Clonal diversity of Haemophilus influenzae carriage isolated from under the age of 6 years children.

OBJECTIVES: Pharyngeal carriers such as H. influenzae seem to constitute the only reservoir and probably the only transmission vehicle of the invasive disease. The aims of this study were to estimate the prevalence of H. influenzae carriage, to characterize antibiotic susceptibility, and to explore genetic diversity of H. influenzae isolates. Sampling was carried out as nasopharynx swabs among children less than 6 years old volunteers. After traditional biochemical tests, isolates were confirmed by targeting omp6 sequence. Following the susceptibility tests, genomic diversity of strains was analyzed by Pulsed-Field Gel Electrophoresis procedure. RESULTS: Out of 328 nasopharynx swabs, 73 strains were identified as H. influenzae. Among H. influenzae isolates, resistance to chloramphenicol (42%) and ampicillin (43%) was observed. Levofloxacin is the most effective antibiotic and the least effect belonged to tetracycline. By genomic analysis of selected H. influenza, 28 PFGE patterns were achieved among which 11 patterns included at least 2 strains. All strains clustered into 25 different clones. The dendrogram analysis of the isolated H. influenzae strains showed that some of these strains had a clonal relationship and common genetic origin. According to our results, antibiotic resistance didn't show any significant correlation with the clonality of strains.

[Clinical characteristics of 84 children with invasive Haemophilus influenzae infection from 2014 to 2018].

Objective: To investigate the clinical characteristics of invasive Haemophilus influenzae (HI) infection in children. Methods: The clinical manifestations, laboratory examinations and treatment outcomes of 84 children with HI infection confirmed by bacterial culture in 7 tertiary children's hospitals from 2014 to 2018 were analyzed retrospectively. Results: Among the 84 cases, 50 were males. The age was 1.54 years (ranged from 5 days to 13 years).Twenty cases (24%) had underlying diseases and 48 cases (57%) had not received antibiotics before collecting specimens. Eighty-two cases (98%) had fever and 75 cases (89%) had clear infection foci, among which 31 cases (37%) had meningitis and 27 cases (32%) had pneumonia. Blood culture was positive in 62 cases (74%), cerebrospinal fluid culture was positive in 10 cases (12%), blood culture and cerebrospinal fluid culture were both positive in 11 cases (13%). Antibiotics susceptibility test showed that 27% (22/82) of all HI strains produced ß-lactamases and 48% (37/77) strains were resistant to ampicillin. The drug resistance rates to cefuroxime, ampicillin-sulbactam, trimethoprim-sulfamethoxazole and azithromycin were 25% (20/80) , 20% (9/45) , 71% (44/62) and 19%(11/58), respectively. All strains were sensitive to meropenem, levofloxacin and ceftriaxone. After sensitive antibiotic therapy, 83% (70/84) of all patients were cured and improved, the mortality rate and loss of follow-up rate were 13% (11/84) and 4% (3/84) respectively. Conclusions: Meningitis and pneumonia are common presentation of invasive HI infections in children. Mortality in HI meningitis children is high and the third generation of cephalosporins, such as ceftriaxone can be used as the first choice for the treatment of invasive HI infection.

Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical treatment of Haemophilus influenzae-associated lower respiratory tract infections in adults; a retrospective propensity score-matched study.

There is consensus that definitive therapy for infections with H. influenzae should include antimicrobial agents with clinical breakpoints against the bacterium. In Scandinavia, benzylpenicillin is the recommended empirical treatment for community-acquired pneumonia (CAP) except in very severe cases. However, the effect of benzylpenicillin on H. influenzae infections has been debated. The aim of this study was to compare the outcomes of patients given benzylpenicillin with patients given wide-spectrum beta-lactams (WSBL) as empirical treatment of lower respiratory tract H. influenzae infections requiring hospital care. We identified 481 adults hospitalized with lower respiratory tract infection by H. influenzae, bacteremic and non-bacteremic. Overall, 30-day mortality was 9% (42/481). Thirty-day mortality, 30-day readmission rates, and early clinical response rates were compared in patients receiving benzylpenicillin (n = 199) and a WSBL (n = 213) as empirical monotherapy. After adjusting for potential confounders, empirical benzylpenicillin treatment was not associated with higher 30-day mortality neither in a multivariate logistic regression (aOR 2.03 for WSBL compared to benzylpenicillin, 95% CI 0.91-4.50, p = 0.082), nor in a propensity score-matched analysis (aOR 2.14, 95% CI 0.93-4.92, p = 0.075). Readmission rates did not significantly differ between the study groups, but early clinical response rates were significantly higher in the WSBL group (aOR 2.28, 95% CI 1.21-4.31, p = 0.011), albeit still high in both groups (84 vs 81%). In conclusion, despite early clinical response rates being slightly lower for benzylpenicillin compared to WSBL, we found no support for increased mortality or readmission rates in patients empirically treated with benzylpenicillin for lower respiratory tract infections by H. influenzae.

