UKHC Guideline for Management of Nosocomial Pneumonia in Adults
| Guideline/Protocol Title | UKHC Guideline for Management of Nosocomial Pneumonia in Adults |
|---|---|
| Authors | AST Committee |
| Committee Review | Antimicrobial Stewardship Subcommittee, ICU Committee Pharmacy and Therapeutics Committee |
| Target Population | Adult patients with or suspected nosocomial pneumonia |
| Overview | Provide evidence-based guidelines for the management of patients with nosocomial pneumonia |
| Effective Date | March 2017 |
| Revised Date | November 2021 |
| Expiration Date | November 2023 |
| Schedule for Periodic Review | Every 2 years or sooner if antibiogram data or newer published guidelines suggest changes needed. |
| Implementation Strategy | Education provided to pharmacists |
| Education Strategy | Guideline will be shared on CareWeb and the Pharmacy app |
| Primary Outcome(s) | Percent adherence to the guidelines |
| Outcome Assessment Plan | Assessed annually |
| Information Technology Needs | Access to CareWeb and Pharmacy App |
Guideline approved by the Antimicrobial Stewardship Team Subcommittee and Pharmacy and Therapeutics Committee. Prepared 3/28/2017. Updated 11/16/2021.
Guidelines for the Management of Nosocomial Pneumonia in Adults
Purpose of Guidelines
To provide evidence-based guidelines for the management of patients with nosocomial pneumonia at the UK Healthcare.
Background
The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) published updated guidelines for the management of hospital-acquired and ventilator-associated pneumonia (together referred to as nosocomial pneumonia) in 2016.1 This guideline update removed the concept of healthcare-associated pneumonia (HCAP), highlighted the importance of local susceptibility data in selecting empirical therapy, and emphasized short course therapy for all patients with nosocomial pneumonia. Given that nosocomial pneumonia accounts for up to 22% of all hospital-acquired infections (HAIs) and is associated with significant morbidity and mortality in hospitalized patients, this institutional guideline has been developed to adapt the IDSA/ATS 2016 recommendations to practice at University of Kentucky Healthcare.2
Definitions
Table 1: Definitions of various types of pneumonia1
| Term | Definition |
|---|---|
| Pneumonia | The presence of new lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin, which includes new onset fever, purulent sputum, leukocytosis, and decline in oxygenation |
| Hospital-acquired Pneumonia (HAP) | Pneumonia not incubating at the time of hospital admission and occurring 48 hours or more after admission |
| Ventilator-associated Pneumonia (VAP) | Pneumonia occurring greater than 48 hours after endotracheal intubation |
| Nosocomial Pneumonia | Pneumonia acquired after hospital admission, including hospital-acquired or ventilator-associated pneumonia |
| Ventilator-associated Tracheobronchitis (VAT) | Fever with no other recognizable cause, with new or increased sputum production, positive endotracheal aspirate culture (>106 cfu/mL) yielding a new bacteria, and no radiographic evidence of pneumonia |
Diagnosis and Initial Workup of Nosocomial Pneumonia
Nosocomial pneumonia should be suspected in patients admitted for ≥ 48 hours with new infiltrates on chest radiograph and infectious signs such as new onset fever, purulent sputum, leukocytosis, and decline in oxygenation.1 Initial workup of suspected nosocomial pneumonia should include the collection of respiratory and blood culture samples PRIOR TO the administration of antibiotics whenever possible.
Criteria for initiation of empirical therapy should include:
- Clinical criteria including radiographic evidence and infectious signs consistent with pneumonia
- Clinical scoring tools, such as the modified clinical pulmonary infection score (CPIS), are NOT recommended as an adjunct to clinical criteria in determining when to initiate therapy for nosocomial pneumonia
- Biomarkers, such as procalcitonin (PCT) and C-Reactive Protein (CRP), are NOT recommended as an adjunct to clinical criteria in determining when to initiate therapy for nosocomial pneumonia
- For more information on optimal use of PCT, please see https://antimicrobial.ukhc.org/wp-content/uploads/sites/170/2021/03/UKHC-Adult-Procalcitonin-Protocol.pdf
Microbiologic workup should include:
- Respiratory Cultures
- Preferred: non-invasive, semiquantitative culture methodologies including sputum and endotracheal aspirate
- Alternative: invasive, quantitative protected alveolar lavage (PAL) or bronchial alveolar lavage (BAL)
- If invasive cultures are obtained, consideration should be given to withholding antibiotic therapy in patients with quantitative culture results that are below the threshold considered likely to be clinically significant provided cultures are obtained prior to or soon after the initiation of antibiotic therapy.
