Severe community-acquired Enterobacterpneumonia: a plea for greater awareness of the concept of health-care-associated pneumonia

Haemophilus influenzae, Klebsiella pneumoniae and Escherichia coli are the most common aetiological agents of community-acquired pneumonia (CAP) caused by Gram-negative bacteria (GNB) [1, 2]. Epidemiological monitoring of CAP was started in 2002 in our intensive care unit (ICU) and revealed an increase in occurrence of severe Enterobacter CAP (EnCAP) from 2002 to 2005. No specific reference to Enterobacter spp. is made in CAP studies [3, 4], except for their low incidence in one recent study [5]. The primary aim of this study was to describe the characteristics of EnCAP, particularly to determine their specific characteristics in comparison with CAP due to common bacteria. This comparison included the presence of criteria for health-care-associated pneumonia (HCAP) described since 2005, i.e. after completion of EnCAP cases. HCAP refer to a new category of pneumonia apparently developing in the community with the particularity to apply to patients who have recently interfaced with the health care system [6, 7]. Bacteria responsible for HCAP can share the same susceptibility profile than hospital-acquired bacteria. The awareness of these criteria would then potentially improve the adequacy of empirical treatment and the prognosis of the pneumonia. In our study, we tested the hypothesis that it would have improved the specific prognosis of EnCAP.

During the 3-year study period, 134 patients were admitted to our medical ICU from outside the hospital setting for microbiologically-documented severe pneumonia. Ten patients (7.5%) had EnCAP.

This study provides new insights into non-nosocomial Enterobacter pneumonia where previously published data are scarce. This type of pneumonia is severe and seems to develop in patients with serious comorbidities. Bouza et al. [15] performed a retrospective study of 50 cases of Enterobacter bacteraemia developing in the community and reported several results that are in agreement with our own conclusions: (i) a high prevalence of underlying comorbidities; (ii) severe clinical presentation; and (iii) high incidence of septic shock (30% in their study, 50% in ours) [15]. Broughton et al. [16] reported an original case of E. cloacae necrotizing CAP. In our study, a predominant alveolo-interstitial pattern was observed with no cavitation or abscesses. This was reported previously nearly 30 years ago in a reference radiographic study [17]. No single clinical or radiographic finding other than a lower leukocytosis was specific enough to consider this pathogen in pneumonia.

However, these results should not conceal another important study suggestion, that misclassifying pneumonia occurring outside the hospital setting as CAP rather than HCAP could have a number of consequences on outcome. A recent editorial highlighted the fact that HCAP criteria remained poorly identified, the majority of physicians persisting in the prescription of regimens consistent with CAP recommendations [18]. This should be particularly crucial in patients with severe pneumonia admitted to the ICU. In 2007, an extension of previously proposed criteria was proposed [11] and validated more recently [12]. Until and probably since 2005, patients presenting with pneumonia outside the hospital setting admitted to hospital or the ICU escaped these recommendations [18–20]. We sought to retrospectively seek for HCAP criteria because in our ICU we faced with an increase in incidence of pneumonia due to an unusual community-acquired bacterial species (i.e. Enterobacter sp.) before 2005. Moreover we observed that Enterobacter spp. were more frequent in epidemiological HCAP studies [11, 18, 19] than in CAP studies [3–5]. Indeed, patients received empirical antibiotic treatments designed to take into account typical CAP bacteria, but these antibiotics failed to treat most EnCAP episodes (80%). A delay in the improvement of EnCAP was observed in comparison with adequately treated CAP. Should HCAP criteria have been acknowledged, empirical antibiotics with broader spectrum would have been used and an improved prognosis would have probably occurred. In the EnCAP group, the most relevant criterion that led to the retrospective diagnosis of HCAP was a history of previous hospitalization. The recent proposition of extension to >1 year [11] confers the advantage of improving the negative predictive value of HCAP criteria in order to make physicians more confident about using antibiotics with activity limited to purely community flora. Extending the interval beyond 1 year would reduce the positive predictive value without further improving the negative predictive value, and broad-spectrum antibiotic treatment would then be used unnecessarily. Among the criteria for HCAP, a history of previous hospitalization or antibiotic treatment is less easy to retrieve than admission from a health-care facility, especially in the ICU where patients often cannot be questioned. Our study shows that history of previous hospitalization must be investigated thoroughly in patients presenting with non-nosocomial pneumonia, or HCAP will potentially be wrongly classified as CAP.

The high proportion (40%) of ESBL-producing Enterobacter spp. in our study was significant. The emergence of ESBL enterobacteriaceae (ESBLE) strains in the community has been described previously, particularly in Europe [21]. Known risk factors include diabetes, prior hospital admission and previous antibiotic use [22] which corroborate our results. Of note, aminoglycosides remain often effective against these strains. Whether ESBLE gastrointestinal carriage is due to selection by antibiotic treatment used in the community, or to prolonged nosocomial acquisition in the community, remains unclear. Oral third-generation cephalosporins are commonly used in outpatients in France. Third-generation cephalosporins are known risk factors for ESBLE carriage [23]. However, in a more recent study, nosocomial acquisition of ESBLE followed by prolonged digestive carriage prior to community-acquired infection was strongly suggested by genotypic analysis [24].

The small population size in our study is an important limitation. Any conclusions drawn from this study should be regarded with caution. Besides, one could argue that BAL also recovered Moraxhella catarrhalis in a patient from the EnCAP group. However, BAL is a highly specific method and Enterobacter sp. grew to a higher threshold than Moraxhella sp. (1.5 × 10⁶ CFU/mL vs 10⁴ CFU/mL). Moreover the empiric antibiotic treatment of this patient (i.e. coamoxiclav) covered Moraxhella sp. but not Enterobacter sp. explaining the delay in the improvement of clinical signs of CAP. Statistical results excluding this case were not modified. The study precludes any firm conclusions about the relationship between the delay in appropriate antibiotic therapy and its influence on outcome. The severity of the underlying illnesses could have played an independent role and only multivariate analysis would have provided a sounder insight into this complex relationship. However, it is now accepted that any delay in appropriate antibiotic treatment in patients with septic shock is associated with a worse outcome [25]. The design of our study does not answer the question as to whether the worse outcome of EnCAP compared to common CAP is due to antibiotic inappropriateness (i.e. noncompliance with HCAP concept) or to Enterobacter itself. Only a comparison between Enterobacter HCAP and EnCAP could answer this question. However, two studies have reported the absence of specific findings with Enterobacter sp. compared with other Gram-negative bacteria [1, 17]. Therefore, it suggests that only noncompliance with HCAP concept was responsible for this worse outcome. Finally, previous antibiotic treatment could not be assessed accurately in our patients as it was a retrospective study. Some of the patients in the EnCAP group could also have received antibiotic treatment in the previous months. However, as already suggested, this is not always easy to ascertain in the real-life management of severe pneumonia.

In conclusion, this study shows that intensive care and other physicians can be faced with severe EnCAP in patients with comorbidities. The study is a plea for a greater awareness of the HCAP criteria: to ignore them may lead to inappropriate antibiotic treatment. HCAP criteria, and particularly history of previous hospital admission, should be systematically and thoroughly investigated at the time of admission of such patients.