Epidemiological Features and Antibiotic Resistance Patterns of Haemophilus influenzae Originating from Respiratory Tract and Vaginal Specimens in Pediatric Patients.

STUDY OBJECTIVE: Haemophilus influenzae (H. influenzae) is a common pathogen of respiratory tract infections in children, however, as a possible cause of vulvovaginitis in prepubertal girls, its epidemiological features, antibiotic-resistance patterns, and treatment are seldom noted. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Specimens obtained from patients were inoculated on Haemophilus selective medium; and drug-sensitivities tests were determined using the disk diffusion method. A cefinase disk was used to detect ß-lactamase. RESULTS: A total of 610 H. influenzae strains, 81.6% (498/610) from the respiratory tract and 18.0% (110/610) from the vagina, were identified in the Children's Hospital in 2015. The age of the children with respiratory tract strains were significantly younger than those with vaginal strains (P < .001). The H. influenzae isolation rate in May was the highest. The ß-lactamase positive rate was 51.5% (314/610), and 52.5% (320/610) were resistant to ampicillin. The susceptibilities rates to cefuroxime, ampicillin/sulbactam, cefotaxime, clarithromycin, and sulfamethoxazole-trimethoprim were 72.1% (440/610), 95.9%, 96.4% (588/610), 81.8% (499/610), and 36.4% (222/610), respectively. Higher resistance to ampicillin, cefuroxime, clarithromycin, and sulfamethoxazole-trimethoprim were found in respiratory tract strains, compared with vaginal strains (P < .05). All of the patients with H. influenzae in the respiratory tract were cured with oral or intravenous ß-lactam antibiotics. Of all patients with vaginal strains, 50% (55/110) were cured with topical ofloxacin gel, and 44.5% (49/110) were cured with oral ß-lactam antibiotics. CONCLUSION: The drug-resistance rates of H. influenzae isolated from vagina were lower than those from the respiratory tract. Topical ofloxacin gel or oral ß-lactam antibiotics are effective treatments to eliminate the H. influenza causing infection in the vagina.

Haemophilus parainfluenzae as a marker of the upper respiratory tract microbiota changes under the influence of preoperative prophylaxis with or without postoperative treatment in patients with lung cancer.

BACKGROUND: Haemophili are representative microbiota of the upper respiratory tract. The aim of this study was to assess the effects of perioperative antimicrobial prophylaxis and/or postoperative treatment on Haemophilus parainfluenzae prevalence, and antimicrobial sensitivity in short-term hospitalized patients with lung cancer who underwent surgery. RESULTS: Samples were collected from 30 short-term hospitalized patients with lung cancer and from 65 healthy people. The nasal and throat specimens were taken twice from each patient: before (EI, Examination I), on the fourth/fifth day (EII, Examination II) after surgery, and once from healthy people. The isolates identification and antimicrobial susceptibility were detected by routine diagnostic methods. H. parainfluenzae was found in throat specimens of 42/65 (64.6 %) healthy people, while in 19/30 (63.3 %) lung cancer patients in EI (p = 0.6203) and in 13/30 (43.3 %) ones in EII (p = 0.0106). Neither the disease itself nor short-term hospitalization with perioperative prophylaxis alone affected H. parainfluenzae prevalence in EII, while perioperative prophylaxis with postoperative treatment significantly decreased its colonization in EII. The differences in the number of patients colonized by Candida spp. in EI and in EII were observed (p = 0.0082).Totally, 23/58 (39.7 %) of H. parainfluenzae isolates were resistant mainly to beta-lactams; among 11 ampicillin-resistant isolates only 3 were beta-lactamase positive. CONCLUSIONS: The antimicrobial perioperative prophylaxis together with postoperative treatment may disturb the composition of the airways microbiota represented by H. parainfluenzae, in addition to selecting the resistant strains of bacteria and promoting yeasts colonization in lung cancer patients undergoing surgery.

Evaluation of Haemophilus influenzae type b carrier status among children 10 years after the introduction of Hib vaccine in Brazil.

