Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

Anaerobes have been considered a major cause of aspiration pneumonia (AP) based on studies published in 1970’s (1-3). More recent data, however, suggest that anaerobes no longer play an important role in most cases of AP (4-7) and routine inclusion of specific anti-anaerobic drugs in their treatment is no longer necessary.

 
An important reason for anaerobes not playing an important role in AP in the current era is the change in the demographics of patients who may be affected. Patients reported in older studies often suffered from alcohol use disorder, drug ingestion, seizure disorders and acute cerebrovascular accident. In contrast, more recent data show that AP often occurs in nursing home residents, the elderly with cognitive impairment, and those with dysphagia, gastrointestinal dysmotility or tube feeding (8,9).

 
In addition, many cases of AP reported in older studies involved delay of 4 or more days before seeking medical attention and, not surprisingly, often presented with lung abscess, necrotizing pneumonia, empyema, or putrid sputum, features that are relatively rare in the current era.

 
Further supporting the diminishing role of anaerobes in AP, are recent microbiological studies of the respiratory tract in AP revealing the infrequent isolation of anaerobes and, even when isolated, often coexisting with aerobic bacteria. The latter observation is important because, due to the alteration in the redox potential (9,10), treatment of aerobic bacteria alone may lead to less oxygenation consumption and less favorable environment for survival of anaerobes in the respiratory tract.

 
We should also always consider the potential adverse effects of unnecessary antibiotics with anaerobic activity in our frequently debilitated patients, including gastrointestinal dysbiosis (associated with Clostridiodes difficile infections and overgrowth of antibiotic-resistant pathogens such as vancomycin-resistant enterococci (VRE), hypersensitivity reactions, drug interactions, and central nervous system toxicity (11,12).

 
Thus, the weight of the evidence does not justify routine anaerobic coverage of AP in today’s patients.

 

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References
1. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Am J Med. 1974;56(2):202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
2. Bartlett JG, Finegold SM. Anaerobic pleuropulmonary infections. Medicine (Baltimore). 1972;51(6):413-50. https://www.ncbi.nlm.nih.gov/pubmed/4564416
3. Bartlett JG, Gorbach SL. The triple threat of aspiration pneumonia. Chest. 1975;68(4):560-6. https://www.ncbi.nlm.nih.gov/pubmed/1175415
4. Finegold SM. Aspiration pneumonia. Rev Infect Dis. 1991;13 Suppl 9:S737-42. https://www.ncbi.nlm.nih.gov/pubmed/1925318
5. Bartlett JG. How important are anaerobic bacteria in aspiration pneumonia: when should they be treated and what is optimal therapy. Infect Dis Clin North Am. 2013;27(1):149-55. https://www.ncbi.nlm.nih.gov/pubmed/23398871
6. El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003;167(12):1650-4. https://www.ncbi.nlm.nih.gov/pubmed/12689848
7. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999;115(1):178-83. https://www.ncbi.nlm.nih.gov/pubmed/9925081
8. Bowerman TJ, Zhang J, Waite LM. Antibacterial treatment of aspiration pneumonia in older people: a systematic review. Clin Interv Aging. 2018;13:2201-13. https://www.ncbi.nlm.nih.gov/pubmed/30464429
9. Mandell LA, Niederman MS. Aspiration Pneumonia. N Engl J Med. 2019 Feb 14;380(7):651-663. doi: 10.1056/NEJMra1714562. https://www.ncbi.nlm.nih.gov/pubmed/30763196
10. Walden, W. C., & Hentges, D. J. (1975). Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria. Applied microbiology, 30(5), 781–785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC187272/
11. Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1(2):101-14. https://www.ncbi.nlm.nih.gov/pubmed/11871461
12. Bhalla A, Pultz NJ, Ray AJ, Hoyen CK, Eckstein EC, Donskey CJ. Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol. 2003;24(9):644-9. https://www.ncbi.nlm.nih.gov/pubmed/14510245

 

Contributed by Amar Vedamurthy, MD, MPH, Mass General Hospital, Boston, MA

Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci?

Although meropenem is a broad spectrum antibiotic that covers many gram-negative and gram-positive organisms as well as anaerobes, its activity against enterococci is generally poor and leaves much to be desired.

