Although there are guidelines for the management of hospital-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP), and knowledge of the related diseases is increasing, their incidence is not decreasing. And at a high price.
Almost 10% of patients on mechanical ventilation (MV) develop VAP, and it is estimated that the mortality of patients with this pneumonia reaches 13%.
A survey of 183 hospitalized patients conducted in the US in 2014 revealed that HAP and VAP together are responsible for 22% of hospital-acquired infections. Hospitalizations for patients with VAP are longer and the cost of medical care is higher compared to patients without VAP.
In this work, the authors draw on the 2016 guidelines of the Diseases Society of America (IDSA) and the American Thoracic Society (ATS), as well as current literature.
| Terms |
> Pneumonia acquired in the hospital.
HAP is a pneumonia (lower respiratory tract infection verified by the presence of a new pulmonary infiltrate on imaging) that develops 48 hours after admission of non-intubated patients.
> Ventilator-associated pneumonia
VAP is the most common and fatal nosocomial infection in intensive care unit (ICU) patients. It is a pneumonia that develops after 48 hours in patients with endotracheal intubation. It is noted that, at the time of VAP onset, patients may have already been extubated.
> The term "healthcare-associated pneumonia" is no longer used
It should be noted that the term “healthcare-associated pneumonia” (NAAM) has been removed from the 2016 guidelines.
In the 2005 IDSA/ATS guidelines, HAP was defined as pneumonia developing in a person hospitalized for more than 48 hours in the past 90 days, or residing in a nursing home or extended care facility, or, are receiving home infusion therapy, home health care, wound healing, or are on chronic dialysis.
As patients who frequently interact with the healthcare system are suspected of being carriers of multidrug-resistant organisms, the recommended regimen for patients with HAP and VAP is the empirical one.
A systematic review and meta-analysis of 24 studies found that, in relation to HAP, these criteria do not reliably correlate with the presence of multidrug-resistant organisms.
Mortality from HAP was not associated with multidrug-resistant organisms, but rather with age and comorbidities.
Finally, the term HAP was adopted, to have minimal practical value in decision making regarding empirical antibiotic selection and overall prognosis.
Patients who had previously been diagnosed with NAAM should have been treated as carriers of community-acquired pneumonia (CAP), unless they had specific individual risk factors requiring empirical broad-spectrum antibiotic treatment.
| Aspiration is an important cause of NAH and VAP |
In addition to the importance of aspiration , it is worth noting that proton pump inhibitors and histamine 2 receptor blockers, by suppressing acid production, may allow nosocomial pathogens to colonize the oropharynx and endotracheal tube. and be sucked in. Specific risk factors for VAP, such as age, recent surgery, and admission for urological problems or cardiovascular failure, increase the risk of aspiration.
| The diagnostic challenge |
It can be difficult to make the diagnosis of HAP and VAP promptly, due to the paucity of diagnostic tests and a broad differential diagnosis for patients with increasing oxygen requirements, leukocytosis, and secretions. Respiratory deterioration accompanied by fever and productive cough, or following in-person aspiration or suspected in-hospital event, may suggest the development of pneumonia.
When rating systems such as those used to calculate the clinical score for pulmonary infection, intended to guide the management of CAP, the IDSA/ATS guidelines suggest the use of clinical criteria only for the management of CAP and VAP.
According to the guidelines, the diagnosis of HAP and VAP requires compliance with all of the following points:
• New pulmonary infiltrate on chest images
• Respiratory impairment
• Fever
• Productive cough
The absence of a new infiltrate significantly reduces the likelihood of VAP and may direct the clinician toward other causes of respiratory impairment, including pulmonary embolism.
| Non-invasive tests |
Once an infiltrate is observed and the cause of respiratory deterioration is presumed to be HAP or VAP, several noninvasive tests are recommended to isolate a pathogen and rapidly tailor empiric antibiotic treatment against the culprit organism.
> Blood cultures . Blood cultures are recommended for all patients diagnosed with HAP or VAP. 15% of patients with VAP are bacteremic, and up to 25% of blood cultures in this group demonstrate pathogens that reflect a secondary, nonpulmonary source of infection.
Therefore, blood cultures may be useful in identifying the pathogen responsible for HAP or VAP, especially if respiratory cultures are unrevealing, and also in informing the clinician about the presence of additional concomitant infections, unrelated to the respiratory tract. .