- PAL/BAL <104 cfu/mL
- Avoidance of antibiotic therapy in this population has been associated with similar clinical outcomes, less antimicrobial use, and fewer superinfections. Consideration should be given to the potential alternative sources of infection, antimicrobial therapy prior to the time of culture, degree of clinical suspicion, signs of severe sepsis, and evidence of clinical improvement when deciding whether or not to withhold antibiotics.
- If invasive cultures are obtained, consideration should be given to withholding antibiotic therapy in patients with quantitative culture results that are below the threshold considered likely to be clinically significant provided cultures are obtained prior to or soon after the initiation of antibiotic therapy.
- Recommended: Legionella Testing
- Legionnaire’s disease can mimic signs and symptoms of pneumonia caused by other pathogens and rarely grows on normal culture medium. Per the Centers for Disease Control and Prevention (CDC) recommendations, all patients with healthcare-associated pneumonia (pneumonia with onset ≥48 hours after admission) should be tested for legionella.
- Preferred diagnostic tests are legionella PCR AND the legionella urinary antigen. If PCR or legionella antigen is positive, lower respiratory culture for legionella is recommended.
- Legionnaire’s disease can mimic signs and symptoms of pneumonia caused by other pathogens and rarely grows on normal culture medium. Per the Centers for Disease Control and Prevention (CDC) recommendations, all patients with healthcare-associated pneumonia (pneumonia with onset ≥48 hours after admission) should be tested for legionella.
- Blood Cultures
- At least one set of blood cultures including an aerobic and anaerobic bottle drawn from a peripheral stick should be obtained.
- Urine Testing
- Legionella urinary antigen is recommended along with legionella PCR as above for all cases of nosocomial pneumonia
- MRSA Nasal Screening
- MRSA PCR-based nares screening should be utilized in patients with HAP and VAP to assist in the de-escalation of MRSA targeted antibiotics (for example, linezolid or vancomycin).
- Background: MRSA is a common colonizer of the nares, thus screening has been shown to have a high negative predictive value for MRSA pneumonia. In a 2018 meta-analysis, the negative predictive value (NPV) for MRSA pneumonias was found to be 96.5%. Clinical outcomes, including mortality rates, have been noted to be similar among patients with therapy de-escalations derived from MRSA nasal screens. MRSA nares screens do not have predictive value in the diagnosis of MRSA pneumonia and should only be used as a marker for de-escalation. The evidence is strongest in patients with HAP, where the evidence in VAP remains less clear as MRSA can be introduced by an alternative route (artificial airway). Screening is still recommended in VAP as NPV has been reported to be 94.8%; however, it is important to take an individualized approach when considering de-escalating in this population (consider hemodynamic stability, history of MRSA infection etc.)
- Considerations
- PCR-based screening is preferred. Culture-based screens are performed in the ICUs on a weekly basis and may be used if available. MRSA screen results can be utilized if known within a week prior to pneumonia diagnosis.
- Screening should not be used for therapy decisions in patients with recent (within 30 days) nasal MRSA decolonization. At UK HealthCare, this occurs in pediatric and adult patients with a foley catheter, central line, or history of MRSA, as well as all ICU patients.
- Nasal screening may occur after initiation of therapy as parenteral antimicrobials are ineffective at clearing nasal colonization and MRSA persists in the respiratory tracts for the first few days of therapy.
- MRSA PCR-based nares screening should be utilized in patients with HAP and VAP to assist in the de-escalation of MRSA targeted antibiotics (for example, linezolid or vancomycin).
