Category Archives: SYNDROMES

Everything You Need To Know About the New ATS/IDSA Community-Acquired Pneumonia Guidelines

The ATS and IDSA recently released the much-anticipated update to the community-acquired pneumonia (CAP) guidelines. The previous version was published back in 2007 and the new guidelines have included some major changes. Here is a rundown of all those changes that you need to know. 

1. Health care associated pneumonia (HCAP) no longer exists

HCAP was an entity created with the 2007 CAP guidelines. It encompassed non-hospital acquired pneumonia in patients who had recent contact with the healthcare system. The recommendation was to treat HCAP with empiric broad-spectrum antibiotic therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PsA). With this strategy however, we were over-treating a lot of people. This study found that while 30% of all patients hospitalized for CAP received empiric anti-MRSA treatment, only 0.7% of all patients had MRSA pneumonia.

In the new guidelines, HCAP no longer exists. Instead, the guidelines emphasize assessment of risk factors for pathogens such as MRSA and PsA.

2. Treatment is now based on severity of the pneumonia rather than the location of the admitted patient

Prior guidelines differentiated antibiotic recommendations based on patient triage to the floor or the intensive care unit. In the new guidelines, treatment recommendations are based on the severity of the pneumonia, based on a list of criteria:

3. Only obtain blood cultures in severe CAP or if risk factors for MRSA and/or PsA are present

The new guidelines focus on cost-effective use of diagnostic tests.
Outpatient setting: recommend against any diagnostic testing (except for a chest X-ray)
Inpatient non-severe pneumonia: recommend blood cultures and sputum gram stain/culture ONLY if risk factors for MRSA and/or PsA are present
Inpatient severe pneumonia: recommend blood cultures, sputum gram stain/culture, Streptococcus pneumoniae urine antigen, and Legionella urine antigen and PCR/culture
*Legionella diagnostic tests are also recommended in times of an outbreak 

These recommendations are based on literature demonstrating that:

  • Overall prevalence of true positive blood cultures is 1-9% in patients with CAP3-6
  • The majority of true positive blood cultures occur in patients with severe CAP6,7
  • Blood culture results change clinical management in <2% of patients with CAP3,4,6
  • The rate of blood culture contaminants is similar to the rate of true blood culture positives, resulting in unnecessary antibiotics and extended lengths of stay in the hospital3,4,6

4. Procalcitonin should NOT be used in the diagnosis of CAP

Procalcitonin is not a reliable marker for diagnosis of bacterial infections; it has roughly 65-75% sensitivity for detecting bacterial pneumonia8. Consequently, the risk of not treating bacterial CAP due to a low procalcitonin level can lead to poor outcomes. Although there is data to support use of procalcitonin in determining the duration of antibiotics in CAP9,10, the guidelines recommend use only in situations where duration exceeds the recommended 5-7 days.

5. The guidelines recommend use of the Pneumonia Severity Index (PSI) over the CURB-65 for determining need for admission

The argument from the guideline authors is that there is more literature in support for PSI in accurately predicting mortality rather than the CURB-65 score11-14. However, PSI incorporates data that may not be available in all circumstances, and certainly will not be available to the outpatient clinician who is trying to decide whether to admit a patient or not (such as pH, which can only be obtained from an arterial blood gas). So, although PSI may be recommended for use in the emergency department, the CURB-65 will likely remain in use, especially due to its efficiency in the outpatient setting.

6. Algorithm for CAP antibiotic treatment
The meat of the guidelines is the treatment regimens – and there are quite a few changes.

  • 1) Macrolides are no longer recommended as first line therapy in uncomplicated outpatient CAP unless the local streptococcal resistance to azithromycin is <25% (this study shows that most parts of the U.S. have resistance rates >25%).
  • 2) Amoxicillin and doxycycline take the place of macrolides as first line treatment in uncomplicated outpatient CAP.

You may be thinking – “wait, amoxicillin doesn’t even cover atypical pathogens (i.e.  Mycoplasma pneumoniae and Legionella pneumophila)!” This is true. But studies have shown that in otherwise-healthy patients, there was no difference in outcomes among those who received amoxicillin vs. an antibiotic that treats atypical organisms16. Exactly why that is remains unclear, but could be because healthy individuals clear the infection on their own or because the majority of these pneumonias are actually due to a virus, so they would improve with or without any antibiotics 5.