For example, Candida and Enterococcus species are not a known cause of pneumonia; Thus, detection of these pathogens in the bloodstream may direct the clinician to a different, previously unsuspected site of infection, such as catheter-related infection.
> Sputum culture . Culture is indicated in non-intubated patients with HAP and VAP who are able to produce a sufficient sample, characterized by fever without squamous cells in the Gram stain.
In patients who cannot produce an adequate sputum sample, semiquantitative samples obtained by noninvasive methods (e.g., endotracheal aspiration) are preferred over quantitative samples obtained by invasive methods, such as bronchoscopy and bronchial sampling. blind (mini-bronchoalveolar lavage) in an effort to reduce the cost and patient harm generated by invasive quantitative testing.
Quantitative tests may give false negative results if prior to collection, the patient received antibiotics, which may result in erroneous discontinuation of appropriate treatment.
On the other hand, in patients who were subjected to sampling, a lack of improvement in the mortality rate, length of stay in the ICU or MV has been observed. However, invasive sampling may be justified in patients who are immunocompromised or experience continued clinical deterioration despite appropriate antibiotics, with a negative noninvasive evaluation, given their improved diagnostic performance.
If invasive sampling is attempted, the presence of hypercellularity (>400,000 cells/ml), neutrophils >50% in the bronchoalveolar lavage fluid allows the diagnosis of VAP. IDSA/ATS guidelines suggest discontinuing antibiotics if final bronchoalveolar lavage culture results demonstrate <104 colony-forming units/ml, although it should be noted that bronchoscopic culture yields decline dramatically after 72 hours of antibiotic exposure.
Negative bronchoscopic cultures obtained from a patient on empiric antibiotic therapy can rule out multidrug-resistant organisms but do not completely exclude pneumonia. To detect the pathogens responsible for HAP and VAP, the polymerase chain reaction (PCR) test is increasingly used, which also guides the antibiotic regimen.
Nasal swab PCR to detect S : aureus demonstrated a high negative predictive value for methicillin-resistant S. aureus (MRSA) colonization in a patient population with a 10% prevalence of MRSA. The sensitivity of this test is higher when used for HAP (sensitivity 85%, specificity 92%) than for VAP (sensitivity 40%, specificity 94%).
Since a patient’s nasal colonization pattern reliably predicts which Staphylococcus species might be responsible for ongoing pneumonia, the nasal swab has been widely used as an antibiotic stewardship tool, resulting in the discontinuation of anti-MRSA agents when the result was negative, particularly in the context of HAP.
The respiratory viral panel , based on nasopharyngeal swab PCR, should be used especially during influenza season, to identify the viral causes of HAP and VAP, for which antibiotic therapy may not be necessary. Within the first 2 days in the hospital, it is likely that the organisms responsible for pneumonia have been acquired in the community. After 48 hours, the causative organisms are the pathogens the patient was exposed to in the hospital.
Antibiotic use within 90 days prior to new pneumonia is the only known risk factor consistently correlated with HAP and VAP from MRSA, and multidrug-resistant Pseudomonas aeruginosa . On the other hand, patients with the following risk factors may be predisposed to VAP, due to multidrug-resistant organisms:
• Cystic fibrosis or bronchiectasis
• Septic shock
• Acute respiratory distress syndrome
• Renal replacement therapy before AVN
• At least 5 days of hospitalization.
Viruses cause up to 20% of cases of HAP and VAP.
An observational study of 262 patients with HAP determined that respiratory syncytial virus, parainfluenza, and rhinovirus were the most common causative pathogens, while 8% of all HAP cases were caused by bacterial and viral coinfection. }
| Procalcitonin tests |
This test may help differentiate viral from bacterial pathogens in patients with HAP and VAP and potentially identify cases of co-infection. While any infectious pneumonia can elevate this serum biomarker, typical bacteria tend to have a higher procalcitonin level than atypical bacteria or viruses.
Cytokines, associated with bacterial infections, facilitate the release of procalcitonin, while interferons, associated with viral infections, inhibit its release. However, the procalcitonin test is not perfect, since it is not elevated in 23% of typical bacterial infections.
A systematic review and meta-analysis of 15 randomized controlled trials in ICU patients evaluated procalcitonin guidance for antibiotic initiation compared with clinical judgment alone and found no difference in short-term mortality. However, cessation of antibiotics based on procalcitonin was associated with a lower mortality rate than cessation of antibiotics based on clinical judgment alone.
