PICO questions and recommendations
| PICO question | Recommendations |
| Question 1: In intubated patients suspected of having VAP, should distal quantitative samples be obtained instead of proximal quantitative samples? | We suggest obtaining distal quantitative samples (prior to any antibiotic treatment) in order to reduce antibiotic exposure in stable patients with suspected VAP and to improve the accuracy of the results. (Weak recommendation, low quality of evidence.) |
| We recommend obtaining a lower respiratory tract sample (distal quantitative or proximal quantitative or qualitative culture) to focus and narrow the initial empiric antibiotic therapy. (Strong recommendation, low quality of evidence.) | |
| Question 2: Can patients suspected of having nosocomial pneumonia (HAP and VAP), who have early-onset infection and none of the classic risk factors for MDR pathogens, be treated appropriately if they receive a different and narrower spectrum empiric therapy than patients with late-onset infection and/or the presence of MDR risk factors? | We suggest using narrow-spectrum antibiotics (ertapenem, ceftriaxone, cefotaxime, moxifloxacin or levofloxacin) in patients with suspected low risk of resistance and early-onset HAP/VAP. (Weak recommendation, very low quality of evidence.) |
| Remarks: The risk of Clostridium difficile infections is increased with third-generation cephalosporins compared with penicillins or quinolones. The panel found it reasonable to consider as “low risk” patients without septic shock, with no other risk factors for MDR pathogens and those who are not in hospitals with a high background rate of resistant pathogens. However, the presence of other clinical conditions may make individuals unsuitable for this recommendation. The rate of resistant pathogens is highly variable across different countries, settings and hospitals. A prevalence of resistant pathogens in local microbiological data >25% is considered a high background rate (the rate of resistance in the ICU caring for the patient (not the hospital as a whole) is the relevant factor to consider). | |
| We recommend broad-spectrum empiric antibiotic therapy targeting Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing organisms, and, in settings with a high prevalence of Acinetobacter spp., in patients with suspected early-onset HAP/VAP who are in septic shock, in patients who are in hospitals with a high background rate of resistant pathogens present in local microbiological data and in patients with other (nonclassic) risk factors for MDR pathogens (see Question 3). (Strong recommendation, low quality of evidence.) | |
| The panel believes that tailoring antibiotic therapy to the susceptibility data of the aetiological pathogen once microbiological and clinical response data become available (day 3) represents good practice. (Good practice statement.) | |
| Question 3: When using initial broad-spectrum empiric therapy for HAP/VAP, should it always be with two drugs or can it be with one drug and, if starting with two drugs, do both need to be continued after cultures are available? | We recommend initial empiric combination therapy for high-risk HAP/VAP patients to cover Gram-negative bacteria and include antibiotic coverage for MRSA in those patients at risk. (Strong recommendation, moderate quality of evidence.) |
| Remarks: The panel finds it reasonable to consider as “high-risk HAP/VAP” patients who present HAP/VAP and either septic shock and/or the following risk factors for potentially resistant microorganisms: hospital settings with high rates of MDR pathogens (i.e. a pathogen not susceptible to at least one agent from three or more classes of antibiotics), previous antibiotic use, recent prolonged hospital stay (>5 days of hospitalisation) and previous colonisation with MDR pathogens. The rate of resistant pathogens varies widely across different countries, settings and hospitals. However, a prevalence of resistant pathogens in local microbiological data >25% represents a high-risk situation (including Gram-negative bacteria and MRSA). | |
| If initial combination therapy is started, we suggest continuing with a single agent based on culture results and only consider maintaining definitive combination treatment based on sensitivities in patients with extensively drug-resistant (XDR; i.e. susceptible to only one or two classes of antibiotics)/pan-drug-resistant (PDR; i.e. not susceptible to any antibiotics) nonfermenting Gram-negative bacteria and carbapenem-resistant Enterobacteriaceae (CRE) isolates. (Weak recommendation, low quality of evidence.) | |
| Remarks: The panel finds it reasonable to consider selected patients at low risk for MDR pathogens (see Question 2) and some patients at high risk for MDR pathogens for initial empiric monotherapy, if there is a single-antibiotic therapy that is effective against >90% of Gram-negative bacteria according to the local antibiogram. However, other clinical conditions, particularly severe illness or septic shock, may make individuals unsuitable for this recommendation. | |
