General Approach to Treatment

Designing a therapeutic regimen for any patient with any type of pneumonia begins with three general categories of consideration:

1. Patient specific factors that will impact therapy

2. The top one to three organisms likely causing the infection, and resistance issues associated with each organism

3. The antimicrobials that will cover these organisms. The spectrum should not be too broad or narrow; they should penetrate into the site of infection and be the most cost effective.

Patient factors that need to be considered include age, renal function, drug allergies and/or drug intolerances, immune status (diabetes, neutropenia, or immunocomprom-ised host), cardiopulmonary disease, pregnancy, medical insurance and prescription coverage, and prior antibiotic exposure(s) (what agents and when).

The most common pathogens vary with the type of pneumonia, and they are listed in Table 71-1. M. pneumoniae lack a cell wall; therefore, ^-lactam antimicrobials have no activity against this organism. The atypical organisms have not changed in recent years with respect to antibiotic resistance. ^-lactamase production in H. influ-enzae has remained relatively steady over the last 5 to 10 years and the rate is approximately 35%26 S. pneumoniae has developed resistance mechanisms against many classes of antimicrobials and the mechanisms include:

• Alteration of the penicillin binding proteins (PBPs) inactivating ^-lactams

• Efflux or methylation of the ribosome inactivating macrolides

• Ribosome protection (tetM gene) inactivating tetracyclines

• Alteration of DNA gyrase or topoisomerase IV inactivating fluoroquinolones

Resistance to commonly prescribed antimicrobials such as the penicillins and mac-

rolides/azalides dramatically increased in the late 1980s through the mid- to late

1990s. Table 71-2 provides resistance information collected nationally from 1999

to 2007 using the Tracking Resistance in the US Today (TRUST) surveillance data-27

base. In 2007, the average national rate of resistance to penicillin and macrolides was approximately 13% and 32%, respectively. Susceptibility results alone do not account for clinical success or failures when treating pneumonia. Therefore, despite the 13% and 32% resistance to penicillin and macrolides, the clinical failure rate is less than this. Because CAP in the outpatient setting is treated empirically, establishing a meaningful clinical failure rate with any therapy is difficult to do. No studies have been performed that established a correlation between clinical failure rates with a particular antimicrobial agent and the percentage of resistant bacterial pathogens.

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