Effects of repeated infections with non-typeable Haemophilus influenzae on lung in vitamin D deficient and smoking mice.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain. METHODS: Vitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, tissue remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3. RESULTS: VDD enhanced NTHi eradication, independently of CS and complete eradication was reflected by decreased anti-NTHi Ig's within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig's. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig's, anti-dsDNA Ig's and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in patients who were Vitamin D insufficient before treatment. CONCLUSION: During repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS whilst it also promoted autoantibodies. In COPD patients, vitamin D supplementation could be protective against NTHi infections in vitamin D insufficient patients. Future research is needed to decipher the determinants of dual effects of VDD on adaptive immunity. TRAIL REGISTRATION: ClinicalTrials, NCT00666367. Registered 23 April 2008, https://www.clinicaltrials.gov/ct2/show/study/NCT00666367 .

Premature Infant with Haemophilus parainfluenzae Sepsis: Case Report and Literature Review.

Haemophilus parainfluenzae is an unusual causative organism of invasive bacterial infection in adults and children. Mortality and morbidity secondary to Haemophilus parainfluenzae have been documented in the literature. We present a rare case of a premature infant with early onset sepsis caused by Haemophilus parainfluenzae, who was born to a primigravida with chorioamnionitis. The infant was successfully treated for 10 days with antibiotics with no complications.

Antibiotic resistance of Streptococcus pneumoniae in children with acute otitis media treatment failure.

OBJECTIVES: The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in children with acute otitis media (AOM). This study aimed to analyze the types of bacterial strains in fluid isolated from the middle ear of children with AOM who did not respond to oral antibiotic treatment. We also determined the antibiotic resistance of the most frequently isolated bacterial strain (Streptococcus pneumoniae) found in these children. METHODS: This was a prospective study of 157 children with AOM aged from 6 months to 7 years admitted due to unsuccessful oral antibiotic treatment. All children underwent a myringotomy, and samples of the middle ear fluid were collected for bacteriological examination. RESULTS: Positive bacterial cultures were obtained in 104 patients (66.2%), with Streptococcus pneumoniae (39.69%), Haemophilus influenzae (16.03%) Staphylococcus aureus (16.03%), Staphylococcus haemolyticus (6.9%) and Streptococcus pyogenes (5.34%) found most frequently. The majority (65.4%) of S. pneumoniae strains were penicillin-intermediate-resistant or penicillin-resistant, and 67.2% strains of S. pneumoniae were multidrug-resistant. CONCLUSIONS: We identified S. pneumoniae as the most frequently isolated pathogen from the middle ear in children with AOM treatment failure and determined that the majority of strains were antibiotic-resistant. We propose that the microbiological identification of bacterial strains and their degree of antibiotic resistance should be performed prior to therapy in order to choose the most appropriate antibiotic therapy for children with AOM treatment failure.

[Antibiotic resistance of S. pneumoniae and H. influenzae strains isolated from patients with community acquired respiratory tract infections. BACTRO multicenter, multidisciplinary study]. / Spectrul de rezistenta la antibiotice a tulpinilor de S. pneumoniae si H. influenzae izolate de la pacienti cu infectii comunitare de tract respirator. Studiul multicentric, multidisciplinar BACTRO.

