Bacterial meningitis following introduction of Hib conjugate vaccine in northern Uganda

BACKGROUND: St Mary's Hospital, Lacor is in Gulu district in northern Uganda. Owing to conflict and insurgency, the majority of the hospital population live in internally displaced people's camps. There is ongoing public health surveillance of paediatric bacterial meningitis by the hospital. Before the introduction of Haemophilus influenza type b (Hib) conjugate vaccine in June 2002, Hib was the leading cause of bacterial meningitis in the area. METHODS: All patients with suspected bacterial meningitis between April 2003 and August 2006 were recruited. Meningitis was confirmed by isolation of bacteria. RESULTS: During the study period, 4986 cases of suspected bacterial meningitis were identified, 395 of whom had purulent cerebrospinal fluid (CSF). A culture was obtained from 259 (65%): Streptococcus pneumoniae 132 (51%), H. influenzae 22 (8.5%), salmonella spp 85 (32.8%), Neisseria meningitidis 9 (3.5%) and others 11 (4.2%). Over the surveillance period, there was a remarkable decline in the prevalence of H. influenza meningitis to only three cases or fewer per year compared with 42 in 2001. The minimum incidence of Streptococcus pneumoniae meningitis among children under 5 years of age was 33.7/100,000 of population and it was more prevalent during the dry season. The minimum incidence of non-typhoidal salmonella spp meningitis was 22.7/100,000, making it the second most common cause of paediatric bacterial meningitis with a case fatality rate of 18.2%. CONCLUSION: Hib conjugate vaccine delivered through the national immunisation programme is very effective in reducing Hib meningitis in children under 5 years of age. Continued laboratory-based surveillance of bacterial meningitis in Africa is needed to assess the effectiveness of vaccination programmes and detect other vaccine-preventable pathogens.     

Assessment of a commonly available latex particle agglutination test in rapid, bacteriologic cerebrospinal fluid diagnosis

36 cerebrospinal fluid specimens (CSF) from patients with bacterial meningitis were tested for the presence of bacterial antigens with the "Slidex Meningite Kit" (Bio Merieux). This kit has latex particles coated with antibodies against hemophilus influenzae type B (Hib) streptococcus pneumoniae (SP) and neisseria meningitidis (NM) group A and C. With the LAT we could detect the bacterial antigens in 84% of bacterial meningitis cases, 23 of the 27 of Hib meningitis (85.2%), all of the 6 cases of SP meningitis (100%) and two of the three NM meningitis cases. The test is handicapped by the fact, that there is no antiserum against NM sero-group B, the main cause of NM meningitis in Austria. There were no false positive results with the LAT. False negative results were obtained in 19.2% of Hib and in one case of NM. Even under sufficient antibiotic therapy and with negative culture we could detect 9 Hib- and 1 NM-cases during the first 12-48 hours of therapy with this method. The LAT-Kit is a useful addition to standard methods of CSF examinations in bacterial meningitis. With the LAT a rapid bacteriological diagnosis is possible within 15 minutes. The Kit is also able to identify bacterial antigens even with negative culture and after initiation of antibiotic treatment.     

Evaluation of polymerase chain reaction (PCR) for diagnosing Haemophilus influenzae b meningitis

A polymerase chain reaction (PCR) for detecting Hib in cerebrospinal fluid (CSF) was evaluated and compared with culture and a latex agglutination test (LAT) in a hospital-based prospective surveillance. We studied 107 children aged from 1 month to 12 years with a clinical and CSF profile suggestive of acute bacterial meningitis. CSF culture was performed on blood-chocolate agar by standard technique, LAT by a commercially available kit (Wellcogen) and PCR using total DNA extracted from CSF samples. Of 107 children, 79% had received one or more doses of injectable antibiotics. Hib was detected by culture in 14 cases, by LAT in 23 and by PCR in 37. All CSF samples that reveal Hib by culture or LAT had a PCR positive for Hib (sensitivity 100%). PCR also detected 14 additional cases of Hib meningitis which were not detected by culture or LAT. We conclude that PCR is a sensitive and specific diagnostic tool that may be valuable in a population with high pre-hospital antibiotic usage.     