  • 3) In hospitalized patients:
    • Non-severe CAP – only treat empirically for MRSA and/or PsA if the organism has been isolated from the patient’s respiratory tract in the past
    • Severe CAP – treat empirically for MRSA and/or PsA if the patient has any risk factors for MRSA and/or PsA respiratory infection

7. Treat anaerobes only in cases with suspected or proven lung abscess and/or empyema

Empiric treatment of anaerobes in aspiration pneumonia remains controversial, but the new guidelines recommend only treating anaerobes if there is suspicion for or a proven lung abscess and/or empyema.

8. Continue antibiotics for at least 48 hours in patients who are diagnosed with influenza pneumonia

This recommendation is based off the data that influenza infection predisposes to subsequent bacterial superinfections17 and a patient could have both a viral and a bacterial pneumonia at the same time. The guidelines state that if there is significant clinical improvement in 48 hours and no evidence to suggest a superimposed bacterial pneumonia, antibiotics can be discontinued at that time.

9. Duration of antibiotics is based on clinical improvement (but should be a minimum of 5 days)

Gone are the days of prespecified number of days for antibiotic duration. Instead, monitor the patient for signs of clinical improvement.

  • If cultures are not growing MRSA and/or PsA, can stop empiric treatment for MRSA and/or PsA.
  • If clinically improving, stop antibiotics following 48 hours of clinical improvement after a minimum of 5 days. Clinical improvement is determined by resolution of vital sign abnormalities, ability to eat/improved appetite, and normal mentation.

10. Do not use corticosteroids as adjunctive treatment and do not obtain routine follow up chest X-rays

These were not necessarily strategies that I employed prior to the publication of these guidelines, and corticosteroid use in CAP is controversial, but at this time, there is no strong data to support either of these adjunctive management strategies in patients with CAP.

References:

1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Resp Crit Care Med. 2019; 200(7):e45-e67.
2. Self WH, Wunderink RG, Williams DJ, et al. Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes. Clin Infect Dis. 2016; 63(3):300-309.
3. Chalasani NP, Valdecanas MA, Gopal AK, McGowan JE Jr, and Jurado RL. Clinical utility of blood cultures in adult patients with community-acquired pneumonia without defined underlying risks. Chest. 1995; 108(4):932-936.
4. Corbo J, Friedman B, Bijur P, and Gallagher EJ. Limited usefulness of initial blood cultures in community acquired pneumonia. Emerg Med J. 2004; 21(4):446-448.
5. Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. New Eng J Med. 2015. 373:415-427.
6. Lee JH and Kim YH. Predictive factors of true bacteremia and the clinical utility of blood cultures as a prognostic tool in patients with community-onset pneumonia. Medicine (Baltimore). 2016; 95(41):e5058.
7. Waterer GW and Wunderink RG. The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures. Respir Med. 2001; 95(1):78-82.
8. Self WH, Balk RA, Grijalva CG, et al. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis. 2017;65(2):183-190.
9. Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017; 10:CD007498.
10. Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018;18(1):95-107.
11. Aujesky D, Auble TE, Yealy DM, et al. Prospective comparison of three validated prediction rules for prognosis in community-acquired pneumonia. Am J Med. 2005; 118(4):384-392.
12. Marrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, and Feagan BG. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL  Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin. JAMA. 2000; 283(6):749-755.
13. Carratala J, Fernandez-Sabe N, Ortega L, et al. Outpatient care compared with hospitalization for community-acquired pneumonia: a randomized trial in low-risk patients. Ann Intern Med. 2005;142(3):165-172.
14. Renaud B, Coma E, Labarere J, et al. Routine use of the Pneumonia Severity Index for guiding the site-of-treatment decision of patients with pneumonia in the emergency department: a multicenter, prospective, observational, controlled cohort study. Clin Infect Dis. 2007;441(1):41-49.
15. Blondeau JM and Theriault N. Application of the Formula for Rational Antimicrobial Therapy (FRAT) to Community-Acquired Pneumonia. J Infect Dis Ther. 2017;5:313.
16. Postma DW, van Werkhoven CH, van Elden LJR, et al. Antibiotic Treatment Strategies for Community-acquired Pneumonia in Adults. New Eng J Med. 2015;372:1312-1323.
17. Metersky ML, Masterton RG, Lode H, File TM Jr, and Babinchak T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis. 2012;16(5):e321-331.