UNLABELLED: Community respiratory tract infections are common in clinical practice. Antimicrobial treatment should be promptly administered and guided by a probabilistic approach according to the clinical presentation and local patterns of bacterial resistance. Bacterial resistance is widespread, with large geographical variations related to behaviors in antibiotics prescription. S. pneumoniae and H. influenzae are the most frequent pathogens responsible for respiratory tract infections etiology. METHODS: We assessed the antibiotics susceptibility of S. pneumoniae and H. influenzae strains isolated from patients with community respiratory tract infections, prospectively enrolled over a period of 3 consecutive years, by determining the MIC. Analysis was performed using both cutoffs provided by European Committee on Antimicrobial Susceptibility testing (EUCAST) and CLSI. Consequently we evaluated the influence of different factors associated with the development of bacterial resistance. RESULTS: We analyzed 293 S. pneumoniae strains and 265 H. influenzae strains isolated during 1999-2001, mainly from sputum (68.3% and 74.9% respectively of total isolates). We observed a high proportion of S. pneumoniae resistant to penicillin (6.1% resistant and 48.5% with intermediate susceptibility) and to erythromycin (39% resistant strains). H. influenzae strains were resistant to amoxicillin in 26% of cases and the presence of betalactamase was certified in 13% of tested isolates; 18.3% of H. influenzae strains were resistant to amoxicillin through specific mechanisms other than by producing betalactamase. Other antibiotic resistances were assessed. CONCLUSIONS: In Romania clinician must consider the high prevalence of antibiotic resistance, particulary of S. pneumoniae to macrolides and beta-lactams (thus requiring the use of high doses of betalactams) and the high proportion of beta-lactamase producing H. influenzae.

Empirical treatment of influenza-associated pneumonia in primary care: a descriptive study of the antimicrobial susceptibility of lower respiratory tract bacteria (England, Wales and Northern Ireland, January 2007-March 2010).

OBJECTIVES: To determine the susceptibility of lower respiratory tract (LRT) isolates of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to antimicrobial agents recommended by UK guidelines for treatment of pneumonia associated with influenza-like illness. METHODS: Analysis of antimicrobial susceptibility data from sentinel microbiology laboratories in England, Wales and Northern Ireland was carried out. Subjects comprised patients who had an LRT specimen taken in a general practitioner surgery or hospital outpatient setting between January 2007 and March 2010. The main outcome measurements were antimicrobial susceptibility trends of LRT isolates over time, between patient age groups and in different geographical regions. RESULTS: Susceptibility to tetracyclines or co-amoxiclav was high. Of the 70,288 and 45,288 isolates with susceptibility results for tetracyclines or co-amoxiclav, 96% and 92%, respectively, were susceptible. Overall susceptibility to ciprofloxacin, ampicillin/amoxicillin and macrolides was lower than for tetracyclines or co-amoxiclav and varied markedly by organism. There were few clinically relevant variations in susceptibility to doxycycline or co-amoxiclav over time, geographically or between age groups. CONCLUSIONS: The data support the use of doxycycline or co-amoxiclav as appropriate empiric treatment for LRT infection caused by the pathogens investigated, for patients in primary care.

In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube.

A novel murine model of non-typeable Haemophilus influenzae (NTHi) pneumonia was established. A plastic tube was inserted into the trachea 7 days before bacterial inoculation. Numbers of NTHi recovered from the lungs and trachea were determined for 7 days. Histologically, bronchioles and adjacent alveoli in the intubation group were filled with numerous inflammatory cells. The efficacy of sitafloxacin was compared with ciprofloxacin using the new murine pneumonia model. The data suggest that sitafloxacin displays equivalent efficacy to ciprofloxacin against H. influenzae pneumonia. This new murine NTHi pneumonia model appears useful not only for in vivo evaluation of antibiotics but also for analysis of the pathogenesis of H. influenzae pneumonia.

Antimicrobial susceptibility of cerebrospinal isolates from patients with meningitis.

Str. pneumoniae isolates were susceptible to penicillin, all to also ofloxacin and chloramphenicol and cefotaxim and 39 (100%) to cotrimoxazol. Concerning S. aureus, all isolates 22 were susceptible to oxacillin and chloramphenicol, and 21 also to cotrimoxazol. All N. meningitidis isolates but one-10 of all were susceptible to penicillin, all to cefotaxim, chloramphenicol and cotrimoxazol. All H.influenzae isolates were susceptible to ampicillin and chloramphenicol, as well as to ofloxacin and cotrimoxazol. Those surprisingly high susceptibilities to rather "old" antibiotics may be explained by low antibiotic consumption, accessibility and therefore low usage which is a key promoter of resistance both in community and hospital.