| Question 4: In patients with HAP/VAP, can duration of antimicrobial therapy be shortened to 7–10 days for certain populations, compared with 14 days, without increasing rates of relapsing infections or decreasing clinical cure? | We suggest using a 7–8-day course of antibiotic therapy in patients with VAP without immunodeficiency, cystic fibrosis, empyema, lung abscess, cavitation or necrotising pneumonia and with a good clinical response to therapy. (Weak recommendation, moderate quality of evidence.) |
| Remarks: This recommendation also includes patients with nonfermenting Gram-negatives, Acinetobacter spp. and MRSA with a good clinical response. Longer courses of antibiotics may be needed in patients with inappropriate initial empiric therapy, and should be individualised to the patient's clinical response, specific bacteriological findings (such as PDR pathogens, MRSA or bacteraemia) and the serial measurement of biomarkers when indicated (see Question 6 and table 3). | |
| The panel believes that applying the rationale and recommendations used for VAP in nonventilated patients with HAP represents good practice. (Good practice statement.) | |
| We suggest against routine treatment with antibiotics for >3 days in patients with low probability of HAP and no clinical deterioration within 72 h of symptom onset. (Weak recommendation, low quality of evidence.) | |
| Remarks: The term “low probability of HAP” refers to patients with low Clinical Pulmonary Infection Score (CPIS) scores or a clinical presentation not highly suggestive of pneumonia (e.g. ≤6) at symptom onset and continuing up to 72 h. | |
| Question 5: In patients receiving antibiotic treatment for VAP or HAP, is bedside clinical assessment equivalent to the detection of serial biomarkers to predict adverse outcomes/clinical response at 72–96 h? | The panel believes that performing routine bedside clinical assessment in patients receiving antibiotic treatment for VAP or HAP represents good practice. (Good practice statement.) |
| Remarks: Clinical evaluation usually involves measurement of temperature, tracheobronchial secretion volume, culture and purulence assessment of tracheobronchial secretions, evaluation for chest radiograph resolution, white blood cell count, arterial oxygen tension/inspiratory oxygen fraction (PaO2 /FIO2), and calculation of one or more scores such as CPIS, ODIN (Organ Dysfunction and Infection System), SOFA (Sequential Organ Failure Assessment), SAPS II (Simplified Acute Physiological Score II) and APACHE II. | |
| We do not recommend routinely performing biomarker determinations in addition to bedside clinical assessment in patients receiving antibiotic treatment for VAP or HAP to predict adverse outcomes and clinical response at 72–96 h. (Strong recommendation, moderate quality of evidence.) | |
| Remarks: Biomarker determinations may include C-reactive protein (CRP), procalcitonin (PCT), copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP). Clinicians should take into consideration the availability, feasibility and costs of each biomarker before routine testing. | |
| Question 6: In patients with HAP with severe sepsis or VAP, can serum PCT be used to reduce the duration of antibiotic therapy, compared with care that is not guided by serial biomarker measurements? | We do not recommend the routine measurement of serial serum PCT levels to reduce duration of the antibiotic course in patients with HAP or VAP when the anticipated duration is 7–8 days. (Strong recommendation, moderate quality of evidence.) |
| The panel believes that the measurement of serial serum PCT levels together with clinical assessment in specific clinical circumstances (see table 3) with the aim of reducing antibiotic treatment duration represents good practice. (Good practice statement.) | |
| Question 7: In patients requiring mechanical ventilation for >48 h, does topical application of nonabsorbable antimicrobials (antibiotics or chlorhexidine) in the oropharynx (SOD) or in the oropharynx and intestinal tract along with intravenous antibiotics (SDD) reduce the risk of VAP occurrence and/or improve patient outcome compared with standard care? (Standard care being treatment dispensed in the ICU by the medical team in their usual manner) | The guideline panel decided not to issue a recommendation on the use of chlorhexidine to perform selective oral decontamination (SOD) in patients requiring mechanical ventilation until more safety data become available, due to the unclear balance between a potential reduction in pneumonia rate and a potential increase in mortality. (No formal recommendation.) |
| We suggest the use of SOD, but not SDD, in settings with low rates of antibiotic-resistant bacteria and low antibiotic consumption (where low antibiotic consumption in the ICU is <1000 daily doses per 1000 admission days). (Weak recommendation, low quality of evidence.) | |
| Remarks: Although establishing a cut-off value for low and high resistance settings is a dilemma, the committee felt that a 5% threshold was reasonable. |
VAP: ventilator-associated pneumonia; HAP: hospital-acquired pneumonia; MDR: multidrug-resistant; ICU: intensive care unit; MRSA: methicillin-resistant Staphylococcus aureus; APACHE II: Acute Physiology and Chronic Health Evaluation II; SDD: selective digestive decontamination.