In accordance with these results, the IDSA/ATS guidelines establish that procalcitonin should not replace clinical judgment to decide on the initiation of antibiotics in patients diagnosed with HAP or VAP, but allows monitoring the course of therapy to note the trend, and can be used in conjunction with clinical judgment to taper and eventually discontinue antibiotics.
Knowledge of the use of procalcitonin in the management of NAG and VAP is still in its infancy. There is no consensus on this topic, but the authors offer the following, based on their own experience and the relationship between procalcitonin levels and cytokines and interferons:
• An elevated procalcitonin level in patients with a PCR-proven viral infection, such as influenza, may suggest bacterial superinfection and warrants continuation of antibiotic therapy.
• A low positive or negative procalcitonin level in a patient with a viral infection proven by PCR provides greater confidence in making the diagnosis of HAP or viral VAP, and safely discontinuing antibiotics.
• A negative procalcitonin in a patient with a medical history suggesting an alternative cause of respiratory deterioration or marked improvement with diuresis may also aid cessation of antibiotics.
| Management of NAH and VAP |
Although in sepsis, delay in starting antibiotic therapy is associated with a higher risk of death, recent studies maintain that it is possible that not all patients with suspected VAP require immediate initiation of antibiotics.
2 different strategies can be used, clinical and bacteriological.
In the first, antibiotics are started in patients who present a new pulmonary infiltrate, which can be correlated with HAP or VAP as long as 2 of the following 3 criteria are met: fever, productive cough, and leukocytosis.
In the bacteriological strategy, antibiotics are continued until quantitative cultures of lower respiratory tract samples confirm the diagnosis of HAP or VAP. A single-center observational study compared these 2 strategies and found that patients treated with the clinical strategy were rapidly initiated on antibiotics and were less likely to receive appropriate initial treatment, longer duration of treatment, and had a significantly higher rate of in-hospital mortality. , possibly due to the selection of resistant organisms.
However, certain patients deserve prompt and aggressive antibiotic therapy, even before culture results are available: those with hemodynamic or respiratory instability; immunocompromised and, those whose timely sampling of lower respiratory tract secretions is not feasible.
| Initial empirical coverage of MRSA, Gram-negative bacteria |
Once the decision is made to treat a patient with suspected HAP or VAP, an institution-specific antibiogram is performed to guide selection of the empiric antibiotic regimen that best addresses the prevalence of local organisms and patterns of antibiotic resistance. If such an antibiogram is not readily available, a regimen with empirical coverage of methicillin-susceptible S. aureus and gram-negative bacilli, such as P. aeruginosa , will be indicated. e.g., piperacillin, zobactam, cefepime, levofloxacin, imipenem or meropenem.
> One antipseudomonal agent or two?
Patients who have recently received intravenous antibiotics or are at high risk of death warrant double coverage for P. aeruginosa with 2 different classes of antibiotics for empirical treatment of HAP.
In a patient diagnosed with VAP who is decided to be admitted to the ICU, where >10% of the gram-negative strains are resistant to an agent chosen to be administered as monotherapy, they should be treated with 2 additional antipseudomonal agents.
Patients with P. aeruginosa pneumonia complicated by bacteremia, who receive empiric combination antipseudomonal therapy, have a lower mortality rate than those who receive antipseudomonal monotherapy. Combination therapy ensures timely initiation of at least 1 active agent. Patients receiving antipseudomonal monotherapy may experience delays in initiating an appropriate antipseudomonal agent if the chosen agent demonstrates resistance.
> Is MRSA coverage necessary?
Not all patients with HAP or VAP need empiric MRSA coverage.
Vancomycin or linezolid should be administered , initiated only in those who received intravenous antibiotics in the last 90 days, are hospitalized in a unit where at least 20% of MRSA isolates, or, if the prevalence of MRSA is unknown or there is a high risk of mortality.
Furthermore, despite the role of aspiration in the development of NAH and VAP, empirical anaerobic coverage is not always indicated. This is because during the first 48 hours of hospitalization, bacterial colonization of the oropharynx and endotracheal tube evolves from the predominance of streptococci and anaerobic species to the predominance of gram-negative and nosocomial flora.
