Impact of methicillin resistance on mortality in Staphylococcus aureus VAP: a systematic review

Athanassa Z, Siempos II, Falagas ME. Eur Respir J 2008;31:625–632.

Summary:

Under the leadership of Dr Falagas (one of the authors of this article), Athanassa and colleagues performed a systematic literature search and a meta-analysis to estimate the impact of methicillin resistance on mortality in ventilator-associated pneumonia (VAP). The authors hypothesised that comorbidities and adequate empiric therapy would independently enhance outcomes. This report is unique in several ways:

• Large sample size
• Control for severity-of-illness, age, therapy and comorbidities
• Majority of patients with VAP
• Microbiologically confirmed diagnosis
• Assessment of multiple process-of-care variables, such as timeliness and appropriateness of antibiotics, which have been shown to affect survival.

Most important limitations are well acknowledged by the authors, including variability in the case mix, diversity in diagnostic techniques, a lack of standardisation of the severity of illness, a lack of specification of dose and agent used for therapy, as well as the polymicrobial nature of the infection.

As one would predict, methicillin-resistant Staphylococcus aureus (MRSA) cases increased mortality compared with methicillin-sensitive S. aureus (MSSA) VAP, but the authors do not necessarily prove a causative relationship between methicillin resistance and excess lethality. Full details of the analysed studies, as well as the pooled meta-analysis are detailed in Figure 1*.

In a univariate analysis, the presence of MRSA was associated with increased age, the severity of illness and inadequate treatment, all of which were independently associated with a less favourable prognosis. The presence of outbreak and polymicrobial status of VAP were reported in 4 of 8 studies. One might presume that these differences in survival simply reflected the impact of other variables, or that findings may have been influenced by the largest study. However, the main findings did not change substantially at multivariate analysis or after exclusion of the above report.

Despite the above mentioned limitations, the authors of this meta-analysis confirm that MRSA pneumonia is of great clinical and health economic importance. Even though limited evidence exists to suggest that this association is not retained after adjustment for clinically significant confounding factors, this relationship does not appear to be causal but probably due to confounders, such as the adequacy of empiric therapy.

AIM core principles supported:

All 8 core principles proposed by AIM are supported in the current paper, with particular focus on the following 4 principles:

• Antibiotic choice: Empiric antibiotic regimens should be designed to cover the likely pathogens initially. The authors of this meta-analysis recognise the important role of MRSA in the ICU.
• Antibiotic choice: It is important to start with the appropriate empiric antibiotic first when treating nosocomial infections. The results of the analysis by Athanassa and colleagues emphasise that getting it right first time is key.
• Patient outcomes: Select the most appropriate antibiotic depending on the patient, risk factors, suspected infection and resistance. Again, age, severity-of-illness and comorbidities differed between MRSA and MSSA and also between studies. In essence, they reflect the AIM concept of focusing on patient outcomes.
• Resistance: The empiric antibiotic regimen should be based on likely susceptibility data.

Learning points:

• Methicillin resistance is associated with mortality among patients acquiring MRSA VAP.
• This association may not be causal, but is probably due to confounders, such as the severity of illness and the adequacy of empiric treatment.
• ‘Get it right first time’ is associated with increased survival.

*Permission to re-use has been given by European Respiratory Society Journals Limited