We found that in a population of patients with nosocomial pneumonia enrolled in a large, international, randomized, double-blind trial of therapies for MRSA, the frequencies of potentially MDR gram-negative pathogens were similar among patients with pneumonia classified as HCAP, HAP, or VAP. This suggests that, as recommended in ATS/IDSA guidelines  empiric antibiotic regimens utilized for patients hospitalized with HCAP should be similar to those for HAP and VAP.
It is widely accepted that pneumonia occurring after initiation of mechanical ventilation should initially be treated with antibiotics active against MDR pathogens. The rationale is straightforward: ventilated patients are cared for in settings with high antibiotic utilization and often receive antibiotics for other reasons. Both factors contribute to the selection of MDR pathogens when pneumonia occurs. Epidemiologic data in turn provide empiric support for these recommendations [27, 28]. Though these rationales and supporting epidemiologic data are somewhat less compelling for pneumonias acquired in the hospital under circumstances other than mechanical ventilation, the extrapolation of VAP regimens to HAP patients has been widely recommended [1, 29, 30] and generally accepted.
In contrast, recommendations to use antibiotic combinations originally chosen for VAP for patients with HCAP have met with more controversy , with some arguing that the HCAP classification itself lacks utility . Our findings speak to both questions. Patients with HCAP were similar to those with HAP and VAP in several key respects: severity of illness; microbiology, particularly the frequency of potentially MDR pathogens; incidence of bacteremia; and short-term mortality. On the other hand, the higher burden of chronic conditions observed among HCAP patients in this study may justify its being a separate classification, particularly for investigators examining factors other than pathogen distribution.
Our study has several limitations. Most importantly, rather than a survey of incident pneumonias, our data derive from a population recruited because of its perceived MRSA risk. Investigators may have taken into consideration factors not accounted for in the collected data that differentiate enrolled patients from other patients with VAP, HAP, and HCAP; e.g. airway specimen gram stain results, history of MRSA colonization, and even infections and colonization of nearby patients. If study investigators intended to enroll patients with MRSA infection, they indeed succeeded, selecting a population with a prevalence of MRSA exceeding that commonly reported [2, 31–33]. We feel data from this study therefore should not be used to compare MRSA risk among pneumonia groups. Rather, our analysis focuses on the prevalence of potentially MDR gram-negative organisms, potential pathogens that the study was not seeking, and the agents under study do not treat. Distributions of potentially MDR gram-negative organisms were similar among patients with VAP, HAP, or HCAP and varied little with the presence or absence of MRSA.
That the study design should enhance recruitment of patients with gram-negative pathogens is certainly not obvious. Patients without MRSA were not permitted to complete the clinical trial, and investigator knowledge of certain specific gram-negative risk factors (gram stain results, colonization history, or local ecology) would likely discourage enrollment of patients with gram-negative infections. On the other hand, to the extent that investigators believed that risk factors for MRSA and MDR gram-negative pathogens are similar, efforts to enhance MRSA pneumonia recruitment might also have increased the prevalence of gram-negative pathogens in our sample. In either case, we have little reason to expect that such biases differed by pneumonia class. Our key finding thus seems robust: the likelihood of MDR gram-negative pathogens being present in HCAP is similar to that in HAP and VAP, pneumonias for which coverage of these organisms is widely accepted.
As is always the case in studies that do not obtain tissue to confirm the presence of pneumonia histopathologically, diagnoses and causative microbiology cannot be established with certainty . It is possible that in many cases potentially pathogenic bacteria were merely colonizers, particularly when multiple potential pathogens were found in the same patient. We know of no reason why this would be more likely in HCAP than in HAP or VAP. To the contrary, we suspect colonization is a more frequent phenomenon among patients with VAP, whose airways are instrumented. In any case, distinguishing true pathogens from colonizers in clinical practice is challenging; a commonly adopted strategy is therefore to treat all isolated organisms reasonably likely to be pathogens. Empiric regimens for HCAP should therefore be as broad in spectrum as those for HAP and VAP.
Geography may play an important role in our findings. HCAP patients were enrolled disproportionately in the United States. Possible interpretations include physicians outside the United States not recognizing patients with HCAP as being at risk for MRSA and so not considering them for enrollment; HCAP being more common in the United States than elsewhere; or investigator access to patients with HCAP varying by country. It seems clear that empiric antibiotics for HCAP in the United States should cover MDR pathogens. Given the possible differences in HCAP incidence across geographic regions, we would be hesitant to assume that the microbiology, and hence recommended treatments, should not also vary with location.