Latent vs. Active TB

Tuberculosis is the leading cause of death globally from an infectious agent. In 2017, an estimated 10 million people developed TB disease and an estimated 1.6 million died1. A recent study demonstrated that <57% of internal medicine housestaff across 7 academic institutions in the U.S. correctly answered 9 out of 10 questions assessing knowledge of assessment and diagnosis of tuberculosis2. This post addresses these questions and to helps clarify latent vs. active TB in a clinical setting.

The primary focus for this blog post is pulmonary TB. Be aware that although the most common presentation of TB is with pulmonary symptoms, TB can present anywhere in the body and sometimes can present without pulmonary symptoms.

But first, definitions.

Definitions

Latent infection – the bacteria lies dormant in the body and does not cause any symptoms, typically tests for latent infection (see later section) will be positive

Active disease – the individual is experiencing symptoms due to the infection in the body, typically with characteristic imaging findings and microbiological confirmation

Primary disease – immediate onset of active disease after infection

Reactivation disease – onset of active disease after a period of latent infection

Extra-pulmonary disease – presence of bacteria outside of the lungs (the primary organ of infection)

Disseminated disease – two or more noncontiguous sites resulting from lymphohematogenous dissemination

Miliary disease – lesions in the lung that resemble millet seeds; seen in some cases of disseminated TB

Step 1: Risk stratification

Risk factors for TB exposure

  • having close contact with individuals who have active tuberculosis (roommates, family, friends, caregivers)
  • living/had lived in a country that is endemic for TB
  • living/working in a prison
  • living/working in a homeless shelter
  • injecting drugs
  • living/working in any other facility/institution that has high rate of TB (hospitals, nursing homes, residential homes for HIV patients) 

*USPSTF gives a grade B recommendation for screening those at increased risk (see list above) for latent tuberculosis infection4

Risk factors for TB reactivation

A. Normal host

  • 5-10% of reactivating TB in a lifetime6,13
  • 50% of that 5-10% is within the first 2-5 years of infection6,13

B. Age – immunity weakens in the elderly

C. Immunosuppression

  • HIV
  • End stage renal disease
  • Diabetes mellitus
  • Lymphoma
  • Corticosteroid or TNF-alpha inhibitor use
  • Cigarette smoking

Step 2: Why is it important to distinguish latent TB from active TB?

The two syndromes are treated completely differently. Latent TB is non-infectious and does not require treatment to prevent progression of disease or transmission to others, but instead to prevent future reactivation. Active TB is infectious and needs to be treated to prevent spread of TB to others. The medications, doses and duration of therapy to treat these syndromes are also different from each other.

Active TB

A. Clinical symptoms

  • fevers/chills, night sweats, weight loss, SOB and/or cough
  • depending on site of TB disease, can have extrapulmonary symptoms (GI, CNS, spine, etc)
  • subacute to chronic onset of symptoms (typically > several weeks)

B. Imaging

  • will typically have active pulmonary abnormalities seen on imaging (this can be any type of abnormality – infiltrates, cavitary lesions, effusions, or solitary nodules)
  • although the most common cause of apical lung scarring is prior TB infection, lung abnormalities DO NOT have to be in the apices of the lungs (they can be anywhere)

Latent TB
(make diagnosis ONLY after you have excluded active TB)

A. Clinical symptoms

  • the patient is asymptomatic (= NO symptoms of active TB)

B. Imaging

  • there is no active lung abnormality on chest imaging
  • (calcified granulomas/nodules or anything that is deemed old, healed scarring is excluded)

*If there are any signs suggestive of active TB, then the patient should undergo active TB evaluation (discussed below). If there is no evidence of active TB, then treatment can be based on latent TB diagnostics (discussed below).

Step 3: Evaluating for TB – diagnostic tests

A. Active TB tests (pulmonary TB)

  • obtain 2-3 sputum samples, ideally at least 8 hours apart, may require sputum induction if patient is not able to cough up sputum.
  • one ideally should be in the morning (highest burden of TB in the morning due to pooling of secretions overnight)
  • obtaining a bronchoscopy sample only counts for one sample
  • send a nucleic acid amplification test (NAAT) on the 1st sputum sample

1. AFB smear – fluorochrome stain of the clinical specimen

  • sensitivity = 67.5% (95% CI, 60.6 to 73.9)8
  • specificity = 97.5% (95% CI, 97.0 to 97.9)8

2. AFB culture – the gold standard test for tuberculosis diagnosis

  • can take up to 6 weeks to grow for solid culture versus ~ 2 weeks for liquid culture

