Haemophilus influenzae infection resistance

Levofloxacin (1), the levo-isomer or the (5)-enantiomer of ofloxacin, received FDA approval in 1996 (Fish, 2003 Hurst et al., 2002 Mascaretti, 2003 Norrby, 1999 North et al., 1998). The initial approval covered community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, uncomplicated skin and skin structure infections, acute pyelonephritis, and complicated urinary tract infections (North et al., 1998). Four years later, the levofloxacin indication list grew to include community-acquired pneumonia caused by penicillin-resistant Streptococcus pneumoniae. In addition, in 2002, nosocomial (hospital-acquired) pneumonia caused by methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Kliebsella pneumoniae, and Escherichia coli was added (Hurst et al., 2002). Finally in 2004, LVX was approved as a post-exposure treatment for individuals exposed to Bacillus anthracis, the microbe that causes anthrax, via inhalation (FDA, 2004). 

Rifampin is used in a variety of other clinical situations. An oral dosage of 600 mg twice daily for 2 days can eliminate meningococcal carriage. Rifampin, 20 mg/kg/d for 4 days, is used as prophylaxis in contacts of children with Haemophilus influenzae type b disease. Rifampin combined with a second agent is used to eradicate staphylococcal carriage. Rifampin combination therapy is also indicated for treatment of serious staphylococcal infections such as osteomyelitis and prosthetic valve endocarditis. Rifampin has been recommended also for use in combination with ceftriaxone or vancomycin in treatment of meningitis caused by highly penicillin-resistant strains of pneumococci. 

Disease that is segmental or lobar in its distribution is usually caused by Streptococcus pneumoniae (pneumococcus). Haemophilus influenzae is a rare cause in this group, although it more often leads to exacerbations of chronic bronchitis and does cause pneumonia in patients infected with HIV. Benzyl-penicillin i.v. or amoxicillin p.o. are the treatments of choice if pneumococcal pneumonia is very likely alternatively, use erythromycin/clarithromycin in a penicillin-allergic patient. Seriously ill patients are best given benzylpenicillin (to cover the pneumococcus) plus ciprofloxacin (to cover Haemophilus and atypical pathogens). Where penicillin-resistant pneumococci are prevalent, i.v. cefotaxime is a reasonable best guess choice. 

An area of increasing concern and clinical importance is the increasing macrohde resistance that has been reported over the last several years with some of the common pathogens, particularly Streptococcus pneumoniae, group A streptococci, and Haemophilus influenzae, and may result in failure of therapy of pneumonia, phar5mgitis, and skin infections (54). High rates of resistance of several groups of streptococci to macrohdes have been reported from all parts of the world (55-64). 

Thomsberry C, Sahm DF, Kelly LJ, et al. Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States Results from the TRUST surveillance program, 1999—2000. Qin Infect Dis 2002 34(suppl 1) S4-16. 

It is believed that the lung infection results from impaired mucus clearance followed by colonization of bacteria in the mucus. The bacteria elaborate a number of toxins, polysaccharides, and enzymes including proteases, elastases, and exotoxin A, which may stimulate the production of additional mucus and further contribute to airway obstruction (Sam et al., 1980 Adler et al., 1983). Pseudomonas aeruginosa and Staphylococcus aureus are the most commonly found bacteria in the lungs of patients with CF, but Klebsiella, Esherichia coli, streptococci, and Haemophilus influenza can also be found. Of particular interest is the observation that mucoid strains of infectious bacteria, which are more pathogenic than nonmucoid strains, are most commonly found in patients with CF (Reynolds et al., 1975, 1976). The mucoid strains are also more resistant to phagocytosis by alveolar macrophages and are impermeable to antibiotics because of their mucoid coats. Thus treatment of pulmonary infections in patients with CF can be unusually difRcult. 

Cefuroxime (35) is effective against community-acquired pneumonia in which ampicillin-resistant Haemophilus influenzae is the probable etiologic agent. Cefoxitin (23) is used to treat mixed aerobic—anaerobic infections including pelvic infections, intra-abdominal infections, and nosocomial aspiration pneumonia. Cefonicid (31), because of its long half-life has been used in a once-a-day regimen to treat a variety of mild to moderate infections including community-acquired pneumonias, urinary tract infections, and infections of the skin and soft tissue (132,215). 

Infections in cystic fibrosis are often due to Staphylococcus aureus, Haemophilus influenzae or Pseudomonas aeruginosa. Infecting organisms need to be identified so that the most appropriate antibiotics can be used. Antibiotics used to treat respiratory infections in cystic fibrosis commonly include ciprofloxacin, erythromycin, flu-cloxacillin and amoxicillin. However, specialist individual therapy is essential for maximum benefit to the patient and avoidance of the development of resistant strains of bacteria. 

Children are most susceptible to ear infections from antibiotic-resistant strains of Haemophilus influenzae, Staphylococcus aureus. Streptococcus pneumoniae, and Branhamella catarrhalis. The above treatment plan has been found highly effective for treating such infections. 

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