Ventilator-acquired pneumonia (VAP) is a major complication in intubated and mechanically ventilated patients. Its consequences include increases in length of stay, health costs, antibiotic consumption, and in crude and attributable mortality. Due to the systematic application of bundles to prevent VAP in recent years, its incidence has fallen below six cases per 1000 days of mechanical ventilation [1,2].
Nosocomial pneumonia in the ICU can be divided into VAP and hospital-acquired pneumonia (HAP). Most of our knowledge of HAP in nonintubated patients has been extrapolated from VAP, which has been thoroughly investigated; having focused so intensively on VAP for many years, we have probably neglected nonventilated HAP acquired or admitted to the ICU. Together, the two entities can be termed ‘ICU-Acquired Pneumonia (ICUAP).’ In a systematic prospective search of cases of ICUAP at six different ICUs at a university tertiary hospital, we found that VAP accounted for 60% of cases of ICUAP, and HAP 40% . These figures emphasize the importance of nonventilated HAP  in the ICU. When nonventilated HAP requires mechanical ventilation, mortality is even higher than in VAP. In a docket document , the Food and Drug Administration (FDA) stressed the importance of HAP, HAP requiring ventilation and VAP. In fact, the 28-day mortality of these three different nosocomial categories varies: low for HAP, intermediate for VAP and the highest for HAP requiring mechanical ventilation. This information is likely to be of crucial importance for future RCTs.
The present issue of Current Opinion of Critical Care is devoted to the new concept of ICUAP. In the first chapter by Ferrer and Torres (pp. 325–331), the epidemiology of ICUAP is reviewed. As noted above, 30–40% of ICUAP are HAP and 50–60% VAP. With the increased use of noninvasive mechanical ventilation and high-flow oxygen systems, the number of intubated patients is falling. We now see more and more patients who are very sick but do not undergo intubation, and who frequently present risk factors for acquiring HAP.
The article by Chastre et al. (pp. 332–338) and article by Ranzani et al. (pp. 339–346) deal with microbial cause and its diagnosis, comparing HAP vs. VAP. The literature on this point is limited because of the difficulty of obtaining good quality respiratory samples in nonintuabted patients, but it seems that HAP in the ICU presents a similar microbiology to VAP. There is a need for good bronchoscopic studies in HAP patients to establish its microbial cause.
Conceptually, and according to the new guidelines [1,2], the different types of microorganisms that might cause HAP or VAP, and especially multi drug resistant microorganisms (MDR)/extended drug resistant microorganisms (XDR) or pan drug resistant microorganisms (PDR) microorganisms, are associated with a variety of clinical risk factors. In an era in which the majority of treatments for ICUAP are still empirical, precise information on the risk factors for MDR/XDR/PDR microorganisms is very important, as discussed in the article by Bassetti et al. (pp. 385–393).
As mentioned above, the IDSA/ATS and International European Guidelines were published in 2016 and 2017, respectively [1,2]. The differences between the two sets of guidelines are reviewed in the article by Martin-Loeches et al. (pp. 347–352). The main differences lie in the sampling and culturing of respiratory secretions (distal quantitative vs. proximal qualitative), risk factors for MDR/XDR/PDR microorganisms, duration of antibiotic treatments, and the use of biomarkers.
One of the most important issues is antibiotic treatment, which is reviewed in the article by Niederman (pp. 353–360). Overall, given the information available on HAP, there should not be many differences in the approach to the treatment of HAP and VAP in the ICU; the risk factors described for MDR/XDR/PDR microorganisms are the same for HAP as for VAP. However, studies that try to associate MDR/XDR/PDR microorganisms are much more frequent in VAP. Treatment duration, when the initial antibiotic is appropriate and when there are no complications of pneumonia, should not exceed 8–10 days. This is an important concept that has changed recently with the application of the stewardship programs. The international guidelines  propose an empirical treatment algorithm that is described in this chapter and is based on the presence or absence of two or more risk factors for MDR/XDR/PDR microorganisms, a probability of dying of more than 15% and the presence or absence of septic shock. In each of these situations dual or triple initial therapy (two antipseudomonal with anti MRSA) is recommended. This algorithm needs prospective validation.
Biomarkers, particularly C-reactive protein and Procalcitonin, are extensively used in the monitoring of treatment of severe infections in the ICU. However, the recent international guidelines  on HAP and VAP do not recommend their use in order to shorten antibiotic treatments when the initial treatment is appropriate and the patient presents good clinical evolution. However, there are situations in which biomarkers may guide the antibiotic duration, such as inappropriate initial treatment, immunosuppression, pulmonary abscess or empyema and the use of second-line antibiotics such as colistin, fosfomycin or tigecycline. All these issues are reviewed in depth in the chapter on biomarkers by Luna and Dianti (pp. 361–369).
In the last 10 years, considerable efforts have been made to prevent VAP. The application of bundles (combination of effective methods of VAP prevention) has helped to reduce the incidence of VAP, as commented above. In HAP, on the other hand, the physiopathology, incidence and risk factors have not been well studied and its prevention has been neglected, which is reviewed in the article by Lyons and Kollef (pp. 370–378). A great deal remains to be done: probably, however, the use of very simple interventions such as raising the head from the bed, and the administration of special diets to avoid aspiration of gastric contents or food into the lower airways could reduce the incidence of HAP. There is a clear need for interventional studies in this field.
Finally, the article by Talbot (pp. 379–384) compares the views of the two main regulatory agencies [FDA and European Medicines Agency (EMA)] on the execution of Randomized Controlled Trials (RCTs) for antibiotics. The FDA is much more aware of the concept of ICU-acquired pneumonia than the EMA: the FDA's most recent recommendations , in which the main end-point is any cause 28-day mortality, recognize the differences in mortality between HAP, HAP requiring mechanical ventilation and VAP.
In summary, the concept of ICUAP (HAP and VAP) needs to be implemented in the control of respiratory infections in the ICU. Nosocomial pneumonia in the ICU does not only include VAP. Measures of quality control in the ICU should implement this new concept of ICUAP. In addition, future RCTs (especially those dealing with new antibiotics and prevention) need to include and stratify both entities.
I want to thank Mrs Elisabeth Sancho for her secretarial assistance.
Financial support and sponsorship
This work is funded by CIBERES and Icrea academia Award from Generalitat de Catalunya.
Conflicts of interest
Advsiory board or lectures: Pfizer, MSD, Roche, Bayer, Polyphor, Astra-Zeneca.
1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63:e61–e111.
2. Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 2017; 50:3.
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