3. PCR = NAAT (nucleic acid amplification test) – this is a DNA test using amplification methods

  • GeneXpert MTB/RIF assay is a brand test that combines the NAAT with rapid test for rifampin resistance sensitivity and specificity are high in pulmonary tuberculosis but is lower when used on specimens other than sputum.
    • sensitivity: 98% (for smear-positive, culture-positive specimens in HIV-negative patients)9
    • specificity: 99%9
  • this test can be run on both AFB smear negative and positive specimens (although sensitivity is lower on AFB smear negative specimens)
  • more specific than the smear because it tests directly for tuberculosis genes, whereas positive AFB smears can be due to non-tuberculous mycobacteria or other acid-fast staining bacteria (i.e. Nocardia)
  • positive result → TB diagnosis
    negative result → does not rule out TB

B. Latent TB tests

1. Tuberculin Skin Test (TST) = Purified Protein Derivative (PPD)

  • intradermal injection of tuberculin material (many different materials available)
  • causes a delayed-type hypersensitivity response in individuals whose immune system has been exposed to TB before
  • positive test = induration at the injection site within 48-72 hours
  • negative test = no induration

Threshold for treatment

TB, tuberculosis; CXR, chest X-ray; HIV, human immunodeficiency virus; IBW, ideal body weight

*individuals who have received the BCG vaccine in the past may also test positive with this test since their immune systems have been exposed to TB via the vaccine (although immunity tends to wane within 10 years if vaccine is administered in infancy)

2. Interferon Gamma Release Assay (IGRA) = QuantiFERON-TB Gold or Plus  OR T-SPOT.TB

  • blood test for detection of cell-mediated immune response to TB antigen
  • not affected by BCG vaccine or BCG treatment
  • 80-90% sensitivity, >95% specificity (sensitivity is diminished in immunocompromised hosts)5
  • the QuantiFERON-TB Gold test is made up of 3 tubes:
    • negative control (everyone should not react)
    • positive control (everyone should react), and the
    • TB antigen that is recognized by CD4 cells
  • **QuantGold-PLUS (a new test) has added a 4th tube with TB antigen that binds to CD8 cells thereby increasing sensitivity of the test12
  • positive test → patient’s blood reacted to the TB antigen and positive control but not the negative control
  • negative test → patient’s blood did not react to the TB antigen but did react to the positive control
  • indeterminate test → patient’s blood did not react to the positive control so test is invalid (this typically happens when the patient is immunocompromised and cannot mount an immune response to the positive control and thus would not react to the TB antigen either – even if they were exposed to TB)

*Indeterminate result DOES NOT mean it is in the middle between negative and positive. It means the test cannot provide a valid result.

*all latent diagnostic tests can cross-react in individuals infected with non-tuberculous mycobacteria (TST more so than the IGRA)

*Neither test is 100% sensitive and specific – if the patient has high pre-test probability for TB exposure and for future TB reactivation, ID physicians will sometimes treat for latent TB despite the negative tests 

Step 4: Treating TB

Treatment is complex and both choice of medication and duration depends on a variety of clinical and microbiological factors. Here is a basic overview of the difference in treatment between latent and active TB.

A. Latent TB (CDC)

*This is a useful calculator to determine the risks and benefits of TB reactivation vs. side effects from treatment in an individual patient. 

            a) Isoniazid – daily for 6 to 9 months

            b) Rifampin – daily for 4 months

            c) Rifapentine and isoniazid – weekly for 3 months

B. Active TB
— depends on susceptibility of bacteria and clinical syndrome
— RIPE therapy is the standard first-line therapy for fully-susceptible pulmonary TB infection with 2 months of all four drugs followed by 4 months of rifampin and isoniazid.

  R = rifampin

  I = isoniazid

  P = pyrazinamide

  E = ethambutol

*Ethambutol can be discontinued if drug susceptibility testing confirms a fully susceptible strain

*Patients with extensive disease e.g. cavitation or who remain smear and/or culture positive at 2 months may require a longer duration of therapy.

Don’t forget to:

  • give daily Vitamin B6 with isoniazid to prevent peripheral neuropathy
  • get baseline eye exam when starting ethambutol to enable monitoring for optic neuritis, particularly in patients with abnormal renal function
  • evaluate for other co-morbidities such as HIV, hepatitis B or C, diabetes or substance use

References:

1. Global Tuberculosis Report 2018: Executive Summary. World Health Organization. Published Sept 2018. Accessed Mar 10, 201

2. Chida N, Brown C, Mathad J, et al. Internal Medicine Residents’ Knowlesge and Practice of Pulmonary Tuberculosis Diagnosis. OFID. 2018; 5(7).