Risk Factors for Multidrug Resistance
Table 2: Risk factors for multidrug resistant (MDR) pathogens in nosocomial pneumonias1
| HAP | VAP | |
|---|---|---|
| Risk Factors for Any MDR Organism | - IV antibiotics within 90 days | - IV antibiotics within 90 days - ≥ 5 days of hospitalization prior to VAP - Septic shock - ARDS preceding VAP - RRT prior to VAP |
| Risk Factors for MDR Pseudomonas aeruginosa | - Prior use of IV antibiotics within 90 days - Bronchiectasis - Cystic Fibrosis |
|
| Risk Factors for MRSA | - Prior use of IV antibiotics within 90 days | |
Abbreviations: HAP, hospital-acquired pneumonia; VAP, ventilator-associated pneumonia; MDR, multidrug resistant; IV, intravenous; ARDS, acute respiratory distress syndrome; RRT, renal replacement therapy
Recommended Empirical Therapy for Nosocomial Pneumonia
- Treatment of ventilator-associated tracheobronchitis (VAT) is NOT recommended
- Dosing assumes normal renal function or high-flow continuous renal replacement. Consult a pharmacist to assist with dosing in renal impairment.
- Recommendations for empirical therapy and dosing reflect the resistance patterns outlined on the hospital antibiogram which can be accessed on CareWeb (http://www.hosp.uky.edu/Careweb/antibiograms.html)
Table 3: Recommended empirical therapy for the treatment of nosocomial pneumonia at UK Healthcare1
| SELECT ONE AGENT FROM EACH CLASS | |||
|---|---|---|---|
| Primary Therapy | Non-type I Penicillin Allergya | Type I Penicillin Allergya | |
| Antipseudomonal Beta-lactam | Cefepime 2g IV q8h EIb OR Piperacillin/tazobactam 4.5 g IV q6h EIb |
Cefepime 2g IV q8h EIb | Meropenem 2g IV q8h EIb OR Aztreonam 2g IV q8h EIb |
| Double Gram-negative Therapy | Tobramycin OR Amikacin (pharmacy to dose)d Activity of antipseudomonal beta-lactams against P. aeruginosa is ≤85% based on the hospital antibiogram; therefore, aminoglycoside combination therapy is needed to provide adequate empirical activity (>90%). At least a single dose of an aminoglycoside should be STRONGLY considered for patients with suspected nosocomial pneumonia. |
||
| Anti-MRSA Agent | Vancomycinc (pharmacy to dose)d | ||
Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; IV, intravenous; EI, extended-infusion; DBW, dosing body weight [IBW + 0.4(ABW-IBW)]; PO, orally; ABW, actual body weight
Doses listed are for patients with normal renal function
a Assessment of beta-lactam allergies should include the type of reaction, when it occurred, what treatment measures were taken, and any antibiotics tolerated since the reaction occurred. Cross-reactivity between penicillins and meropenem in patients with type 1 reactions (anaphylaxis, hives, and angioedema) is estimated at 0.5% based on recent studies. Due to poor activity against many nosocomial gram-negative organisms, aztreonam should be reserved for allergy histories compatible with severe type I reactions.
b Antipseudomonal beta-lactams should be administered as a one-time loading dose given over 30 minutes followed by an extended-infusion regimen with each dose infused over 3 hours
c If concerned for adverse effects related to vancomycin, can consider linezolid 600mg IV/PO as an alternative
d In patients with normal renal function, consider the following doses based the Clinical Pharmacokinetics Service and Anticoagulation Guidelines: Tobramycin 7 mg/kg DBW IV q24h, Amikacin 15-20 mg/kg DBW IV q24h, Vancomycin 25-30 mg/kg ABW x 1 dose, then maintenance dosing based on first-dose of kinetics or population parameters
Role of Inhaled Antibiotic Therapy
- The role of inhaled antibiotics in the treatment of ventilator-associated tracheobronchitis and nosocomial pneumonia has not been clearly defined. Clinical outcomes data are limited; however, no effect on mortality, ICU length of stay, or hospital length of stay has been clearly demonstrated. Additionally, inhaled therapy is associated with significant cost to the institution.
