Haemophilus influenzae Infections among Hospitalized Adult Patients

Summary Background: Relatively few data are available about Haemophilus influenza (Hi) infection among adults. Materials and Methods: We studied all adult patients with Hi infection hospitalized between 1988 and 1997 at the University Hospital of Berne. Data were abstracted retrospectively from clinical charts and microbiology records using a standardized questionnaire. Results: 12 invasive and 19 noninvasive Hi infections were observed during the study period. The main clinical manifestations were pneumonia (38.7%), bronchitis (29.0%) and meningitis (12.9%). Most patients (71.8%) had underlying condition. Lethality was high (22.6%), especially in pneumonia patients (50%). The frequency of meningitis caused by Hi serotype b (Hib) seemed to decrease after 1990 when conjugated vaccines against Hib were introduced. Conclusion: Hi remains an important cause of lower respiratory and invasive disease associated with high lethality among polymorbid adult patients. The frequency of Hib infections may also decrease in adults due to herd immunity induced by universal vaccination of children. Received: May 14, 2000 · Revision accepted: October 10, 2000     

The frequency of non-typeable Haemophilus influenzae systemic disease in children

95 strains of Haemophilus influenzae (H. influenzae) isolated from blood of the patients with systemic infections were serotyped by staphylococcal coagglutination during the ten years from 1992 through 2001. As a result, 92 (96.8%) cases were caused by type b strains and 3 (3.2%) cases were caused by non-typeable strains. Three cases with systemic infection due to non-typeable H. influenzae were reported. One patient was a premature neonate with sepsis and respiratory failure who had a fulminant course and died. The other two patients were a 3-year-old girl and a 1-month-old boy both with pneumonia. About their underlying conditions, one received intravenous steroid therapy and the other suffered from respiratory syncytial virus infection. They were treated with appropriate antibiotics and their clinical courses were satisfactory and uncomplicated. Non-typeable H. influenzae was isolated from not only blood but also the lower respiratory tract in all three cases. Systemic infection due to non-typeable strain is rare. But, it should be recognized as a substantial proportion of the serious infections caused by H. influenzae.     

Nontypable Haemophilus influenzae nosocomial pulmonary infections in children following intubation

Twenty-nine intubated pediatric patients were prospectively studied to determine whether nontypable Haemophilus influenzae (NTHI) is associated with the development of nosocomial pneumonia. Throat cultures and tracheal Gram stains, leukocyte counts and cultures were obtained immediately following intubation, then serial studies on tracheal secretions were performed. Median patient age was 13 months. One patient had preexisting lung disease and 14 (48%) had pneumonia when intubated. There were five deaths. NTHI was recovered from the initial throat or tracheal culture in seven patients (24%); none developed a nosocomial lower respiratory tract infection. NTHI was not associated with any of three cases of nosocomial pneumonia. Three of 12 NTHI isolates were beta-lactamase producers. Tracheal leukocyte counts and Gram stains were not predictive of pneumonia, either at the time of intubation or subsequently. We conclude that NTHI in the oropharynx or trachea is not predictive of pneumonia among intubated pediatric patients.     

Studies of treatment for Haemophilus influenzae type b meningitis in children

We summarize 41 cases of bacterial meningitis in the last 11 years caused by Haemophilus influenzae. All isolates were serotype b strain (Hib). Initial chemotherapy was started with ceftriaxone (CTRX) in 22 cases, ampicillin plus cefotaxime (CTX) in 9, CTRX plus panipenem/betamipron in 5, and CTX in 2. Some 31 cases were treated mainly with CTRX. Although therapeutic antibiotics showed good susceptibility for isolates, 8 complicated cases (19.5%) occurred. Sequalae were observed in 7 (17.1%) but none were fatal. Five strains with elevated MIC of CTX (0.12 to 1 microg/mL) recovered after 2001, and 3 of 5 strains also showed elevated MIC of CTRX (0.12 to 0.5 microg/mL), but all were cured completely with CTRX. At present, no treatment failures due to antibiotic resistance have been observed, and CTRX remains suitable as initial therapy for Hib meningitis. A decline in susceptibility for third-generation cephalosporin against beta-lactamase-nonproducing ampicillin-resistant H. influenzae is emerging, however, so it will be necessary to consider combination therapy with CTRX given the foreseeable trend in MICs.     

Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection

The incidence of Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection (ARI) under 5 years was carried out by throat swab culture, blood culture, body fluid or tissue culture in 688 patients from a community, 744 patients from a teaching hospital in Bangkok, 766 normal children from the community and 303 children from a hospital well baby clinic. H. influenzae was found in the throats of 15-20% of patients and in the throats of 4-6% of normal children (p less than 0.001 for both hospital and community patients). Only 12/332 strains (3.6%) of H. influenzae were type b. The rest of H. influenzae were non type b. The most common biotype of H. influenzae non type b was biotype II. S. pneumoniae was found in hospital patients in highly significant numbers compared to the controls (12% vs 4%). No significant difference was observed in strains from the community patients.     

Haemophilus influenzae in chronic bronchitis

Colonization of the adult respiratory tract with nontypable Haemophilus influenzae is a dynamic process with new strains being acquired and replacing old strains periodically.The organism is a common cause of exacerbations of chronic bronchitis based on 3 lines of evidence: quantitative culture of the lower airways obtained by protected specimen brush, antibiotic trials, and serological studies. Nontypable H. influenzae expresses multiple adhesin molecules that mediate adherence to the respiratory tract mucosa. Recent studies have established that the bacterium penetrates the mucosal surface and survives intracellularly and in the interstitium of the submucosa. The organism shows a remarkable degree of antigenic diversity on its surface, including phase variation of lipooligosaccharide, antigenic heterogeneity of surface proteins, point mutations in genes encoding surface proteins and horizontal transfer of genes. These strategies facilitate evasion of the human immune response. Substantial progress has been made in identifying vaccine antigens to prevent infections caused by nontypable H. influenzae.     

Epidemiology of rob beta-lactamase among ampicillin-resistant Haemophilus influenzae isolates in the United States

We surveyed 161 clinical isolates of ampicillin-resistant, beta-lactamase-producing isolates of Haemophilus influenzae obtained between 1975 and 1985 to determine whether they produced TEM-1 or Rob beta-lactamase. Plasmid DNA was obtained from a Rob-producing isolate, F990, and a plasmid (pBR322) known to encode TEM-1. Both plasmids were labeled with 32P and hybridized to whole cell DNA obtained from the clinical isolates. All 161 isolates hybridized with one of the plasmid probes and could be classified as TEM-1- or Rob-producing isolates. Analysis of the distinctive pH profiles of the two beta-lactamases was used to confirm the findings of the DNA hybridization assay. Overall, 13 (8%) isolates obtained from patients in California, North Carolina, Tennessee, Missouri, Louisiana, and Mississippi produced the Rob beta-lactamase. The remaining isolates elaborated the TEM-1 enzyme. We conclude that ampicillin resistance in H. influenzae may be mediated by the production of Rob beta-lactamase and that the occurrence of this enzyme is not limited to the two isolates described to date.     

Epidemiology of colonization by nontypable Haemophilus influenzae in children: a longitudinal study

Eighty-six nasopharyngeal isolates of Haemophilus influenzae were prospectively obtained from three children who attended a day care center from infancy until early childhood (five to seven years). A majority of the strains were nontypable. We analyzed strains by comparing their biotypes and by performing electrophoresis of outer membrane proteins on polyacrylamide gels. Profiles of outer membrane proteins were very heterogeneous and could not be used as the basis for the development of a subtyping scheme. The children characteristically carried a nasopharyngeal strain defined by a unique outer membrane pattern for a period of months, lost it, and then acquired a new strain. We probed the outer membrane proteins of a child's strains by the western blot technique with serum obtained serially from the child. Isolates whose outer membrane proteins appeared identical on stained gels generally had similar antigenic bands on western blots but were occasionally immunologically distinct. Serum immunoglobulins of the IgG class that reacted with the outer membrane proteins did not appear to change greatly over time or to play a role in preventing or terminating colonization. We conclude that nasopharyngeal colonization in children by nontypable H. influenzae is a dynamic process and that factors that cause loss and acquisition of strains remain to be determined.     