Absent or minimal cerebrospinal fluid abnormalities in Haemophilus influenzae meningitis

A case of Haemophilus influenzae type b (Hib) meningitis in which the diagnosis and treatment were delayed because of normal cerebrospinal fluid analysis is presented. A retrospective review was conducted at two children's hospitals to determine the frequency and clinical characteristics of patients with Hib meningitis whose spinal fluid had a normal total white blood cell count, normal chemistries, and negative Gram stain, but subsequent growth of Hib in culture. Of 379 cases of Hib meningitis, two had completely normal CSF, and two had CSF containing small numbers of polymorphonuclear cells as the sole abnormality. In three of the four cases, the duration of symptoms was less than 24 hours, and appropriate therapy was significantly delayed because of benign-appearing CSF. Normal CSF cell counts, chemistries, and Gram stain do not exclude the possibility of bacterial meningitis, and one should remain suspicious when a child has clinical findings suggesting meningitis.     

Impact of haemophilus influenzae type b conjugate vaccine in South Africa and Argentina

INTRODUCTION: Haemophilus influenzae type b (Hib) persists as a major cause of pediatric meningitis and pneumonia in developing countries in which Hib conjugate vaccines are not used. Demonstration of decreases in severe Hib disease after countries introduce Hib conjugate vaccine will help justify the resources necessary to purchase and provide the vaccine. Because surveillance for culture-confirmed Hib meningitis is not available in many countries, alternative means to measure the impact of Hib conjugate vaccine would be useful. METHODS: Laboratory records from the years before and after introduction of the Hib conjugate vaccine were reviewed at 4 hospitals, 2 in Argentina and 2 in South Africa. Potential indicators of bacterial meningitis including cerebrospinal fluid (CSF) culture, white blood cell count, appearance, protein and glucose were recorded. RESULTS: After introduction of Hib conjugate vaccine, culture-confirmed Hib meningitis declined significantly at 3 of 4 hospitals (2 in Argentina and 1 in South Africa). In the same 3 hospitals, there was a significant decline after vaccine introduction in some of the following CSF indicators of bacterial meningitis: proportion of CSF specimens with white blood cell count > or = 100 x 10(6)/L, 500 x 10(6)/L and 1,000 x 10(6)/L; glucose <40 mg/dL; protein >100 mg/dL; and turbid appearance. CONCLUSIONS: Culture-confirmed Hib meningitis declined at 3 of the 4 hospitals after Hib vaccine introduction. Surrogate indicators of bacterial meningitis also declined and might be useful measures of Hib conjugate vaccine impact at hospitals where capacity to culture Hib is not available.     

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.     

The Diagnostic and Predictive Value of Cerebrospinal Fluid Lactate in Children with Meningitis

ABSTRACT. One hundred and thirty-three children with suspected meningitis aged from 11 days to 16 years were investigated with routine cerebrospinal fluid (CSF) laboratory methods: microscopy of a Gram-stained smear, bacterial culture, determination of leukocytes, lactate, and the CSF/blood glucose ratio. On the basis of bacterial cultures and clinical course, the children were classified into three groups: bacterial meningitis (n=18), aseptic meningitis (n=28), and a control group (n=87). The main intention was to study the relation between current diagnostic methods and lactate. CSF lactate levels and cell counts, related significantly (p<0.01) better to the presence of bacterial meningitis than CSF/blood glucose ratios. Lactate levels exceed 2.4 mmol/l in all children with bacterial meningitis, but in none of the control group. Of 28 children with aseptic meningitis 3 had lactate in the range 2.5-2.7 mmol/l, while the others had values of 2.4 mmol/l or less. We consider CSF lactate to be the best predictor in the clinical decision to institute antibiotic treatment of children with suspected bacterial meningitis.     

Detection of antigenuria for diagnosis of invasive Haemophilus influenzae type b disease

