Prospective Evaluation Of Protected Alveolar Lavage (PAL) Staphylococcus Aurues Resistance Patterns

Hospital acquired pneumonia (HAP) is the second-most common nosocomial infection in hospitals and the most common in the intensive care unit1. Mortality for HAP exceeds 20%2. Although mechanical ventilation is the greatest risk factor and increases the risk of dying from HAP, the organisms responsible for causing pneumonia in a given ICU are the same regardless of whether patients are intubated3.

Staphylococcus aureus has become the leading pathogen responsible for hospital-acquired pneumonia (HAP) and is responsible for about 20% of cases4. Staphylococcus aureus may be either sensitive or resistant to oxacillin/methicillin. Oxacillin resistance rates are increasing nationwide and the average rate of resistance to oxacillin currently exceeds 52% nationwide5. While these "MRSA" isolates at UK represent only 47% of all staph aureus isolates, rates of methicillin resistant staphylococcus aureus (MRSA) may approach 80% in some institutions (unpublished observation).

Presence or absence of risk factors for MRSA determines whether or not MRSA drug therapy is used7. If a patient is thought to have pneumonia and they possess risk factors for MRSA, then antimicrobial therapy active against MRSA will be used empirically and "de-escalated" if objective culture data does not demonstrate MRSA. Empiric or culture-based therapy for MRSA HAP includes one of the following: 1) the glycopeptide vancomycin or 2) the oxazoladinone linezolid (Zyvox®). Antimicrobials with activity against MRSA but who do not currently have licensed indication for use in HAP include: 3) the glycylcycline, tigecycline (Tygacil®) and 4) the streptogramin, quinupristin-dalfopristin (Synercid®).

Vancomycin is the primary antimicrobial choice for MRSA HAP worldwide. Vancomycin is relatively inexpensive in per-dose pricing, generally effective and has a favorable safety profile. However, staph aureus isolates which are incompletely sensitive or even resistant to vancomycin have been reported8. These vancomycin-intermediately sensitive staph aureus (VISA) and vancomycin-resistant staph aureus (VRSA) isolates are rare but increasing in prevalence9. Since the first report of VISA in the United States in 1999, other reports have documented the existence of staph aureus isolates with incomplete sensitivity to vancomycin, termed as vancomycin "heteroresistance"9.

Heteroresistant vancomycin-intermediate sensitive staph aureus (hetero-VISA, hVISA, hGISA) isolates are those in which the prevalent colonies are vancomycin susceptible but in which some of the isolates demonstrate phenotypes which are intermediate or resistant to vancomycin9. Hetero-VISA has been proposed as an etiology for vancomycin treatment failure in some patients. These hetero-VISA isolates may exhibit vancomycin-susceptibility when analyzed by automated testing because automated systems are incapable of identifying rare hetero-VISA colony forming units (CFU's) within single large inoculums10. Without plating and more detailed testing, the true incidence of hetero-VISA isolates may be underestimated. No large direct comparison of automated and non-automated MRSA isolate sensitivities to vancomycin has been reported. This investigation seeks to determine the prevalence of hetero-VISA in sputum isolates of MRSA in a major tertiary referral center and define the sensitivity of automated testing.