3. Tuberculosis (TB). Centers for Disease Control and Prevention. Available from: https://www.cdc.gov/tb. Accessed Feb 13, 2019.

4. US Preventive Services Task Force. Screening for Latent Tuberculosis Infection in Adults. US Preventive Services Task Force Recommendation Statement. JAMA. 2016; 316(9):962-969. doi:10.1001/jama.2016.11046

5. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Disease Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017; 64(2):111-115. doi: 10.1093/cid/ciw778

6. Horsburgh CR. Priorities for the Treatment of Latent Tuberculosis Infection in the United States. N Engl J Med. 2004; 350:2060-2067. DOI: 10.1056/NEJMsa031667

7. Pai M, Behr MA, Dowdy D, et al. Primer: Tuberculosis. Nature Reviews. 2016; 2:1-23.

8. Mathew P, Yen-Hong K, Vazirani B, Eng RHK, and Weinstein MP. Are Three Sputum Acid-Fast Bacillus Smears Necessary for Discontinuing Tuberculosis Isolation? J Clin Microbiol. 2002; 40(9):3482-3484. doi: 10.1128/JCM.40.9.3482-3484.2002

9. Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, and Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014 Jan 21;(1):CD009593. doi: 10.1002/14651858.CD009593.pub3.

10. Zeka AN, Tasbakan S, and Cavusoglu C. Evaluation of the GeneXpert MTB/RIF Assay for Rapid Diagnosis of Tuberculosis and Detection of Rifampin Resistance in Pulmonary and Extrapulmonary Specimens. 2011; 49(12):4138-4141. doi:10.1128/JCM.05434-11.  

11. Menzies D. Use of the tuberculin skin test for diagnosis of latent tuberculosis infection (tuberculosis screening) in adults. UpToDate. Available from: https://www.uptodate.com/contents/use-of-the-tuberculin-skin-test-for-diagnosis-of-latent-tuberculosis-infection-tuberculosis-screening-in-adults#H9. Accessed Feb 13, 2019.

12. QuantiFERON®-TB Gold Plus (QFT®-Plus) ELISA [Package Insert]. Hilden, Germany: Qiagen; 2016.

13. Comstock GW. Epidemiology of tuberculosis. Am Rev Respir Dis. 1982; 125(3 Pt 2):8.

Prevention of Clostridium difficile infection

Often, the focus of medical education is on clinical diagnosis and management of disease. But what about prevention? Prevention is key. Here are some ways for both the patient and healthcare provider to prevent further infections:

Prevent C.diff infographic

 

  1. Reduce transmission as much as possible
    1. Wash hands with soap and water after leaving the room of a patient with active C. difficile infection (CDI) OR use an alcohol-based hand sanitizer if a sink is not available
    2. Advocate healthcare facilities to:
      • place sinks nearby patient rooms
      • consider sink placement in the future construction of healthcare facilities
    3. Educate your patients and those who live with them to:
      • wash their hands well after using the toilet
      • have infected individuals use separate toilets and toilet accessories during treatment, if possible
  1. Avoid unnecessary antibiotic use
    • Avoid prescribing an antibiotic if low likelihood of bacterial infection
    • Narrow broad-spectrum antibiotics as soon as possible
    • Discontinue antibiotics as soon as possible
  2. Consider prophylactic PO vancomycin for patients with history of recurrent C. difficile infection
    • A retrospective review demonstrated that administration of PO vancomycin 125mg twice a day was associated with a lower incidence of recurrent C. difficile infection (4.2% vs. 26.6%, p<0.001)3 
  1. Educate yourself on the risks and benefits of probiotic use and be able to relay that information to your patients if they ask.
    • Some studies show no reduction in incidence of C. difficile infection with probiotic use6,7
    • Other studies (including a Cochrane review) show significant reduction in C. difficile infection incidence with probiotic use8,9,10,11
    • Studies have demonstrated that probiotics are more likely to reduce C. difficile infection incidence:
      • in patients with a baseline risk of C. difficile infection > 5%8,9
      • when probiotics are administered at higher doses10
      • when the probiotic consists of multiple strains10
      • when probiotics were administered within 2 days of antibiotic initiation11
    • This is the IDSA Clinical Practice Guidelines for C. difficile infection statement on probiotics:
      “There are insufficient data at this time to recommend administration of probiotics for primary prevention of CDI outside of clinical trials (no recommendation).”
      The guidelines cite the bias towards probiotics in many trials that enrolled mostly patients at very high risk of C.difficile infection and the potential for probiotics to cause harm by introducing new infections to hospitalized patients.

