You are here: Home Research Themes Antimicrobial Therapy

Antimicrobial Therapy

Article Reference The isolation and characterization of non-typeable Haemophilus influenzae from the sputum of adult cystic fibrosis patients.
The role of non-typeable Haemophilus influenzae in cystic fibrosis (CF) remains unclear. We wanted, therefore, to determine the presence and characteristics of non-typeable H. influenzae in sputum samples from patients with CF. In order to do this, we have assessed sputum samples from 55 consecutive clinically stable patients seen routinely at an adult CF out-patient clinic. Quantitative bacterial culture was performed using a selective media containing cefsoludin, and isolates were characterized by biotyping and outer membrane protein profile analysis. In 17 (30%) of these samples, non-typeable H. influenzae was isolated and was present in similar viable numbers (mean 7.7 x 10(8) colony-forming units (cfu).mL-1; SEM 3.1) to Pseudomonas aeruginosa (mean 8 x 10(8) cfu.mL-1: SEM 2.4). All non-typeable H. influenzae isolates recovered were beta-lactamase negative and sensitive to a range of antibiotics. Several biotypes and outer membrane protein profiles were observed, with no apparent association between these two phenotypic characteristics. The study showed that large numbers of non-typeable H. influenzae are often present in sputum from adult patients with CF. Further longitudinal studies of outer-membrane protein profile analysis are required to determine the dynamics of non-typeable H. influenzae colonization in individual patients and the clinical significance.
Article Reference Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae.
To evaluate the rate of bacteriologic failure of amoxicillin-clavulanate in the treatment of acute otitis media (AOM) and to identify the risk factors associated with failure.
Article Reference Antimicrobial therapy issues facing pediatricians.
In the field of infectious diseases, the emergence of new pathogens or old diseases in newly recognized forms; changing virulence of pathogens; changing patterns of antimicrobial susceptibility; new diagnostic techniques, drugs or vaccines; changing concepts of chemoprophylaxis; controversies about medical vs. surgical techniques; and the challenge of care of children with infectious diseases within new guidelines of managed care are recently identified areas of change. The increased resistance of Streptococcus pneumoniae to many commonly used antimicrobials and the increased proportion of beta-lactamase-producing nontypable Haemophilus influenzae and Moraxella catarrhalis concern many practitioners. The decreased antibiotic susceptibility of S. pneumoniae is a relatively new phenomenon in the United States. Optimal therapy for mild, moderate or severe pneumococcal disease is dependent on current local susceptibility patterns. Group A streptococci are uniformly susceptible to readily achieved concentrations of all penicillins and cephalosporins. However, recent clusters of cases of rheumatic fever, increased recognition of toxic shock syndrome and bacteremic and localized severe pneumococcal disease have increased concern about the changing ecology of the Streptococcus and the implications for therapy. Finally recognition that many children with acute bacterial otitis media have resolution of disease without use of antimicrobial agents has led to more rigorous study designs for evaluating new drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Article Reference Effect of oral antibiotics on nasopharyngeal colonization with nontypable Haemophilus influenzae.
Article Reference Prospective epidemiological study of invasive Haemophilus influenzae disease in adults.
The incidence and characteristics of invasive Haemophilus influenzae disease were studied in 43 adult patients admitted to the acute care hospitals in El Vallés County (Barcelona, Spain) between January 1987 and June 1992. The annual incidence of Haemophilus influenzae disease was 1.2 per 100,000 inhabitants. Pneumonia occurred in 24 patients, meningitis in five, intraabdominal infections in three, obstetric infections in two, epiglottitis in two and cellulitis in one. In six patients the source of infection was unknown. Ten (23%) of the infections were hospital acquired. Underlying conditions were diagnosed in 30 (70%) patients. Nontypeable Haemophilus influenzae strains predominated in all adult age groups. Sixty-one percent of type b and 34% of nontypeable strains were ampicillin resistant (p = 0.08). Multiple antibiotic resistance was also high among type b (53%) and nontypeable (18%) strains. The mortality rate was significantly higher in patients with pneumonia, bacteremia from an unidentified focus or shock at presentation.
Article Reference Antimicrobial susceptibility of nasopharyngeal isolates of potential pathogens recovered from infants before antibiotic therapy: implications for the management of otitis media.
Antimicrobial susceptibility was determined for strains of Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis recovered from the nasopharynxes of children followed from birth. The bacteria tested were the first potential pathogens isolated from each child before any treatment with antibiotics. Minimal inhibitory concentrations of commonly used oral antibiotics demonstrated the following overall rates of resistance for (1) S. pneumoniae: penicillin 1.2% (intermediate susceptibility 4.8%), trimethoprim-sulfamethoxazole 20%; (2) nontypable H. influenzae: ampicillin 32%, cefaclor 17%; (3) M. catarrhalis: ampicillin 90%, trimethoprim-sulfamethoxazole 19%. Antibiotic regimens used for treatment of otitis media may have to be evaluated in light of changing antibiotic susceptibilities.
Article Reference Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics.