BACKGROUND: Haemophilus influenzae type b (Hib) diseases are responsible for an estimated 400,000 childhood deaths, mostly in developing countries. OBJECTIVES: To determine the value of the Wellcogen quantitative latex agglutination test (LA) in urine for the diagnosis of Hib pneumonia and meningitis. METHODS: Healthy and sick children aged <5 y were enrolled in Dhaka Shishu (Children's) Hospital. Boiled and non-concentrated urine specimens underwent LA testing. In vaccinated subjects, urine was tested by LA at 24 h, 4-6 and 7-10 d after vaccination. RESULTS: Of 1302 enrolled cases, 201 were healthy (90 Hib vaccine recipients and 111 provided NP) and 1101 were sick with either pneumonia (n=974) or meningitis (n=127). Among the healthy children enrolled, 41 (41/111, 37%) were colonised with Hib and two (2/41, 5%) were positive by LA test. Hib antigenuria among the children who had received Hib vaccination was mainly detected only on day 1 (7/90, 8%) of vaccination. Among the sick children, LA test for Hib antigen was positive for all confirmed cases of Hib pneumonia (10) and meningitis (35). In contrast, none of the urine specimens from the cases with a known aetiology other than Hib (n=104) was positive. Quantitative analysis of antigenuria of sick children showed that it is positive at least up to 1:8 and 1:16 dilutions for pneumonia and meningitis, respectively, in contrast with or=1:8 dilutions. CONCLUSIONS: The Wellcogen LA test for Hib using boiled and non-concentrated urine is more sensitive than blood culture alone and is highly specific.     

The diagnostic and predictive value of cerebrospinal fluid lactate in children with meningitis. Its relation to current diagnostic methods

One hundred and thirty-three children with suspected meningitis aged from 11 days to 16 years were investigated with routine cerebrospinal fluid (CSF) laboratory methods: microscopy of a Gram-stained smear, bacterial culture, determination of leukocytes, lactate, and the CSF/blood glucose ratio. On the basis of bacterial cultures and clinical course, the children were classified into three groups: bacterial meningitis (n = 18), aseptic meningitis (n = 28), and a control group (n = 87). The main intention was to study the relation between current diagnostic methods and lactate. CSF lactate levels and cell counts, related significantly (p less than 0.01) better to the presence of bacterial meningitis than CSF/blood glucose ratios. Lactate levels exceed 2.4 mmol/l in all children with bacterial meningitis, but in none of the control group. Of 28 children with aseptic meningitis 3 had lactate in the range 2.5-2.7 mmol/l, while the others had values of 2.4 mmol/l or less. We consider CSF lactate to be the best predictor in the clinical decision to institute antibiotic treatment of children with suspected bacterial meningitis.     

Cerebrospinal fluid C-reactive protein in the laboratory diagnosis of bacterial meningitis

Samples of cerebrospinal fluid from 112 cases of suspected meningitis were tested for the presence of C-reactive protein (CRP), using a qualitative and quantitative slide test. Bacterial meningitis was confirmed in 34 patients, based on CSF and blood culture results, and/or elevated CSF white blood cell (WBC) count and typical biochemical profile. There were 8 patients with early onset, and 3 who had received prior antimicrobial therapy among the 5 neonates, 23 children, and 6 adults with bacterial meningitis. Organisms recovered from CSF, and/or blood, included Haemophilus influenzae 14, Streptococcus pneumoniae 9, Streptococcus group B-5, Staphylococcus aureus 2, E. coli 2 and Klebsiella pneumoniae 1. Slide test was positive for CRP in 33 cases, giving a sensitivity of 97% which compared favourably with elevated CSF protein 33%, decreased CFS glucose 64.7% CSF glucose/blood glucose less than 1/2, 85%, raised CSF WBC 38.2%, raised CSF PMN 61.7%, CSF culture positive 88.2%, and CSF gram-positive 82.5%. Slide test was positive for CRP in 1 of 78 CSF samples negative for bacterial meningitis, giving a specificity of 98%. It was concluded that testing of CSF for CRP is a simple, rapid and accurate method for the laboratory diagnosis of bacterial meningitis, which is particularly appropriate for areas lacking adequate laboratory facilities.     

Cerebrospinal Fluid C-Reactive Protein in the Laboratory Diagnosis of Bacterial Meningitis

ABSTRACT. Samples of cerebrospinal fluid from 112 cases of suspected meningitis were tested for the presence of C-reactive protein (CRP), using a qualitative and quantitative slide test. Bacterial meningitis was confirmed in 34 patients, based on CSF and blood culture results, and/or elevated CSF white blood cell (WBC) count and typical biochemical profile. There were 8 patients with early onset, and 3 who had received prior antimicrobial therapy among the 5 neonates, 23 children, and 6 adults with bacterial meningitis. Organisms recovered from CSF, and/or blood, included Haemohilus influenzae 14, Streptococcus pneumoniae 9, Streptococcus group B 5, Staphylococcus aureus 2, E. coli 2 and Klebsiella penumoniae 1. Slide test was positive for CRP in 33 cases, giving a sensitivity of 97 % which compared favourably with elevated CSF protein 33 %, decreased CFS glucose 64.7 % CSF glucose/blood glucose 相似文献   