 Any prevention strategies I didn’t mention? What do you think is the most effective prevention strategy? I would love to hear your thoughts!

 

References

  1. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018; 66(7):1-48.
  2. Jorgensen JH, Pfaller MA, Carroll KC, et al. Manual of Clinical Microbiology, Eleventh Edition.
  3. Van Hise NW, Bryant AM, Hennessey EK, et al. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016; 63(5):651-653.
  4. Kelly CP, Lamont JT, and Bakken JS. Clostridium difficile infection in adults: Treatment and prevention. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-treatment-and-prevention]. Accessed May 25, 2018.
  5. Davidson LE and Hibberd PL. Clostridioides difficile and probiotics. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-and-probiotics]. Accessed Nov 13, 2018.
  6. Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013; 382(9900): 1249-57.
  7. Ehrhardt S, Guo N, Hinz R, Schoppen S, May J, Reiser M, et al. Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial. Open Forum Infect Dis. 2016; 3(1):ofw011.
  8. Goldenberg JZ, Yap C, Lytvyn L, Lo CK, Beardsley J, Mertz D, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017; 12:CD006095.
  9. Johnston BC, Lytvyn L, Lo CK, Allen SJ, Wang D, Szajewska H, et al. Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants. Infect Control Hosp Epidemiol. 2018; 39(7): 771-781.
  10. Johnston BC, Ma SSY, Goldenberg JZ, Thorlung K, Vandvik PO, Loeb M, et al. Probiotics for the Prevention of Clostridium difficile-Associated Diarrhea. Ann of Intern Med. 2012; 157:878-888
  11. Shen NT, Maw A, Tmanova LL, Pino A, Ancy K, Crawford CV, et al. Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficle Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology. 2017; 152(8): 1889-1900.

 

 

 

 

CAP vs. HCAP vs. HAP vs. VAP

This post is written by a guest writer, Jeff Pearson, PharmD. 

In 2016, the Infectious Diseases Society of America (IDSA) published updated guidelines for the treatment of hospital-acquired pneumonia (HAP) & ventilator-associated pneumonia (VAP).

The plan was to release new community-acquired pneumonia (CAP) guidelines shortly thereafter.

Those CAP guidelines have now been pushed back to be tentatively published in summer 2018.

This post is meant to cover some common misconceptions about the treatment of pneumonia and clinical pearls while we patiently await the release of the new guidelines.

Let’s start with the basics:

HCAP & CAP – those presenting to the hospital with pneumonia
HAP & VAP – those that developed pneumonia >48 hours after admission to the hospital or mechanical ventilation, respectively.

CAP vs HCAP vs HAP vs VAP

But I thought the term HCAP was gone…

While the 2016 guidelines no longer address HCAP, HCAP as an entity has not disappeared (despite what some may tell you). It will likely be discussed in the as-of-yet unreleased CAP guidelines. But in the meantime, feel free to use the algorithm presented above for guidance.

Previous guidelines from 2005 grouped HCAP in with HAP and VAP in terms of treatment. But since then, it’s been determined that not all HCAP patients require MRSA and Pseudomonas coverage. Many can be treated as typical CAP patients.

High-risk HCAP patients =

  • multiple risk factors for multi-drug resistant organisms (see green-box above)
  • require ICU admission to justify broad spectrum antibiotic treatment.

Treatment:

CAP/low risk HCAP
—–NO MRSA or Pseudomonas coverage
—–YES atypical pneumonia pathogens coverage (i.e. mycoplasma, legionella, chlamydia spp.)
Ex. Levofloxacin; ceftriaxone + azithromycin*

High-risk HCAP
—–YES MRSA and Pseudomonas coverage
—–YES atypical pneumonia pathogens coverage (i.e. mycoplasma, legionella, chlamydia spp.)
Ex. Vancomycin + cefepime + azithromycin*

HAP
—–YES MRSA and Pseudomonas coverage
—–Consider double pseudomonal coverage if patient is hemodynamically unstable
—–NO atypical pneumonia pathogen coverage
Ex. Vancomycin + cefepime*

VAP
—–YES MRSA and Pseudomonas coverage
—–Consider double pseudomonal coverage if patient is hemodynamically unstable
—–NO atypical pneumonia pathogen coverage
Ex. Vancomycin + cefepime + tobramycin*

*These are example regimens. Please reference your own institution’s pneumonia guidelines for additional information.

