Streptococcus pneumoniae infections penicillin-resistant

Problems of cmtimicrobial resistance have burgeoned during the past decade in most coimtries of the world. Some resistant microbes are currently mainly restricted to patients in the hospitcil, e.g. MRSA, vancomycin-resistant enterococci (VRE), and coliforms that produce extended spectrum P-lactamases. Others more commonly infect patients in the community e.g. penicillin-resistant Streptococcus pneumoniae and multiply-resistant Mycobacterium tuberculosis. Evidence is accruing that the outcomes of infections with antibiotic resistant bacteria are generally poorer than those with... 

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). 

Due to its powerful specific activity against commonly isolated community-acquired respiratory tract pathogens [33,149-158], including penicillin-sensitive and -resistant Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus, Haemophilus spp., Moraxella catarrhalis and atypical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila and Klebsiella pneumoniae and anaerobic bacteria [159-162], moxifloxacin was developed as a respiratory tract anti-infective [163-168]. 

DalhoffA, etal. Penicillin-resistant Streptococcus pneumoniae review of moxifloxacin activity. Clin. Infect. Dis., 2001, 32 (Suppl. 1), S22-S29. 

Some streptococci have developed a different mechanism of acquired resistance to penicillin drugs. These bacteria have altered transpeptidases (also known as penicillin-binding proteins) that no longer bind penicillin, and thus peptidoglycan synthesis is not disrupted. This mechanism of resistance is found in Streptococcus pneumoniae. Estimates of penicillin-resistant S. pneumoniae in the United States range from 25% to 66%, including strains recovered from ocular and periocular infections. Many isolates of penicillin-resistant S.pneumoniae also are resistant to the cephalosporins, macrolides, and the older fluoroquinolones. Use of alternative antibiotics such as vancomycin is necessary for infections caused by penicillin-resistant isolates. 

Cefeclor is nsed to treat bacterial infections of the middle ear, limg, and urinary tract. Oral cefeclor can also be used to treat mild preseptal celluUtis. Parenteral administration of cefuroxime along with ampicillin/snlbactam is a recommended treatment for severe or imresponsive preseptal cellulitis (see Table 11-1). However, with the increase of penicillin-resistant isolates of Streptococcus pneumoniae, the effectiveness of empirically treating this condition with p-lactam dmgs needs to be carefully considered. 

Because of its potential toxicity, vancomycin is reserved for serious infections in which less toxic antibiotics are ineffective or not tolerated. Generally, vancomycin is administered intravenously because of poor intestinal absorption. It is the drug of choice for treating infections caused by methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae. Vancomycin has been used to treat enterococcal infections because of their resistance to the P-lactam antibiotics, but most enterococci are now also resistant to vancomycin. Oral administration of rancomycin is important for treatment of some gastrointestinal infections such as pseudomembranous colitis caused by C. difficile. 

Methicillin-resistant strains of Staphylococcus aureus and S. epidermidis and penicillin-resistant Streptococcus pneumoniae have been isolated from ocular infections. Therefore treatment of ocular infections caused by these organisms might require use of vancomycin for resolution. Vancomycin is also recommended for empiric intra-vitreal and topical therapy in bacterial endophthalmitis and for parenteral therapy in moderate to severe preseptal cellulitis (see Table 11-1). 

Others. Leoofloxacin (t) 7h) has greater activity against Streptococcus pneumoniae than ciprofloxacin and is used for respiratory and urinary tract infection. Moxifloxacin (t) 12 h) has strong anti-Gram-positive activity, and may prove useful for respiratory tract infections including those caused by atypical pathogens and penicillin-resistant Streptococcus pneumoniae. 

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. 

Moxifloxacin is an 8-methoxyquinolone with enhanced potency against important Gram-positive pathogens, notably Streptococcus pneumoniae (penicillin-resistant and penicillin-susceptible strains), and class activity against Gram-negative bacteria. Its activity is not affected by beta-lactamases. Moxifloxacin may therefore represent a promising alternative for treatment of respiratory tract infections (1). 

Fosfomycin is one of a few natural products containing a carbon-phosphorus (C— P) bond isolated from Streptomyces fradiae, Streptomyces viridochromogenes, and Streptomyces wedmorensis [73]. It was also isolated from Pseudomonas syringae and Pseudomonas viridiflava [74, 75], Fosfomycin is a highly effective antibiotic of low toxicity clinically utilized for the treatment of lower urinary tract infections [76] as well as methicillin-resistant [77] and vancomycin-resistant [78] strains of S. aureus. Moreover, fosfomycin is effective for the treatment of cephalosporin- and penicillin-resistant Streptococcus pneumonia [79] and ciprofloxacin-resistant E. coli [80], The antimicrobial activity of fosfomycin has been ascribed to the inactivation of UDP-GlcAAc-3-O-enolpyruvyltransferase (MurA), an essential enzyme that catalyzes the first committed step in the biosynthesis of peptidoglycan, the main component of the cell wall, by covalent alkylation of an active site cysteine [81]. 

In addition to S. pneumoniae, the viridans group of streptococci is also developing resistance to penicillin through the same mechanism, altered penicillin-binding proteins. In contrast, resistance has not developed in Streptococcus pyogenes, and both penicillins G and V are antibiotics of choice for systemic infections caused by this organism. 

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