Antibacterial drugs

Cephalosporins are semisynthetic b-lactam antibiotics that are structurally and pharmacologically related to penicillins, carbacephems (e.g., loracarbef), and cephamycins (e.g., cefotetan, cefoxitin). Cephalosporins generally are divided into 4 groups (“generations”) based on their spectra of activity. Cefaclor, cefadroxil, cefdinir, cefditoren pivoxil, cefpodoxime proxetil, cefprozil, ceftibuten, cefuroxime axetil, cephalexin, and cephradine also are used orally for the treatment of mild to moderate skin and skin structure infections caused by susceptible staphylococci or streptococci.

Commercially available tobramycin solution for oral inhalation is administered via nebulization in the management of bronchopulmonary Pseudomonas aeruginosa infections in cystic fibrosis patients 6 years of age or older. Use of tobramycin oral inhalation solution can be considered for suppressive therapy in cystic fibrosis patients colonized with Ps. aeruginosa if they are 6 years of age or older and have a forced expiratory volume in 1 second (FEV1) that is 25-75% of the predicted value. At baseline, the FEV1 in all study patients was 25-75% of the predicted value.

Streptomycin is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis. The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) currently recommend several possible multiple-drug regimens for the treatment of culture-positive pulmonary tuberculosis. These regimens have a minimum duration of 6 months (26 weeks), and consist of an initial intensive phase (2 months) and a continuation phase (usually either 4 or 7 months).

Neomycin sulfate is usually administered orally. In patients with hepatic encephalopathy who are unable to take oral medication, the drug has also been given as a retention enema.

IM and IV dosage are identical and should be based on an estimate of ideal body weight. The manufacturers state that dosage by all routes of administration should not exceed 1.5 g daily. A causal relationship between maintenance of certain peak or trough serum concentrations or other pharmacodynamic endpoints and clinical response or toxicity has not been established to date for aminoglycoside dosing regimens. However, in general, desirable peak serum concentrations of kanamycin for systemic infections are 15-30 mcg/mL and trough concentrations of the drug should not exceed 5-10 mcg/mL.

Amikacin is a semisynthetic aminoglycoside antibiotic. Amikacin sulfate is administered by IM injection or IV infusion. Dosage of amikacin sulfate is expressed in terms of amikacin and is identical for either route of administration.

Fluoroquinolones act by inhibiting bacterial topoisomerase IV and DNA gyrase, which are enzymes required for DNA replication, transcription, repair, and recombination. The exact nature of the interaction of quinolones with their target enzymes is not completely understood.

Earlier generations of fluoroquinolones (e.g., ofloxacin) had limited activity against some respiratory pathogens, such as S. pneumoniae. However, recent fluoroquinolone agents (so-called third-generation agents, or the “respiratory fluoroquinolones”) are active against a broad spectrum of gram-positive and gram-negative bacteria, including atypical organisms. Therefore, they are highly effective in RTIs.

The fluoroquinolones have proven to be one of the most commercially and clinically successful antibacterial classes for the treatment of acute exacerbations of chronic bronchitis.

Cephalosporins have traditionally been one of the most commonly used antibacterial classes for the treatment of respiratory tract infections. In recent years, drug development within this class has been limited owing to competitiveness, the lack of novel candidates, and high development costs relative to return. Cephalosporins differ widely in their spectrum of activity, susceptibility to β-lactamases produced by bacteria, and serum half-life. Dong-A pharmaceuticals in South Korea is developing DA-7101, indicated for the potential treatment of respiratory and urinary tract infections.