Invasive Haemophilus influenzae disease in adults

In a five-year period, 29 cases of bacteremia and/or meningitis in adults caused by Haemophilus influenzae were seen in our large community hospital. There were 17 cases of bacteremic pneumonia and 12 cases of serious extrapulmonary infections. The extrapulmonary infections included cases of endocarditis, meningitis, cholecystitis, epiglottitis, tubo-ovarian abscess, and cellulitis. In contrast with the pediatric experience, H influenzae type B was the causative pathogen in only 45% of patients and only one isolate was ampicillin resistant.     

Antimicrobial resistance in Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharynx in children

The aims of this study are to investigate the antimicrobial susceptibility of bacteria isolated from children and clarify the risk factors for the carriage of the resistant strains. We examined the minimum inhibitory concentrations (MICs) of antimicrobial agents against 949 strains of Streptococcus pneumoniae (S. pneumoniae) and 791 strains of Haemophilus influenzae (H. influenzae) isolated at our department between September, 2001 and May, 2003. Of those, 226 S. pneumoniae strains and 115 H. influenzae strains were analysed for the resistance genes. Also we retrospectively reviewed the profiles of 1,359 patients with either S. pneumoniae, H. influenzae, or both in nasopharynx. From the view point of MICs, PSSP strains were 185 (19%), PISP strains were 443 (47%), and PRSP strains were 321 (34%) in 949 S. pneumoniae strains, and BLNAS strains were 545 (69%), low-BLNAR strains were 104 (13%), BLNAR strains were 81 (11%), and BLPAR strains were 61 (8%) in 791 H. influenzae strains. The results of gene analysis showed that all resistant strains by MICs such as PISP, PRSP, BLNAR, and BLPAR had resistant genes and that 55% of and 21% of susceptible strains of S. pneumoniae (PSSP) and H. influenzae (BLNAS), respectively, had resistant genes. From the investigation for profiles of 1,359 patients, age less than 3 years old, day nursery, and use of antimicrobial agents in last 3 month, seemed to be the risk factors for carriage of resistant strains. To prevent the resistant bacteria from disseminating we should re-consider how to use the antimicobial agents and nurse the young children.     

Spectrum of disease due to Haemophilus influenzae type b occurring in vaccinated children

Haemophilus b polysaccharide vaccine was first licensed in the United States in April 1985. Between May 1985 and September 1987, 228 reports of disease due to Haemophilus influenzae in vaccinated children were submitted to the Food and Drug Administration, of which 216 were accepted for analysis. We compared the relative frequencies of the different disease entities caused by H. influenzae type b reported in vaccinated children with those reported in unvaccinated children (greater than 1000 cases that occurred between 1973 and 1984, as reported in the literature). Over 90% of the vaccinated children were greater than or equal to 24 mo of age. A higher proportion of cases was reported to have occurred within the first two months after vaccination, with 10 cases occurring within 72 h of vaccination. Vaccination did not alter the expected frequencies of the different clinical entities associated with invasive H. influenzae disease. No estimates of clinical efficacy are possible based on the adverse events submitted to the Food and Drug Administration.     

Resistance to trimethoprim in Haemophilus influenzae

Summary The mechanisms of resistance to trimethoprim in eleven U.K. clinical isolates ofHaemophilus influenzae were studied. The levels of dihydrofolate reductase (DHFR) activities in crude extracts from four resistant wild-types were similar to those in susceptible controls. However, activities in extracts from the other seven resistant wild-type isolates, and transformants of two of these, were at least triple those in the sensititive strains. Resistance to trimethoprim was also selected forin vitro during prolonged exposure to the drug and was associated with increased levels of DHFR specific activity in the mutants. DHFR enzymes were, however, still very susceptible to inhibition by trimethoprim. Activities in four extracts, including one from a transformant of a resistant mutant, were reduced by at least 45% following incubation with 10^–8 M trimethoprim. The results suggested that overproduction of the chromosomal DHFR enzyme may be the resistance mechanism in some organisms. The much lower DHFR activities measured in extracts from other resistant isolates may reflect synthesis of chromosomal enzymes that have reduced susceptibility to trimethoprim.