Infecciones invasoras por Haemophilus influenzae tipo b después de la incorporación de la vacuna conjugada al Programa Ampliado de Inmunizaciones en Chile / Invasive infections caused by Haemophilus influenzae type b after the institution of the conjugated vaccine on the Expanded Programm on Immunization in Chile

Tras nueve años desde la introducción en Chile de la vacuna conjugada contra Haemophilus influenzae tipo b (Hib) a las edades de 2-4 y 6 meses, las infecciones por este agente han disminuido notoriamente, pero aún son causa de morbilidad de importancia en algunos pacientes. Se reportan los niños con enfermedad invasora por Hib ocurridas entre los años 2000 y 2004. Para esto se analizaron los egresos del Hospital Padre Hurtado, consignándose epidemiología, clínica, laboratorio, terapia y complicaciones para cada paciente. Durante este período, 23 pacientes (17 varones), con una mediana de edad de 30 meses (rango 1-71 meses) presentaron enfermedad invasora por Hib. Estas se presentaron como neumonía (7), meningitis (4), pleuroneumonía (2), empiema pleural (2), sepsis (2), celulitis (2), meningitis y pleuroneumonía (1), purpura fulminans (1), miositis (1) y epiglotitis (1). No se registraron fallecimientos, pero 4 pacientes presentaron secuelas graves al momento del alta. Veinte pacientes fueron catalogados como falla de vacuna. Hamophilus influenzae b es aún un agente causal de enfermedad grave y con morbilidad asociada en nuestro país, por lo que es importante tener un alto índice de sospecha. Su estudio y notificación son relevantes para la evaluación del esquema de vacunación anti-Hib actualmente utilizado.

N-acetyl-D-glucosamine medium improves recovery of Haemophilus influenzae from sputa of patients with cystic fibrosis.

A modified selective medium supplemented with N-acetyl-D-glucosamine (NAG), hemin, and NAD plus two cefsulodin disks, for primary isolation of nonencapsulated Haemophilus influenzae from sputum of patients with cystic fibrosis, is described. Isolation of H. influenzae from this medium, designated NAG medium, was compared with recovery by standard media and immunochemical detection of H. influenzae with monoclonal antibody 8BD9. The H. influenzae recovery rate increased from 31% with standard media to 42% with NAG medium. H. influenzae was detected by immunoperoxidase staining in 54% of the sputum specimens. The results of this study demonstrate that NAG medium improves H. influenzae recovery, although immunoperoxidase staining is superior for detection of H. influenzae from sputum of cystic fibrosis patients.

Haemophilus influenzae type b purpura fulminans treated with hyperbaric oxygen.

We report the case of a 4-month-old child with purpura fulminans caused by Haemophilus influenzae type b. In addition to conventional therapy, she was treated with hyperbaric oxygen, and made a full recovery. Hyperbaric oxygen as an adjunct to other therapy in purpura fulminans is discussed.

The efficacy of mezlocillin-amikacin combination in febrile neutropenic children with oncologic disease.

The efficacy of mexlocillin-amikacin combination as empirical therapy for febrile neutropenic patients was studied in 30 children (21 males, 9 females) with various oncologic diseases aged 1-15 years (mean age 7.3 +/- 4.4) in the Istanbul Medical School, Oncologic Disease Research and Treatment Center, and Department of Pediatric Hematology-Oncology between January 1 and May 31, 1988. The response rate was 76.6%. Profound persistent granulocytopenia (fewer than 100 ml) was present in 70% of the patients. In 63.3% of patients, the infections were microbiologically documented (60%) Gram(+) and 40% Gram(-). The combination was well tolerated with hepatic and/or renal disturbances in 8 cases (26.6%). We conclude that mezlocillin-amikacin is an effective empirical combination in the initial treatment of infections in febrile neutropenic children with various oncologic diseases.

Randomized study of two dosage regimens of ciprofloxacin for treating chronic bronchopulmonary infection in patients with cystic fibrosis.