 

Duration of Treatment = 7 days!!!

* This can likely be even shorter in cases of CAP.
** From the IDSA: “There exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters.” 2

TAKE-HOME POINTS:

  • HCAP is still an entity – but it has been separated from HAP
  • CAP and HCAP – pneumonia <48 hours into a hospital stay
    HAP and VAP – pneumonia >48 hours into a hospital stay
  • CAP and low risk HCAPNO need for MRSA and Pseudomonas coverage
    High risk HCAP, HAP, and VAPDO need MRSA and Pseudomonas coverage
  • Duration of treatment = 7 days

 

References:

  1. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44:S27-S72
  2. 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
  3. Dinh A, Ropers J, Davido B, et al. Effectiveness of three days of beta-lactam antibiotics for hospitalized community-acquired pneumonia: a randomized non-inferiority double-blind trial [abstract]. ECCMID Madrid, Spain, April 22, 2018.

Guest author: Jeff Pearson is currently a PGY-2 infectious diseases pharmacy resident at Beth Israel Deaconess Medical Center in Boston, Massachusetts. He also serves as an adjunct faculty member at MCPHS University, lecturing and facilitating in various courses. He received his Doctor of Pharmacy from Northeastern University in 2014. His main area of interest is antimicrobial stewardship and he will be a senior pharmacist in infectious diseases at Brigham and Women’s Hospital after completing his residency year in August 2018.

 

Peer-reviewed by Milana Bogorodskaya, MD

Aspiration pneumonia vs. Aspiration pneumonitis

Why this matters:

Let me briefly tell you a story that was published in JAMA:  A patient was admitted to the hospital for seizures and intubated for airway protection. CXR showed infiltrates so patient was started on antibiotics and despite rapid improvement in 24 hours, received a 7 day course of antibiotics ‘just in case’. He was re-admitted to the hospital a week later with severe C.diff infection that did not improve despite adequate treatment and died in the hospital.

 

Antibiotics can cause harm. Sometimes they can be life-saving but risks and benefits need to be weighed each time.

 

Did that patient have aspiration pneumonia or aspiration pneumonitis?

 

Aspiration pneumonia = clinical evidence of pneumonia due to a bacterial infection

Aspiration pneumonitis = chemical lung injury due to gastric acid in the lower airways

– 13-26% can progress to develop bacterial pulmonary superinfections

 

Aspiration pneumonitis Aspiration pneumonia
Fever Low grade only/- +/-
Cough/SOB ++ ++
Hypoxia ++ ++
CXR infiltrate Resolves w/in 48-72 hrs Takes weeks to resolve
Sputum culture negative Positive/negative; purulent
Time to sx resolution Quick (48-72 hrs) Slow (>72 hrs)
Bronchoscopy Bronchial erythema Bronchial purulence

 

Risk factors for aspiration pneumonia:

  1. Risk of aspiration
  • altered mental status
  • esophageal disorders (inc. GERD)
  • neurological disorders that promote dysphagia (i.e. ALS, stroke, etc.)
  • seizures
  • vomiting
  • heavy alcohol use
  • recent intubation, bronchoscopy, upper endoscopy, or NG tube (any mechanical disruption of the natural mechanisms that prevent aspiration)
  1. Risk of aspirating increased inoculum of bacteria
  • poor dental hygiene
  • acid-suppressive medications (H2-blockers, PPIs) – loss of gastric acidity allows more pathogens to survive in the stomach ⇒ higher inoculum is present when aspiration occurs

Prevention of aspiration:

  • aspiration is pretty common in small amounts
  • it becomes pathogenic when a patient has chronic, recurrent aspiration or when the inoculum of bacteria in the aspirate increases to reach the threshold for causing chemical lung injury +/- bacterial infection.
  • there are not enough data to suggest that any interventions help to prevent recurrent aspiration

 

Microbiology:

  1. Flora – oral cavity and stomach (strep spp., H.flu, anaerobes, aerobic GNR)
  2. Community: strep spp., haemophilus influenza > anaerobes
  3. Hospital/long term care facilities:
    staphylococcus aureus, aerobic gram-neg bacilli >> anaerobes
    – these pathogens colonize the oral cavity
    Staph and aerobic GNR are more likely to be the infectious cause in these patients due to their intrinsic higher pathogenicity
  4. Anaerobespeptostreptococcus, fusobacterium nucleatum, Prevotella, Bacteroides spp.
  5. Most of these infections are polymicrobial

 

Diagnosis:

– usually a clinical diagnosis

sputum culture may help to isolate aerobic gram-neg bacilli or staph aureus to alter antimicrobial therapy

– “anaerobic bacteria are virtually never detected in pulmonary infections due to lack of access to specimens that are uncontaminated with the normal flora of the upper airways” (UpToDate) and we also do not culture sputum anaerobically so obligate anaerobes would not be able to grow in a typical sputum culture.