- It is strongly encouraged to obtain an ID consult for patients that receive inhaled antibiotics for nosocomial pneumonia.
Table 4: Indications for inhaled antibiotic therapy1
| Inhaled Aminoglycosides (Tobramycin, Amikacin) | Inhaled Polymyxins (Colistin, Polymyxin B) | |
|---|---|---|
| Routine Use in Ventilator-associated Tracheobronchitis? | Not recommended | Not recommended |
| Routine Use in Nosocomial Pneumonia? | Not recommended | Not recommended |
| Indication for Use | Nosocomial pneumonia, as an adjunct to systemic therapy when isolated organisms are susceptible only to aminoglycosides or polymyxins | |
Definitive and Pathogen-specific Therapy
- Antibiotic therapy should be tailored based on culture data rather than fixed. Empirical therapy should be de-escalated based on the results of microbiologic workup and the patient’s clinical status.
- De-escalation of vancomycin therapy should be strongly considered if MRSA is not isolated within 48-72 hours, or MRSA surveillance culture, PCR, or MDRT of nares is negative for MRSA. This is due to the significant risk of nephrotoxicity in a critically ill population using combination therapy including vancomycin and a beta-lactam
Table 5: Recommended antibiotics for selected pathogens
| Pathogens | Antibiotic Therapy Following Organism Identificationa | Antibiotic Therapy Following Susceptibility Results | Combination Therapy Following Susceptibility Resultsf |
|---|---|---|---|
| Pseudomonas aeruginosa | Piperacillin/tazobactam OR Cefepime OR Meropenem + Tobramycin OR Amikacina |
Antipseudomonal Beta-lactamb, ciprofloxacin or levofloxacin For MDR P. aeruginosa: Ceftolozane/tazobactamI +/- Amikacin (Consult ID) |
Yes, if unresolving septic shock or at a high risk of death (≥25%) |
| Acinetobacter baumannii | Meropenemc +/- Polymyxin Bd |
Susceptible Beta-lactam | No, unless the isolate is only susceptible to polymyxins. ID consult is strongly recommended. |
| AmpC-producing Enterobacteralese (Serratia marsescens, Citrobacter freundii, Enterobacter spp) |
Cefepime | Cefepime OR Levofloxacin | No |
| ESBL-producing Enterobacterales (CTX-M on genetic testing within the blood. Common pathogens which may harbor ESBL enzymes include E. coli, Klebsiella spp, and Proteus spp) |
Meropenem | Meropenem OR Levofloxacin | No |
| Carbapenemase-producing Organisms (CRO) (Recommendations are for isolates only susceptible to aminoglycosides and/or polymyxins) |
For KPC containing Enterobacterales: Meropenem/vaborbactamI,J +/- Amikacin (Consult ID) For IMP, NDM, or VIM containing Enterobacterales: Ceftazidime/avibactamI + Aztreonam (Consult ID) For OXA containing Enterobacterales: Ceftazidime/avibactamI (Consult ID) |
For KPC containing Enterobacterales: Meropenem/vaborbactamI,J +/- Amikacin (Consult ID) For IMP, NDM, or VIM containing Enterobacterales: Ceftazidime/avibactamI + Aztreonam (Consult ID) For OXA containing Enterobacterales: Ceftazidime/avibactamI (Consult ID) |
Yes |
| MRSA | Vancomycing | Vancomycin LinezolidK |
No |
| Legionella sp. | Azithromycinh | Azithromycin or Levofloxacin | No |
Abbreviations: ESBL, extended-spectrum beta-lactamase; MRSA, methicillin-resistant Staphylococcus aureus
a Recommendations based on anticipated susceptibility of isolated organism from the hospital antibiogram
b Antipseudomonal beta-lactams include aztreonam, cefepime, meropenem, or piperacillin/tazobactam
c Susceptibility to meropenem <70% according to hospital antibiogram. Strong consideration should be given to combination therapy in severe illness.