Twenty-nine adult patients with cystic fibrosis who had chronic bronchopulmonary infection were randomly assigned to receive 750 or 1,000 mg of oral ciprofloxacin every 12 hours for two weeks. Assessments for efficacy and safety were made on treatment Days 7 and 14 and one week following completion of therapy, and pharmacokinetic data were collected on Days 1, 7, and 14. Fifteen of 28 evaluable patients showed clinical improvement, and none had clinical deterioration. The higher dosage of ciprofloxacin did not enhance the clinical response. Statistically significant, stepwise changes in clinical scores, pulmonary function, and sputum concentrations of Pseudomonas aeruginosa and Staphylococcus aureus were noted, but regression toward initial values occurred by one week after treatment. Although all P. aeruginosa isolates were initially inhibited by 2 mg/liter of ciprofloxacin or less, 45 and 35 percent of isolates were resistant after 14 days of therapy and one week later, respectively. Outpatient oral ciprofloxacin therapy was commonly associated with clinical improvement in adult patients with cystic fibrosis who have chronic bronchopulmonary infection, regardless of the emergence of resistant P. aeruginosa, and adverse reactions were infrequent. Further studies must delineate the long-term consequences of the frequent emergence of bacterial resistance.

Comparison of two different metronidazole regimens in the treatment of Gardnerella vaginalis infection with or without trichomoniasis.

Gardnerella vaginalis infection confirmed by culture was treated either by a 2 g dose or divided doses of metronidazole in 100 and 200 female patients respectively. Both dosages were equally effective. We recommend a single dose of 2 g metronidazole in the treatment of Gard. vaginalis infection, particularly when association with trichomoniasis is confirmed or suspected.

Patterns of illness in the highly febrile young child: epidemiologic, clinical, and laboratory correlates.

Three hundred one episodes of fever greater than or equal to 103 F were documented in 375 infants and young children observed in a comprehensive care clinic during the period October 1974 to October 1978. Of such highly febrile illnesses 79% were accompanied by respiratory tract signs or symptoms, 7% by disease at a site other than the respiratory tract, and 22% of illnesses had no localizing signs or symptoms. Viral cultures were obtained from the respiratory tract in 178 cases and were positive in 68: 57/134 from respiratory illness; 2/4 from illness at sites other than the respiratory tract; and 9/40 in children without localizing disease. Bacterial cultures of the upper respiratory tract were obtained in 191 illnesses, but the overall rate of isolation of Haemophilus influenzae, Streptococcus pneumoniae and group A streptococci (46%) did not differ from that in a group of well children (39%). Bacterial cultures of the blood were obtained in 89 patients with fever greater than or equal to 103 F and in an additional 41 children with lower temperatures. Nine children had documented systemic bacterial disease (eight positive blood cultures and one positive CSF). The rate of clinically apparent systemic bacterial disease in these otherwise normal infants was one bacteremic episode per 94 years of child care.

Hemophilus influenzae purulent pericarditis in children: diagnostic and therapeutic considerations.

Purulent pericarditis is an unusual complication of infection in infancy and has been associated with an extremely high mortality rate. Early diagnosis followed by combined antibiotic therapy and surgical drainage of the pericardium has markedly improved survival. Between APril, 1975, and February, 1979, nine patients with purulent pericarditis secondary to Hemophilus influenzae type B were treated at the Oklahoma Children's Memorial Hospital. In every case signs and symptoms of congestive heart failure were present, and a pericardial effusion was demonstrated by echocardiography and confirmed by pericardiocentesis. The organism was identified with countercurrent immunoelectrophoresis and antibiotic sensitivity determined by rapid beta lactamase assay. All patients were treated with a combination of parenteral antibiotics and open surgical drainage of the pericardium. There were no deaths and all patients demonstrated marked improvement following operation. Follow-up echocardiography revealed no evidence of pericardial effusion or signs of constriction in any patient.