Emergence of MDR Pathogens

In the past decade, there has been a notable escalation of infections due to MDR strains in the community and healthcare institutions (2,19). Examples of MDR Gram-negative bacilli include K. pneumoniae and Escherichia coli with ESBL+, P. aeruginosa and Acinetobacter baumannii (4,20). There has also been a rapid increase in infections due to MDR Gram-positive cocci, such as S. pneumoniae, community-acquired (CA) and healthcare-associated (HA) MRSA, and vancomy-cin-resistant strains, such as VRE and S. aureus with intermediate resistance (VISA) or a smaller number of isolates that have high resistance (VRSA) (2).

Infections due to MDR pathogens may delay early initiation of appropriate antibiotic therapy, often increasing patient morbidity and mortality, and result in higher healthcare costs related to complications and increased length of hospital stay (4). MDR pathogens are more commonly isolated from patients with: chronic diseases, immunosuppression, prior antibiotic therapy, prior hospitalization, intensive care stay, or long-term healthcare facility admissions (4). Many of these patients are merely colonized with MDR bacteria and thus may be a reservoir for transmission to others, but have no evidence of infection. Antibiotic use increases the selection pressure for growth and spread of MDR pathogens by increasing the numbers of organisms, colonization, and environmental contamination (3). More recently, these concerns have been compounded by rapid emergence and spread of community-acquired MDR infections caused by S. pneumoniae and MRSA (21,22).

In Vitro Vs. In Vivo or Clinical Resistance

There has been a continued emergence of antibiotic resistance among numerous bacteria, mycobacteria, viruses, fungi, and parasites. Many bacterial resistance studies have focused primarily on trends toward greater in vitro resistance among different species of bacteria. In vitro or laboratory-related antibiotic sensitivities, as measured by MIC, represents the concentration of antibiotic required to prevent the growth of a selected inoculum of bacteria in a test tube or on an agar plate. The MIC thus represents the concentration of antibiotic that should be present for treating bacteremia, and does not account for penetration of the antibiotic into tissues, such as the central nervous system, lung, prostate, or bone (23). It is important to emphasize that such in vitro data may not be applicable to infections involving invasive devices, such as central venous or urinary catheters or endo-tracheal tubes that may have bacteria embedded in biofilm, impairing antibiotic penetration or reducing bacterial killing by phagocytic cells, antibodies, and complement (24).

UPPER RESPIRATORY TRACT INFECTIONS Tonsillopharyngitis

Group A streptococcus (GAS) is the most common cause of tonsillopharyngitis requiring antibiotic therapy (25). GAS is associated with both suppurative and nonsuppurative complications (26). Suppurative complications include local cellu-litis, abscess formation, myositis, fasciitis, otitis media, and sinusitis. Nonsuppura-tive complications include rheumatic fever, streptococcal toxic shock syndrome, and glomerulonephritis. Prevention of acute rheumatic fever is the principle goal of treatment, but antibiotic therapy also reduces severity and duration of symptoms, shortens the infective period, and reduces suppurative complications.

The literature on SCAT for tonsillopharyngitis is difficult to interpret, due to differences in study design, adherence issues, and inconsistent endpoints. Poor adherence to a 10-day regimen is probably the most common cause for treatment failure (27). In addition, the long-term sequelae of GAS infections remain of great concern.

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