> Role of inhaled antibiotics. The guidelines discourage the use of intravenous aminoglycosides and polymyxins, given concerns about nephrotoxicity in critically ill patients with HNAH or VAP. However, for VAP due to pathogens sensitive only to aminoglycosides or polymyxins, their inhaled formulation can be used along with their intravenous formulations.
Systemic aminoglycosides reach low concentrations in respiratory secretions and the epithelial lining fluid of the lung, resulting in subtherapeutic levels that can stimulate the development of multidrug-resistant organisms.
Inhaled antibiotics are not associated with the degree of nephrotoxicity observed in patients receiving the intravenous equivalent of the formulations, and their addition to systemic antibiotics may allow higher drug concentrations at the site of infection, which in turn may help improve clinical cure rates and reduce the duration of MV.
Adjunctive inhaled antibiotics have not been shown to modify overall mortality in patients with VAP. The relationships between adjuvant inhaled antibiotics and length of ICU and hospital stay, and the prevalence of multidrug-resistant organisms have not yet been clarified.
| Personalized final regime |
Regardless of the empiric regimen initiated, culture sensitivities may allow antibiotic therapy to be tailored to the culprit organisms. responsible for the NAH and the NAV. The aspiration events that precipitate these pneumonic conditions are inherently polymicrobial. Thus, even if sputum cultures demonstrate only 1 pathogen, the final antibiotic regimen used to treat a patient with suspected aspiration should still include coverage of the oral and enteric flora, including gram-negative and anaerobic bacteria.
| Treatment duration |
The duration of the antibiotic course in patients with uncomplicated HAP and VAP is 7 days , since more days have not been shown to reduce the rates of recurrent pneumonia, therapeutic failure, duration of mechanical ventilation, hospital stay or mortality.
If a patient is hemodynamically stable, requires less oxygen, and is tolerating oral intake, the course of oral antibiotics can be completed. HAP and VAP associated with pulmonary or extrapulmonary complications (empyema, bacteremia) deserve a longer course of specific treatment.
Pneumonias due to Pseudomonas or Acinetobacter species are also considered complicated and require a minimum of 2 weeks of antibiotic therapy, due to the risk of relapse associated with a shorter therapeutic course.
Follow-up chest imaging during the same admission is not indicated unless the patient continues to worsen, in which case a repeat chest x-ray or CT scan will be performed, which could detect a pulmonary complication requiring procedural intervention or, alternatively, , can guide the doctor to look for other causes not related to the worsening, if there is improvement in the radiological signs, which also leads to consultation with Infectious Diseases and Pneumology.
| Prevention of HAP and VAP |
Prevention is as important as diagnosis and treatment, and depends on multiple approaches, in order to address risk factors for aspiration and nosocomial transmission of diseases.
> Prevention of colonization and aspiration . It is very important to prevent oropharyngeal colonization of pathogenic organisms, aspiration and consequent HAP or VAP: regular oral care, evaluation of the need for a proton pump inhibitor and histamine-2e receptor blockers, early identification and treatment of dysphagia, especially in the elderly and patients with recent stroke or recent surgical procedures:
A systematic review and meta-analysis that included 2 studies analyzing critically ill patients without MV reported that the risk of HAP can be reduced by oral cleaning with lcorhexiidine, electric toothbrushing, and oral hygiene instruction. There is significant evidence supporting oral care in the prevention of VAP.
Several institutions around the world have reported lower incidence of VAP related to URI “packages ,” which include an oral care component. One institution implemented a protocol that involves oral cleansing with chlorhexidine, twice daily, in addition to elevating the head of the bed to >30º, weaning attempts once/day, prompted by respiratory therapy, and placement of a catheter orogastric, for all ventilated trauma patients.
One year after implementation of this protocol, the incidence of VAP decreased and patients without VAP accumulated fewer total ventilator days, ICU days, and hospitalization days, although their mortality rate was no lower than in patients with VAP.
Other strategies to reduce the risk of aspiration include maintaining tracheal cuff pressure, eliminating nonessential tracheal suction, and avoiding gastric overdistension.
A 20-bed academic medical ICU center developed a work group and educational session to raise awareness of aspiration prevention with subsequent assessments of compliance with these strategies. These interventions increased compliance dramatically over a 2-year period, during which the center noted a 51% decrease in VAP incidence and decreased ventilator use.