d Polymyxin B is preferred over colistin for the treatment of pulmonary source infections. Refer to the UK Healthcare Polymyxin Use Guidelines for information on dosing and administration (https://antimicrobial.ukhc.org/wp-content/uploads/sites/170/2021/03/Polymyxin-Guidelines-Draft.2021.pdf)
e Enterobacteriaceae considered to harbor the AmpC gene include Enterobacter spp, Serratia marsescens, and Citrobacter freundii.
f Combination definitive therapy after the acquisition of susceptibility results is necessary in cases where the risk for mortality is high or the isolate is only susceptible to adjunctive agents, such as aminoglycosides or polymyxins
g If concerned for adverse effects related to vancomycin, can consider linezolid 600mg IV/PO as an alternative
h Azithromycin or Levofloxacin are acceptable first line agents; however, azithromycin is preferred due to a narrower spectrum of activity
I Susceptibilities need to be released through the microbiology laboratory.
J Further options for KPC containing organisms: Ceftazidime/avibactam or Imipenem/cilastatin/relebactam,
K Due to good oral bioavailability, oral route is preferred when possible
Duration of Therapy
The standard duration of therapy for nosocomial pneumonia should be 7 days regardless of etiologic pathogen.1
- Patient-specific considerations
- The optimal duration of therapy for nosocomial pneumonia in immunocompromised patient populations has not been determined.
- The duration of therapy should be guided by improvement in clinical signs and symptoms as well as available microbiological data with a minimum duration of 7 days.
- Site-specific considerations
- Patients with bacteremia secondary to nosocomial pneumonia should in general be treated for at least 7-14 days depending on the pathogen. If organism is a gram-negative pathogen, then 7 days duration is warranted for the Enterobacterales and 10 days duration for non-lactose fermenting gram-negatives. More information can be found at https://antimicrobial.ukhc.org/wp-content/uploads/sites/170/2021/03/Updated-Duration-of-Treatment-Guideline-Aug-PT.pdf. If S. aureus is isolated, patients should be treated from the first negative culture. For duration and management, please refer to the “Staphylococcus aureus Bacteremia Treatment Guideline for Adults” at http://careweb/ICISdocs/SAB_Guideline.pdf.
- Pathogen-specific considerations
- Longer durations of therapy (i.e. 14-15 days) are no longer recommended for non-glucose fermenting gram-negative bacilli as no differences in mortality or recurrence were demonstrated in analysis by the 2016 guideline panel. Although there may be a small increase in risk of recurrence with these pathogens, it does not appear to affect clinical cure or mortality and is likely offset by a reduction in adverse effects, C. difficile colitis, and cost.
- Biomarker considerations
- Although procalcitonin is not recommended in determining when to initiate therapy for nosocomial pneumonia, trended procalcitonin levels may be used together with improvement in clinical signs of infection (leukocytosis, fever, oxygenation) as a guide for early de-escalation or discontinuation of therapy
- Given the recommendation for short course therapy for all episodes of nosocomial pneumonia and the cost of procalcitonin levels, procalcitonin monitoring is unlikely to provide significant benefit in decreasing duration of therapy and antibiotic days.
References
- 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(5):e61-e111.
- Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198-1208.
- Messonnier N, Breysse P. Developing a Water Management Program to Reduce Legionella Growth & Spread in Buildings. U.S. Department of Health and Human Services: Centers for Disease Control and Prevention. CS278126-A. 2017;1-36
- Parente DM, Cunha CB, Mylonakis E, et al. The clinic utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: a diagnostic meta-analysis with antimicrobial stewardship implications. Clin Infect Dis. 2018;67(1):1-7.
- Keene A, Vavagiakis P, Lee MH, et al. Staphylococcus aureus colonization and the risk of infection in critically Ill patients. Infect Control Hosp Epidemiol. 2005;26:622-628.
- Smith MN, Erdman MJ, Ferreria JA, et al. Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia. Journal of Critical Care. 2017;38:168–171.