Test characteristics and interpretation of cerebrospinal fluid gram stain in children

BACKGROUND: Few data exist regarding the test characteristics of cerebrospinal fluid (CSF) Gram stain among children at risk for bacterial meningitis, especially the rate of false positive Gram stain. METHODS: We conducted a retrospective cohort study of children seen in the emergency department of Children's Hospital Boston who had CSF obtained between December 1992 and September 2005. Patients who had ventricular shunts, as well as those who received antibiotics before CSF was obtained were excluded. Test characteristics of CSF Gram stain were assessed using CSF culture as the criterion standard. Patients were considered to have bacterial meningitis if there was either: (1) growth of a pathogen, or (2) growth of a possible pathogen noted on the final CSF culture report and the patient was treated with a course of parenteral antibiotics for 7 days or more without other indication. RESULTS: A total of 17,569 eligible CSF specimens were collected among 16,036 patients during the 13-year study period. The median age of study subjects was 74 days. Seventy CSF specimens (0.4%) had organisms detected on Gram stain. The overall sensitivity of Gram stain to detect bacterial meningitis was 67% [42 of 63; 95% confidence interval (CI): 54-78] with a positive predictive value of 60% (42 of 70; 95% CI: 48-71). Most patients without bacterial meningitis have negative Gram stain [specificity 99.9% (17,478 of 17,506; 95% CI: 99.8-99.9)] with a negative predictive value of 99.9 (17,478 of 17,499; 95% CI: 99.8-99.9). CONCLUSIONS: CSF Gram stain is appropriately used by physicians in risk stratification for the diagnosis and empiric treatment of bacterial meningitis in children. Although a positive Gram stain result greatly increases the likelihood of bacterial meningitis; the result may be because of contamination or misinterpretation in 40% of cases and should not, by itself, result in a full treatment course for bacterial meningitis.     

High pneumococcal DNA loads are associated with mortality in Malawian children with invasive pneumococcal disease

BACKGROUND: In bacteremia owing to Streptococcus pneumoniae, high bacterial counts at presentation have been shown to be predictive of the development of serious invasive disease. Using real-time PCR, we aimed to determine pneumococcal DNA loads in blood and CSF, and their relationship to cytokine concentrations, clinical presentation and outcome. METHODS: Children with confirmed meningitis (n = 82) or pneumonia (n = 13) were prospectively recruited, and blood and CSF samples taken for pneumococcal bacterial DNA loads and cytokine determination. RESULTS: At the time of admission, the median bacterial load in blood was 1.6 x 10 DNA copies/mL (range 0.00-1.54 x 10) and in CSF it was 5.77 x 10 DNA copies/mL (range 4.42 x 10 to 6.15 x 10). Median blood and CSF bacterial loads (log DNA copies/mL) were significantly higher in nonsurvivors than in survivors; blood (3.80 vs. 2.97, P = 0.003), CSF (8.17 vs. 7.50, P = 0.03). In HIV-infected children (n = 59), blood and CSF loads and plasma tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), IL-6 and IL-10 were all significantly higher in nonsurvivors than in survivors, but in HIV-uninfected children (n = 36) this difference was not significant. Blood bacterial loads and plasma cytokine concentrations were significantly associated, and were all significantly higher in children with meningitis than in those with pneumonia. In children with meningitis, median CSF cytokine concentrations were significantly higher than median plasma cytokine concentrations (P < 0.001) and CSF bacterial loads were significantly associated with CSF IL-1beta (P = 0.002) and IL-10 (P = 0.001) concentrations. CONCLUSIONS: Pneumococcal DNA loads are associated with plasma cytokine concentrations, and are higher in meningitis than in pneumonia. High blood and CSF pneumococcal DNA loads are associated with a fatal outcome.     