CXR should be ordered to assess for evidence of an infiltrate

  • Imaging: does location of infiltrate matter? YES.
    • aspiration in sitting position: lower lobes
    • aspiration in lying position: lower lobes OR posterior segment of upper lobes

 

Workup:

  • consider repeat CXR to evaluate for resolution of pulmonary infiltrate if patient has clinically improved within 48 hours ⇒ if CXR infiltrate resolved and symptoms resolved, likely pneumonitis and can discontinue the antibiotics.

So far, no trials looking at the utility of pro-calcitonin in differentiating aspiration pneumonitis vs. pneumonia that I know of, although would be a great study to do!

 

When to suspect anaerobic involvement
in pneumonia:

  • indolent course
  • risk factors for aspiration
  • absence of rigors
  • no main isolated pathogen on sputum cultures
  • putrid odor sputum
  • evidence of periodontal disease
  • imaging shows cavitation/necrosis or empyema

 

Treatment:

1. To treat or not to treat

  • It seems difficult to imagine coming into a patient’s room who is in respiratory distress with a leukocytosis and possible fever, and deciding to withhold antibiotics. At that time, everyone will likely start antibiotics.
  • Consider clinically re-evaluation at 48 hours – if CXR infiltrates and symptoms have resolved, it’s likely aspiration pneumonitis and you can probably stop antibiotics

2. Anaerobes: to treat or not to treat

  • community-acquired: always treat for anaerobes in addition to other common pathogens (see above)
  • hospital-acquired: consider treating if patient has poor dentition (that predisposes them to pathogenic anaerobic infections)

3. Antibiotic regimens (with anaerobic coverage)

  1. Community-acquired
    a) Amoxicillin-clavulanate or Ampicillin-sulbactam
    b) Ceftriaxone + metronidazole
    c) Clindamycin (if penicillin/cephalosporin allergic, not ideal regimen due to high resistance rates to certain pathogens)
    d) Moxifloxacin
  2. Hospital-acquired or recent history of antibiotics – cover for drug-resistant pathogens as well
    a) Vancomycin + Piperacillin-tazobactam
    b) Vancomycin + Carbapenem (if history of MDR pathogens)
  3. Duration – 7 days for uncomplicated pneumonia
    *For complicated pneumonia, duration of antibiotics will depend on the complication as well as patient’s clinical status and rate of recovery

 

Complications:

  1. ARDS (can happen both in pneumonitis and pneumonia)
  2. Lung abscess
  3. Empyema

 

Take-home points:

  • Aspiration pneumonitis ≠ Aspiration pneumonia
  • Re-evaluate patient in 48 hours and decide whether patient needs to continue antibiotics
  • Anaerobes are less likely to play a pathogenic role in hospital-acquired pneumonia (consider treatment for anaerobes if patient has poor dentition)

 

References:

1. Bartlett, J. G. 2017. Aspiration pneumonia in adults. Uptodate.
2. Finegold, S.M. 1991. Aspiration Pneumonia. CID. 13(9), S737-S742. DOI: 10.1093/clinids/13.Supplement_9.S737
3. Mandell, L. A. et al. 2007. IDSA guidelines for CAP. Section on aspiration pneumonia. 2007. CID. 44(S2): S27-72. DOI: 10.1086/511159
4. Dragan, V. et al. 2018. Prophylactic antimicrobial therapy for acute aspiration pneumonitis. CID. DOI: 10.1093/cid/ciy120
5. Loeb, M.B. et al. 2003. Interventions to prevent aspiration pneumonia in older adults: a systematic review. Journal of American Geriatric Society. 51(7):1018.
DOI: 10.1046/j.1365-2389.2003.51318.x
6.
Joundi, R.A. et al. 2015. Antibiotics “Just-In-Case” in a Patient with aspiration pneumonitis. JAMA Internal Medicine: Teachable moment – Less is more. 175(4); 489-490. DOI:10.1001/jamainternmed.2014.8030