We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture. Adenoid tissue was embedded in agar so that only the mucosal surface was exposed. Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h. The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM). Bacterial viable counts after 24 h were not significantly different in all organ cultures. Compared with uninfected controls at 24 h, infection with NTHi caused significant (p < 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites. TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage. In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p < 0.05). We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.
Article Reference Sinusitis in children.
Upper respiratory tract infection and allergic inflammation are recognized as the important risk factors for acute sinusitis, with upper respiratory tract infection being most common. In children with acute or chronic sinusitis, the respiratory symptoms of nasal discharge, nasal congestion and cough are usually prominent. Radiography has traditionally been used to determine the presence or absence of sinus disease. The radiographic findings most diagnostic of bacterial sinusitis are diffuse opacification, mucous membrane thickening or an air-fluid level. The predominant organisms include Streptococcus pneumoniae, Branhamella catarrhalis and nontypable Haemophilus influenzae. Several viruses including adenovirus and parainfluenzae have also been recovered. Clinical improvement is prompt in nearly all children treated with an appropriate antimicrobial agent.
Article Reference Neonatal sepsis due to nontypable Haemophilus influenzae.
From August 1980 through July 1984, 19 neonates had sepsis due to Haemophilus influenzae. Onset of disease occurred within 48 hours after birth of all the neonates. One neonate was born at term and 18 were born prematurely, including seven neonates born before 28 weeks' gestation. Eight neonates and one fetus died, six of them within 24 hours of birth. Acute chorioamnionitis was present in the placentas. Those neonates with the most severe placental inflammation survived while all of those who died had moderate or only mild chorioamnionitis. Acute villitis was noted in the placentas of three neonates who died. Respiratory distress syndrome (in 15 neonates) and pneumonia (in 15 neonates) were noted in 18 liveborn patients. Nine mothers had fever, six of them with genitourinary infections and one with septicemia due to H influenzae. All isolates of H influenzae were submitted for serologic typing and none were typable. In 14 cases, isolates were biotyped yielding eight with biotype II, four with biotype III, and one each with biotypes IV and V. Neonatal sepsis due to nontypable H influenzae is now nearly as common as sepsis due to group B Streptococcus. Both organisms produce diseases with many features in common, especially fulminant courses with respiratory distress and pneumonia, and often have a fatal outcome.
Article Reference In-vitro activity of imipenem against 100 strains of serotype b and nontypable Haemophilus influenzae, including strains resistant to ampicillin, chloramphenicol or both.
Imipenem, along with ampicillin, chloramphenicol, ceftazidime, aztreonam and ceftriaxone were tested against 100 clinical isolates of Haemophilus influenzae. Eighty-eight of the isolates were serotype b, 35 isolates were beta-lactamase producers, and five isolates were chloramphenicol resistant. Inoculum densities of 1 X 10(3), 1 X 10(5) and 1 X 10(8) cfu/ml were tested for all isolates. MIC90s and MBC90s at the two lower inoculum densities for imipenem, ceftazidime, aztreonam and ceftriaxone were in the susceptible range for all categories of isolates tested. Imipenem, ceftazidime and aztreonam displayed elevated MBC90s at the high inoculum density. The effect of the high inoculum density upon the ceftriaxone MBC90 was below the level of detection afforded by the study design.
Article Reference Bacteremia due to nontypable Haemophilus influenzae&ndash;three cases in a community hospital.
Nontypable Haemophilus influenzae is a normal inhabitant of the upper respiratory tract and a common pathogen in diseases limited to mucosal surfaces. Nontypable H. influenzae has only occasionally been reported to cause invasive disease locally or systemically. In a period of two years, three patients of 17 with positive blood cultures for H. influenzae were found to have nontypable strains, two of which were resistant to ampicillin. The presumed sites of entry were an oral mucosal lesion, sinus mucosa, and female genital tract. All three patients responded rapidly to antibiotics to which their isolates were susceptible.
Article Reference Relationship with original pathogen in recurrence of acute otitis media after completion of amoxicillin/clavulanate: bacterial relapse or new pathogen.
We sought to determine whether recurrent acute otitis media (rAOM) occurring within 30 days of amoxicillin/clavulanate treatment was caused by bacterial relapse or new pathogens.
Article Reference ``Affect of anaerobiosis on the antibiotic susceptibility of H. influenzae''.
Haemophilus influenzae is a human-restricted facultative anaerobe which resides mostly in the oropharynx. The majority of isolates recovered from the throat are unencapsulated commensals (NTHi), but depending on host susceptibility they cause bronchitis, otitis media and on occasion bacteremia and meningitis. Because of the variable oxygen availability in the various niche permitting bacterium replication, the organism must thrive in well oxygenated surfaces, such as pharyngeal epithelium to anoxic environments like the bottom of a Biofilm and in airway mucus. Other reports indicate that H. influenzae use aerobic respiration, anaerobic respiration and fermentation to generate ATP. To gain insight in to the activity of several classes of antibiotics against five well-characterized unencapsulated H. influenzae in room air, in 5% CO2 and under strict anaerobiosis. We also tested for the role of oxidative killing by all cidal antibiotics.
Article Reference Fulminant pneumonia caused by nontypable haemophilus influenzae.