Pneumococcal meningitis in the newborn period in a prevaccination era: a 10-year experience at a tertiary intensive care unit

There are few data with respect to pneumococcal meningitis in neonates. Epidemiological aspects, clinical features and outcomes in newborn infants diagnosed with pneumococcal meningitis were evaluated in this study. Nineteen newborn infants in a neonatal intensive care unit diagnosed with culture-proven community-acquired bacterial meningitis between January 1999 and December 2008 were reviewed, and of them, eight patients were diagnosed as pneumococcal meningitis. Overall, among 10,186 hospitalized newborn infants, 132 community-acquired sepsis/meningitis cases (1.3%) were suspected, and blood cultures were performed in all, while cerebrospinal fluid (CSF) cultures could be performed in 124 cases. Rate of blood culture positivity was 45%. Nineteen (15.3%) of 124 were diagnosed as culture-proven community-acquired bacterial meningitis, which was confirmed by CSF growth. Eight (42.1%) of 19 had pneumococcal meningitis. In pneumococcal cases, abundant Gram-positive diplococci were seen on CSF smear and Streptococcus pneumoniae was isolated from CSF cultures. All isolates were susceptible to penicillin and third-generation cephalosporins. Irritability (n: 7), poor sucking (n: 7) and fever (n: 6) were the principal findings on the initial physical examination. Of all patients with pneumococcal meningitis, four were initially given cefotaxime plus amikacin treatment, and the remaining four were initially given cefotaxime plus ampicillin plus vancomycin. Antibiotic treatment in two patients was revised during their clinical course. Additionally, in three patients, vancomycin and ampicillin was discontinued on the third day when antibiogram of CSF cultures revealed penicillin sensitivity. Overall, mortality in pneumococcal meningitis was 50%. In the surviving patients, two had epilepsy, one sensorineural hearing loss, and two mental-motor retardation. Pneumococcal meningitis was the leading cause of community-acquired neonatal meningitis in our patients. Immunization against pneumococcal disease in developing countries would be beneficial for public health and for newborn infants.     

Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden

BACKGROUND: Streptococcus pneumoniae is the leading cause of childhood pneumonia and meningitis worldwide. Isolation of this organism, however, is uncommon in resource-poor countries, in part because of extensive use of prior antibiotics. A rapid, highly sensitive immunochromatographic test (ICT) for S. pneumoniae was evaluated for the diagnosis of meningitis. METHODS: Cerebrospinal fluid (CSF) from 450 children with suspected meningitis was tested with ICT, and results were compared with CSF culture, latex agglutination test (LAT) and/or polymerase chain reaction (PCR). Serial CSF specimens from 11 patients were also evaluated for duration of positive results during effective antimicrobial therapy. FINDINGS: All 122 cases of pyogenic pneumococcal meningitis positive either by culture (N = 87) or PCR (N = 35) were positive by ICT, yielding 100% (122 of 122) sensitivity. All purulent CSF specimens from patients with meningitis caused by other bacteria by culture (N = 149) or by LAT (N = 48) or those negative by culture, LAT and LytA and thus of unknown etiology (N = 20), and normal CSF specimens (N = 104) were negative by ICT. Thus the specificity of ICT also was 100% (321 of 321), although negativity of ICT was not confirmed by PCR, if it was positive for other organisms either by culture or LAT. Serotyping of S. pneumoniae strains revealed 28 different serotypes, indicating that outcome of ICT are independent of diverse capsular serotype of pneumococcus. Antigen was detected by ICT for at least 10 days after presentation, and 1 was still positive on day 20, which was longer than for either LAT or PCR. INTERPRETATION: ICT for pneumococcal antigen in CSF is 100% sensitive and specific in diagnosing pyogenic pneumococcal meningitis and can detect approximately 30% more pneumococcal meningitis cases than with culture alone. The simplicity of the test procedure and the longevity of CSF antigen detection suggest the potential utility of ICT to estimate the true burden of pneumococcal disease, as for Haemophilus influenzae type b using data from meningitis, and to guide selection of appropriate antibiotic treatment, especially in resource-poor countries with widespread prehospital antimicrobial use.     

Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989-1992

Children aged 1-59 months admitted to Goroka Base Hospital with signs suggestive of meningitis were recruited to determine what proportion of such children have clinical or bacterial meningitis and to investigate the bacterial aetiology. A laboratory classification of definite, probable, possible, indeterminate and no meningitis was established. Thirty per cent of 697 children had a final clinical diagnosis of meningitis, 12% had culture-proven bacterial meningitis (case fatality rate 34%) and 10% had probable or possible meningitis. Inability to feed, vomiting, drowsiness, "staring eyes" and haemoglobin < 9 g/dl in addition to the classical signs of meningitis were associated with increased mortality. Isolates from cerebrospinal fluid were 62 pneumococci, 22 Haemophilus influenzae type b (Hib) and one Neisseria meningitidis. Including blood culture-proven and antigen-proven Hib disease, Hib and pneumococci accounted for 44% and 46% of bacterial meningitis, respectively, and 23% of pneumococci were intermediately resistant to penicillin. Inability to feed, bulging fontanelle, convulsions in young children, neck stiffness, fever and "staring eyes" were all independently associated with bacterial meningitis. Conjugate Hib vaccine must be given to infants as early as possible. Conjugate pneumococcal vaccines, maternal immunization with 23-valent vaccine and pneumococcal protein vaccines are under investigation for prevention of pneumococcal disease.     