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Trimethoprim-Resistenz bei Haemophilus influenzae

Zusammenfassung Resistenzmechanismen gegen Trimethoprim wurden bei 11 britischen Isolaten vonHaemophilus influenzae untersucht. Die Dihydrofolat-Reduktase-Aktivitäten in ungereinigten Extrakten aus vier resistenten Wildtyp-Stämmen waren mit denen empfindlicher Kontrollen vergleichbar. Dagegen waren die Enzymaktivitäten in den Extrakten aus den anderen sieben Wildtyp-Isolaten und aus Transformanten zwei dieser Stämme mindestens dreimal so hoch wie bei empfindlichen Stämmen. Gegen Trimethoprim resistente Stämme wurdenin vitro bei längerer Exposition gegenüber der Substanz selektiert. Die Resistenz der Mutanten war mit erhöhter Dihydrofolat-Reduktase-Aktivität assoziiert. Dennoch waren die Dihydrofolat-Reduktasen jeweils sehr gut durch Trimethoprim hemmbar. Nach Inkubation mit 10^–8M Trimethoprim wurden die Enzymaktivitäten in den vier Extrakten einschließlich dem Extrakt aus dem Transformanten einer resistenten Mutante um mindestens 45% reduziert. Nach diesen Ergebnissen ist möglicherweise die Überproduktion des chromosomal kodierten Enzyms Dihydrofolat-Reduktase bei einigen Stämmen für die Resistenz verantwortlich. Die sehr viel niedrigeren Dihydrofolat-Reduktase-Aktivitäten in Extrakten anderer resistenter Isolate könnten darauf beruhen, daß in diesen Stämmen chromosomal kodierte Enzyme mit verminderter Empfindlichkeit gegenüber Trimethoprim gebildet werden.

     

Parenteral aztreonam in the treatment of Haemophilus influenzae type b meningitis in Egyptian children

13 children, 8 girls and 5 boys, aged 2-15 months (mean 8.5 months), with Haemophilus influenzae meningitis were treated with aztreonam. Aztreonam was administered intramuscularly in a dose of 50 mg/kg every 8 h. 10 of the infants were in coma and 3 were drowsy when first examined in hospital. All except 2 infants, who were in coma and who died within 24 h of starting therapy, recovered quickly. All patients became fully alert within 4-5 days and afebrile within 5 to 6 days.     

临床分离流感嗜血杆菌和副流感嗜血杆菌的耐药性研究

目的 了解上海部分医院分离的流感和副流感嗜血杆菌对常用抗菌药物的敏感性、对β内酰胺类和喹诺酮类药物的耐药机制以及耐药菌株的克隆传播情况.方法 以琼脂稀释法测定氨苄西林等13种抗菌药物对2006年上海5所医院临床分离的156株嗜血杆菌属细菌的体外抗菌活性,头孢硝噻吩纸片法检测β-内酰胺酶,PCR扩增检测TEM和ROB型β-内酰胺酶基因和喹诺酮类耐药株的喹诺酮耐药决定区,以肠杆菌科基因间重复序列聚合酶链反应(ERIC-PCR)比较细菌的同源性.药物敏感性试验结果采用χ2检验,ERIC-PCR条带模型转换数据进行聚类分析.结果 109株流感嗜血杆菌对氨苄西林敏感率为74.3%,而对氨苄西林舒巴坦、头孢菌素类、氟喹诺酮类等敏感率为100.0%.109株流感嗜血杆菌和47株副流感嗜血杆菌β-内酰胺酶产酶率分别为25.7%和19.1%(χ2=0.776,P=0.378),产酶株均检测到TEM基因.109株流感嗜血杆菌中仅1株对环丙沙星耐药,其gyrA基因存在84位丝氨酸突变为亮氨酸,parC基因存在206位甘氨酸突变为精氨酸.ERIC-PCR结果显示,106株流感嗜血杆菌在85%相似度水平可被分为73型.结论 上海地区流感嗜血杆菌临床菌株对除氨苄西林外的其他常用抗菌药物仍保持很高的敏感率.受试流感嗜血杆菌对氨苄西林耐药的主要机制均为产TEM型β-内酰胺酶.在包括氨苄西林耐药株在内的流感嗜血杆菌中,克隆传播尚不普遍.