was determined by assessing minimum inhibitory concentrations (MIC) of antimicrobial agents. MIC were measured by utility of Agar dilution susceptibility test. RESULTS: Of the total, 38 (13.5%) strains produced beta-lactamase (BLP), 56 (19.9%) strains were beta-lactamase non-producing, ampicillin resistant (BLNAR). The overall resistant proportion to ampicillin was 33.4%. The data indicated that sulbactam/ampicillin, cefotaxime, ceftriaxone and cefditoren are effective against BLP strains. In addition, a high prevalence of BLNAR H. influenzae strains was identified, with an overall isolation rate of 19.9%. Those strains mainly demonstrated intermediate level to ampicillin (ampicillin-MIC 相似文献   

Protective effect of subinhibitory polymyxin B alone and in combination with ampicillin for overwhelming Haemophilus influenzae type B infection in the infant rat: evidence for in vivo and in vitro release of free endotoxin after ampicillin treatment

The potential endotoxin modifying effects of subinhibitory doses of polymyxin B were evaluated in an animal model of overwhelming septicemia. Five to six day old Sprague-Dawley rats were infected intraperitoneally with 10(6)-10(7) cfu of Haemophilus influenzae type b. At 12 h after infection, at which time mortality was 18%, subinhibitory doses of polymyxin b (0.0125 mg/kg X 3 q 3 h) either alone or in combination with 500 mg/kg ampicillin significantly increased survival at 17 and 20 h (p = 0.009, 0.01 and p = 0.003, 0.01) compared to animals treated with 0.5 mg/kg of ampicillin alone. Prolonged survival at 36 h (p = 0.009) was seen in animals receiving both ampicillin and low dose polymyxin compared to either ampicillin dose alone. Ampicillin significantly reduced the number of bacteria in blood of survivors (p less than 0.023 at 30 min) compared to untreated animals but increased the activity of free endotoxin at 30 min compared to controls (p = 0.006). In vitro endotoxin release from H. influenzae type b increased 5-fold after addition of 100 micrograms/ml of ampicillin, whereas a six-fold reduction in endotoxin activity was measured after the addition of 7 micrograms/ml of polymyxin B. Subinhibitory doses of polymyxin B modulate the ethal effects of overwhelming H. influenzae type b infection in infant rats and might be beneficial as adjunct treatment in gram-negative septicemia.     

Pyogenic meningitis in hospitalized children in Kelantan, Malaysia.

A 2.5-year retrospective study of pyogenic meningitis in hospitalized children in Kelantan was carried out with regard to aetiology, clinical features, investigation, treatment and outcome. There were 58 children with 43 cases (74.1%) occurring below the age of 1 year. Frequent presenting symptoms included fever (98.3%), fits (77.6%), anorexia (39.7%), vomiting (34.5%) and drowsiness (12.1%). On admission, 37 (63.7%) had neck stiffness, 10 (17.2%) had Kernig's sign and 32 (55.2%) had coma. CSF cultures were positive for Haemophilus influenzae in 29 (50%), Streptococcus pneumonia in 13 (22.4%) and Neisseria meningitidis in 3 (5.2%). The antibiotic sensitivity profiles showed that the three main organisms were 100% sensitive to Chloramphenicol, Streptococcus pneumoniae was 100% sensitive to penicillin, Neisseria meningitidis was 100% sensitive to penicillin and ampicillin, and Haemophilus influenzae was 90% sensitive to penicillin and ampicillin. The total hospital mortality was 18.9%. All but two of the eleven deaths occurred in children younger than 1 year. Nineteen of the 35 (54.3%) survivors attended for at least one follow-up after discharge from hospital. Of these 19 children, 47.4% had neurological sequelae.