Article Reference Bactericidal activity of garenoxacin against in vitro biofilm formed by nontypeable Haemophilus influenzae.
Using β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) and β-lactamase-negative ABPC-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) strains isolated from otological patients, colony biofilm was prepared on membrane filter substrates. Bactericidal activities of garenoxacin (GRNX), levofloxacin (LVFX), cefditoren (CDTR), and clavulanic acid/amoxicillin (CVA/AMPC) were examined by counting viable cells after drug exposure to biofilm cells for 6 and 24 h and by observation under a scanning electron microscope (SEM). After exposure of biofilm to the 100-fold MIC of GRNX or LVFX for 24 h, GRNX and LVFX showed potent bactericidal activity (∆log10 CFU/ml, ≥5.1). In this case, the drug-exposure AUC, exposure concentration × 24 μg h/ml, was 64-128 % for GRNX and 121 % for LVFX of free AUC at the clinical dosage in humans, respectively. CDTR and CVA/AMPC at 100-fold MIC exhibited little bactericidal activity against biofilm cells. Under an SEM, after exposure of BLNAS and BLNAR biofilms to GRNX or LVFX, most of the biofilm matrices were transformed. Quinolones such as GRNX show potent bactericidal activity against biofilm-forming NTHi at the usual clinical dosage.
Article Reference Clinical and molecular epidemiology of haemophilus influenzae causing invasive disease in adult patients.
The epidemiology of invasive Haemophilus influenzae (Hi) has changed since the introduction of the Hi type b (Hib) vaccine. The aim of this study was to analyze the clinical and molecular epidemiology of Hi invasive disease in adults.
Article Reference Antibodies directed against integration host factor mediate biofilm clearance from Nasopore.
Intranasal resorbable packing, such as Nasopore, is commonly used during sinus surgery despite a paucity of evidence that demonstrates clinical benefit. We theorized that Nasopore supports bacterial growth and biofilm formation. The DNABII family of bacterial nucleic acid binding proteins stabilizes the extracellular polymeric substance of the biofilm, thus protecting bacteria from host defenses and traditional antibiotics. We tested the hypothesis that use of anti-IHF antibodies in conjunction with antibiotics would enhance biofilm eradication from Nasopore.
Article Reference Genetic diversity of the ftsI gene in β-lactamase-nonproducing ampicillin-resistant and β-lactamase-producing amoxicillin-/clavulanic acid-resistant nasopharyngeal Haemophilus influenzae strains isolated from children in South Korea.
Haemophilus influenzae frequently colonizes the nasopharynx of children and adults, which can lead to a variety of infections. We investigated H. influenzae carriage in the nasopharynx of 360 children, in terms of (1) the prevalence of strains with decreased susceptibility, and (2) the presence of amino acid substitutions in PBP3. One hundred twenty-three strains were isolated (34.2%, 123/360), 122 of which were classified as nontypable H. influenzae (NTHi). Of these, β-lactamase-nonproducing ampicillin-susceptible strains accounted for 26.2%, β-lactamase-producing-ampicillin-resistant strains for 9.0%, β-lactamase-nonproducing ampicillin-resistant (BLNAR) strains for 40.2%, and β-lactamase-producing amoxicillin-/clavulanic acid-resistant (BLPACR) for 24.6%, respectively. Pulsed field gel electrophoresis (PFGE) patterns were so diverse that they were clustered into 41 groups. The amino acid substitutions in the transpeptidase domain (292 amino acids) of ftsI in BLNAR isolates showed that group IIb accounted for 30.6%, IIc for 8.2%, IId for 16.3%, III for 32.7%, and the others for 12.2%. Moreover, groups IIb (56.7%; 17/30) and III (23.3%; 7/30) were prevalent among BLPACR strains. They were subclassified into more diverse sequence subtypes by analysis of the entire PBP3 (610 amino acids). Groups IIb, IIc, IId, and III exhibited 13, four, six, and four sequence subtypes, respectively. Such a genetic diversity is likely indicative of significant potential for decreased antimicrobial susceptibility in nasopharyngeal-colonizing NTHi strains.
Article Reference Effect of low-intensity focused ultrasound on the middle ear in a mouse model of acute otitis media.
We hypothesized that low-intensity focused ultrasound (LIFU) increases vessel permeability and antibacterial drug activity in the mouse middle ear. We determined appropriate settings by applying LIFU to mouse ears with the external auditory canal filled with normal saline and performed histologic and immunohistologic examination. Acute otitis media was induced in mice with nontypable Haemophilus influenzae, and they were given ampicillin (50, 10, or 2 mg/kg) intraperitoneally once daily for 3 days with or without LIFU (1.0 W/cm(2), 20% duty cycle, 30 s). In the LIFU(+) groups receiving the 2- and 10-mg/kg doses, viable bacteria counts, number of inflammatory cells and IL-1β and TNF-α levels in middle ear effusion were significantly lower than in the LIFU(-) groups on the same doses. Severity of AOM also tended to be reduced more in the LIFU(+) groups than in the LIFU(-) groups. LIFU application with antibiotics may be effective for middle ear infection.