The aim of the present study was to assess the prevalence of Haemophilus influenzae type b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Evaluation of Haemophilus influenzae type b carrier status among children 10 years after the introduction of Hib vaccine in Brazil

The aim of the present study was to assess the prevalence of Haemophilus influenzaetype b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Invasive Haemophilus influenzae Disease, Europe, 1996-2006.

An international collaboration was established in 1996 to monitor the impact of routine Haemophilus influenzae type b (Hib) vaccination on invasive H. influenzae disease; 14 countries routinely serotype all clinical isolates. Of the 10,081 invasive H. influenzae infections reported during 1996-2006, 4,466 (44%, incidence 0.28 infections/100,000 population) were due to noncapsulated H. influenzae (ncHi); 2,836 (28%, 0.15/100,000), to Hib; and 690 (7%, 0.036/100,000), to non-b encapsulated H. influenzae. Invasive ncHi infections occurred in older persons more often than Hib (median age 58 years vs. 5 years, p<0.0001) and were associated with higher case-fatality ratios (12% vs. 4%, p<0.0001), particularly in infants (17% vs. 3%, p<0.0001). Among non-b encapsulated H. influenzae, types f (72%) and e (21%) were responsible for almost all cases; the overall case-fatality rate was 9%. Thus, the incidence of invasive non-type b H. influenzae is now higher than that of Hib and is associated with higher case fatality.

Haemophilus influenzae Type B conjugate vaccine introduction in Mali: impact on disease burden and serologic correlate of protection.

In Bamako, Mali, where surveillance revealed a high incidence of Haemophilus influenzae type b (Hib) invasive disease, Hib conjugate vaccine was introduced into the Expanded Program on Immunization and the impact assessed. Annual confirmed Hib hospitalizations for infants 0-11 months of age fell from 175/10(5) to 44/10(5) (P < 0.001); among infants 6-7 months of age Hib hospitalizations fell from 377/10(5) to 69/10(5), (82% decrease, P < 0.001). Invasive Streptococcus pneumoniae hospitalizations remained unchanged. In a baseline serosurvey, only 3/200 infants 6-7 months of age (1.5%) had protective anti-polyribosylribitol phosphate (PRP) titers > or = 0.15 microg/mL and 1(0.5%) had >or = 1.0 microg/mL. In serosurveys 18 and 30 months after vaccine introduction, 168/201 (84%) and 184/200 (92%) infants, respectively, had titers > or = 0.15 microg/mL and 141/201 (70%) and 163/200 (82%) had titers > or = 1.0 microg/mL. Introduction of Hib vaccine led to rises in anti-PRP seroprevalence, significant reductions in Hib disease, and all-cause hospitalizations, whereas S. pneumoniae disease remained unchanged.

Haemophilus influenzae type-b and non-b-type invasive diseases in urban children (<5years) of Bangladesh: implications for therapy and vaccination.

OBJECTIVE: To prospectively study the epidemiology and antibiotic resistance of Haemophilus infuenzae isolates from invasive infections in children. METHODS: Children (<5years) with pneumonia, meningitis and septicemia from three hospitals in Dhaka, Bangladesh were enrolled (1999-2003); clinical and laboratory data, and blood for cultures were collected. Cerebrospinal fluid (CSF) of meningitis cases was analyzed (Gram stain, culture and biochemical tests). Hib antigen was detected by latex agglutination (LA) in culture-negative pyogenic CSF and PCR was done for bexA gene in culture- and LA-negative pyogenic CSF. Antibiotic susceptibility was determined by E-Tests and beta-lactamase by nitrocefin stick. RESULTS: Seventy-three cases of H. influenzae infections (46 of 293 meningitis cases, 25 of 1493 pneumonia cases, 2 of 48 septicemia cases) were detected; 63%, 34% and 3% of them had meningitis, pneumonia and septicemia respectively. H. influenzae type b (Hib) caused infections in 80.8% of cases (60.3% meningitis, 20.5% pneumonia). Most (86%) infections clustered in 4-12month infants. The case-fatality in pneumonia was 8% compared to 19% in meningitis. H. influenzae isolates from pneumonia and meningitis children were equally resistant to antibiotics (46% vs 43%). Of 10 drugs tested, isolates were resistant to ampicillin (31%), chloramphenicol (42%), trimethoprim-sulfamethoxazole (44%) and azithromycin (1.4%). Multidrug-resistant (MDR) strains were equally prevalent in Hib (31%) and non-b-type (29%) isolates, and in pneumonia (31%) and meningitis (34%) cases. None was resistant to amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin. Of all H. influenzae infections, 40%, 4.4% and 100% of pneumonia, meningitis and septicemia cases were caused by other serotypes or non-typeable strains. All ampicillin-resistant-strains produced beta-lactamase without detection of beta-lactamase-negative-ampicillin-resistant (BLNAR) strains. CONCLUSION: Hib is a leading cause of invasive bacterial infections in infants. Multidrug-resistant H. influenzae is common and requires amoxicillin-clavulanate, ceftriaxone or azithromycin as empirical therapy with specific recommendation for use of ceftriaxone for treatment of meningitis particularly MDR cases. New fluoroquinolines has potential utility. An effective national Hib vaccination programme is essential in Bangladesh although non-Hib infections will remain an issue.