肺炎链球菌抗原/抗体检测及其在肺炎/脑膜炎病原学诊断中的应用

肺炎是小儿的常见疾病,是导致儿童死亡的主要原因。细菌性脑膜炎是儿童重症感染性疾病,具有发病率高、病死率高、后遗症发生率高等特点。肺炎链球菌(SP)是引起儿童社区获得性肺炎、中耳炎、脓毒症、细菌性脑膜炎等细菌感染性疾病的主要病原菌。明确SP病原是临床合理应用抗生素的前提。细菌分离培养法仍是目前明确SP感染的"金标准",但培养阳性率低,耗时较长,不利于SP快速检测。免疫层析试验、酶联免疫吸附试验、胶乳颗粒凝集试验等免疫学方法具有快速、特异性强、灵敏性较高、操作简便、不受抗菌药物影响等优点,是检测SP感染细菌培养之外的一种补充。     

Direct detection of the multidrug resistance genome of Haemophilus influenzae in cerebrospinal fluid of children: implications for treatment of meningitis

BACKGROUND: Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the causative agent by culture and increases reliance on antigen detection. OBJECTIVE: We aimed to develop a PCR assay for detecting the family of Haemophilus integrating and conjugative elements (ICEs) represented by ICEHin1056 among antibiotic resistant Hib, and then apply this directly to CSF to diagnose Hib meningitis and predict organism susceptibility, irrespective of culture results. STUDY DESIGN: Primers specific for orf 51 of ICEHin1056 were designed and multiplexed with Bex primers, specific for H. influenzae, and tested on culture positive and negative cases. RESULTS: Of 73 Hib isolates, orf 51 PCR amplicons, predicting the presence of ICEs, were found in all 33 MDR isolates while only in 1 of 33 sensitive strains. The remaining 7 ampicillin susceptible, chloramphenicol and tetracycline resistant strains did not produce a PCR product to orf 51. PCR amplification from CSF specimens of these culture positive cases produced identical results with 100% and 97% positive and negative predictive values, respectively. Multiplex PCR to detect Bex and orf 51 identified another 16 MDR Hib cases among 81 culture-negative CSF samples. CONCLUSIONS: Direct PCR for orf 51 in CSF identified resistance pattern of 51% more Hib strains than culture alone (110 versus 73). The ability to detect MDR, in culture negative Hib meningitis cases has significant implications for better directing antibiotic treatment of meningitis cases and thus for preventing disability and death.     

儿童肺炎链球菌脑膜炎的临床特点及耐药性分析

目的分析儿科住院患儿肺炎链球菌(SP)脑膜炎的临床特征,同时对培养出的SP菌株进行抗菌药物耐药性分析,以帮助临床早期诊断,合理选用抗菌药物。方法回顾性分析2008年9月至2014年3月收治的14例SP脑膜炎患儿的临床资料并进行耐药性分析。结果 14例SP脑膜炎患儿中,高热13例(93%),抽搐9例(64%),合并败血症7例(50%)。白细胞计数增高11例(79%),CRP增高10例(71%)。所有患儿脑脊液有核细胞计数增高,分类均以中性粒细胞为主,9例(64%)患儿脑脊液蛋白定量结果 1 000 mg/d L。经治疗后10例(71%)患儿痊愈,2例(14%)患儿有后遗症,2例(14%)患儿死亡。SP对青霉素、红霉素、克林霉素、四环素和磺胺耐药率高,均高于60%,对阿莫西林耐药率较低(7%),未发现对万古霉素、氯霉素、左旋氧氟沙星耐药菌株。结论实验室辅助检查指标对于区分SP脑膜炎和其他病原菌引起的脑膜炎无特异性。SP对儿科临床常用抗菌药物耐药情况严重,因此对SP的耐药情况应进行检测,以指导临床用药。