Impact of antimicrobial resistance on health outcomes in the out-patient treatment of adult community-acquired pneumonia: a probability model.

Out-patient treatment of community-acquired pneumonia (CAP) is a major challenge in an era of increasing prevalence of antimicrobial resistance. However, data describing the clinical impact of such resistance are scarce. A probability model was developed to estimate the impact of antimicrobial resistance on clinical outcomes for adults with CAP, eligible for out-patient care. The model assumed patients would be evaluated at 48-72 h, with those failing to improve being either hospitalized or switched to a different antibiotic. Two strategies were considered: amoxicillin followed by erythromycin (amoxicillin/erythromycin) and erythromycin followed by levofloxacin (erythromycin/levofloxacin). Analyses were conducted based on susceptibility of the major pathogens in France and the UK. Primary model-generated outcome measures were the proportion of patients successfully treated with first-line therapy and the proportion of patients subsequently hospitalized. The model estimated that in France, the amoxicillin/erythromycin strategy would lead to 67.8% improving within 48-72 h and 12.7% subsequently being hospitalized, compared with 48.6% and 13.7% for erythromycin/levofloxacin. For the UK, first-line success and hospitalization rates were, respectively, 71.7% and 8.1% for amoxicillin/erythromycin, and 65.3% and 9.3% for erythromycin/levofloxacin. The model estimated that antimicrobial resistance was responsible for >40% of hospitalizations in France and 15% in the UK. These data suggest that in areas with substantially reduced levels of susceptibility, antimicrobial resistance may be a significant contributor to subsequent hospitalization in adults initially treated as out-patients for CAP. Choice of out-patient treatment strategy should consider local resistance rates in order to maximize the likelihood of early cure, thereby minimizing hospitalizations.

[Haemophilus influenzae sensitivity to beta-lactamines]. / Sensibilité d'Haemophilus influenzae aux bêta-lactamines.

FACTS: Among the 280 strains studied, 106 were sensitive to beta-lactams, 92 were beta-lactamase producers, and 82 non-producers of beta-lactamase had reduced sensitivity to beta-lactams. QUESTION: The results of this study illustrate the complexity of characterizing the phenotypic resistance of H. influenzae and raises the question of which in vitro susceptibility tests best identify resistance.

Respiratory tract infection: epidemiology and surveillance.

Streptococcus pneumoniae and Haemophilus influenzae are the key pathogens implicated in bacterial infections of the upper and lower respiratory tract. Choice of empiric oral antimicrobial chemotherapy is guided by the clinical presentation, severity of the infection and epidemiological knowledge. beta-Lactams and the macrolides are the two major groups of antibiotics used to treat respiratory tract infections. The prevalence of penicillin-resistant strains of S. pneumoniae is increasing world-wide (up to 30% in the USA), as is the prevalence of beta-lactamase-producing strains of H. influenzae. Macrolide resistance in S. pneumoniae is increasing and is absolute, and some of the macrolides have only limited activity against H. influenzae. Knowledge of local and global antibiotic resistance patterns should be used as the key to directing empiric choice of antibiotic treatment.

Serotypes and antimicrobial susceptibility of Haemophilus influenzae.

During a one year prospective study of Haemophilus influenzae infections in patients treated in hospitals in the metropolitan area of Cape Town. H. influenzae type b accounted for 81.7% of 126 invasive isolates, whereas 86.1% of the 280 non-invasive isolates were non-typeable. Ampicillin resistance was detected among 10.8% of strains of which all but one produced beta-lactamase. All strains were susceptible to cefotaxime as were more than 95% to chloramphenicol, rifampicin, tetracycline but 20.4% were resistant to co-trimoxazole and 87.2% to erythromycin.

[Oropharyngeal flora. Epidemiologic survey of prevalence]. / Flores oropharyngées. Enquête épidémiologique de prévalence.

OBJECTIVES: Epidemiological surveys which are not frequently carried out in medical practice should provide useful information for the choice of antibiotics to be prescribed in community-acquired infections particularly with the recent development of therapeutic difficulties due to resistant strains. We therefore analyzed the prevalent pharyngeal flora in a general patient population. METHODS: The study was conducted during a single 24-hour period in 1991 by 43 general practitioners and included 645 subjects consulting for benign affections. No patient selection was made. Two pharyngeal swabs were obtained from each subject and cultured in aerobic and anaerobic conditions. Internationally accepted methods for identifying bacteria in pharyngeal samples all performed by one well-equipped laboratory. Beta-lactamase activity was determined with the nitrocephine technique, both directly and after culture. RESULTS: Patient age varied from 16 to 45 years; most (68.5%) consulted for reasons other than ear-nose-throat affections. Only 41 patients (4.3%) consulted for sore throat and 65.4% had not received antibiotics for at least 6 months. Haemophilus influenzae was found in 59.6% of the patients, 20% of the strains were beta-lactamase producers as were 83.7% of the Moraxella catarrhalis strains identified. CONCLUSION: These factors are indicators of potential risk of therapeutic failure when using beta-lactams unstable to beta-lactamases for the treatment of pharyngeal infections.

Epidemiology of invasive Haemophilus influenzae infections in Cape Town, South Africa.

The full spectrum of invasive Haemophilus influenzae disease has not been documented previously in Africa. This 1-year prospective study was designed to determine the epidemiology of invasive Haemophilus influenzae disease in Cape Town children. During this period, 142 children with invasive disease were hospitalized; 85 (59.9%) presented with meningitis, 35 (24.6%) with pneumonia and 22 (15.5%) with other diseases. No cases of epiglottitis were seen. Sixty per cent of cases were male and 40% female. The median age of the children was 9 months, with a range of 1-144 months, and 65.5% were aged < 12 months. Neurological dysfunction was noted in 40% and 18% of children with meningitis on admission and discharge, respectively. The overall case fatality rate (95% confidence intervals) was 9.2% (4.9-15.7), and for meningitis, pneumonia and septicaemia it was 4.7% (1.2-16.4), 14.3% (4.6-31.8) and 40% (8-78.1), respectively. Serotype b accounted for 86.5% of all cases, 97.3% of cases of meningitis, 71.4% of cases of pneumonia, 50% of cases of septicaemia, all cases of arthritis and cellulitis and none of mastoiditis. The incidence rates (95% confidence intervals) for all invasive type b infections were 169 (122-198) and 47 (39-57) per 100,000 population for children < 1 and < 5 years, respectively. For meningitis the rates were 112 (84-148) and 34 (25-40) per 100,000, respectively. Rates for mixed race and white children were similar, but those for black children were more than double those rates.(ABSTRACT TRUNCATED AT 250 WORDS)

[Invasive Haemophilus influenzae type B infections in infancy (1981-1990)]. / Infecciones invasivas por Haemophilus influenzae tipo B en la infancia (1981-1990).

We report the epidemiology of invasive Haemophilus influenzae type B infections. The study is based on 58 children and was carried out during the years from 1981 to 1990. Sixty-three percent of the patients had meningitis, 10.3% had arthritis, 10.3% had epiglottitis, 8.6% had cellulitis and 6.9% had pneumonia. Thirteen percent of the cases were children who were less than 6 months old, 34.4% were less than 12 months old, 70.6% were less than 24 months of age and 93% were less than 4 years old. Among the latter, 90% of the children with epiglottis or pneumonia were 24 months or older compared with 16% of the patients with meningitis, arthritis or cellulitis (p < 0.001). Sixty-three percent of the isolated strains of Haemophilus influenzae type B were resistant to ampicillin and 19.2% of the strains were resistant to ampicillin and chloramphenicol.

In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains of Haemophilus influenzae.

The in vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains of Haemophilus influenzae. Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2-4-fold more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs. The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated. The combination was additive in 92% and synergistic in 8% of all strains of H. influenzae tested; no antagonism was found. The results were independent of the site of isolation of the strain or presence of beta-lactamase. These findings suggest the potential clinical utility of clarithromycin for the treatment of H. influenzae infections.