In a study of ampicillin-sensitive E. faecalis isolates from hospitalized patients, only 36% of isolates were considered susceptible (MIC≤4 mg/L); activity against E. faecium isolates was similarly poor.1 Several other studies have reported the suboptimal activity of meropenem against both E. faecalis and E. faecium, 2-4 with susceptibility rates as low as 8.6% depending on the MIC break point used.3

A popular textbook and a handbook on infectious diseases also do not recommend the use of meropenem for treatment of enterococcal infections. 5,6

Of interest, the package insert states that meropenem is indicated for complicated skin and soft tissue infections due to a variety of organisms, including E. faecalis (vancomycin-susceptible isolates only), but not for complicated intra-abdominal infections or meningitis due this organism.7

In our patient with intraabdominal infection,  we may consider piperacillin-tazobactam instead.  Piperacillin-tazobactam is a broad spectrum antibiotic with excellent coverage against anaerobes and ampicillin-susceptible E. faecalis.1,8  

 

References

  1. Endtz HP, van Dijk WC, Verbrugh HA, et al. Comparative in-vitro activity of meropenem against selected pathogens from hospitalized patients in the Netherlands. J Antimicrob Chemother 1997;39:149-56. https://www.ncbi.nlm.nih.gov/pubmed/9069534
  2. Pfaller MA, Jones RN. A review of the in vitro activity of meropenem and comparative antimicrobial agents tested against 30,254 aerobic and anaerobic pathogens isolated world wide. Diag Microbiol Infect Dis 1997;28:157-63. https://www.ncbi.nlm.nih.gov/pubmed/9327242
  3. Hallgren A, Abednazari H, Ekdahl C, et al. Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems. J Antimicrob Chemother 2001;48:53-62. https://www.ncbi.nlm.nih.gov/pubmed/11418512
  4. Hoban DJ, Jones RN, Yamane N, et al. In vitro activity of three carbapenem antibiotics comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide. Diag Microbiol Infect Dis 993;17:299-305.https://www.ncbi.nlm.nih.gov/pubmed/8112045
  5. Chambers HF. Carbapenem and monobactams. In Mandell GL et al. eds. Principles and practice of infectious diseases. 2010, pp 341-45.
  6. Cunha CB, Cunha BA. Antibiotic essentials. 2017, pp 689-91.
  7. Meropenem.http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7253?searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dmeropenem%26t%3Dname
  8. Perry CM, Markham A. Piperacillin/tazobactam. Drugs 1999;57:805-43. https://link.springer.com/article/10.2165%2F00003495-199957050-00017

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Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci?

Is my hospitalized patient with possible pneumonia at risk of Clostridium difficile-associated disease after only 1-3 days of empiric antibiotic therapy?

Yes! Even relatively brief duration of antibiotic therapy may increase the risk of Clostridium difficile-associated disease (CDAD) in a susceptible host.
In a study of hospitalized patients with new-onset diarrhea, prior exposure to levofloxacin and cefazolin was significantly associated with CDAD with the median duration of therapy for levofloxacin of 3 days (range 1-18 days), and for cefazolin 2 days (range 1-3 days) (1). Similarly, a study in hospitalized patients during a CDAD epidemic found a significantly increased risk of CDAD among patients who received fluoroquinolones for only 1-3 days (hazard ratio 2.4) with a 95% confidence interval (1.6-3.6) that overlapped 4-6 days and ≥ 7 days treatment groups (2). Yet another study found no significant difference in the risk of CDAD between those on antibiotic for < 4 days vs 4-7 days of antibiotics (3). CDAD following a single dose of cefazolin has also been reported (4).
Of interest, laboratory studies in mice have shown a profound alteration of intestinal microbiota following a single dose of clindamycin, resulting in increased susceptibility to C. difficile colitis (5).
So although duration of antibiotic therapy is an important factor in CDAD (3, 6) and we should minimize the duration of antibiotic therapy whenever possible, not starting antibiotics in the absence of clear indication is even better!

References
1. Manian FA, Aradhyula S, Greisnauer S, et al. Is it Clostridium difficile infection or something else? A case-control study of 352 hospitalized patients with new-onset diarrhea. S Med J 2007;100:782-786. https://www.ncbi.nlm.nih.gov/pubmed/17713303
2. Pepin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254-60. https://www.ncbi.nlm.nih.gov/pubmed/16206099
3. Stevens V, Dumyati G, Fine LS, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011;53:42-48. https://www.ncbi.nlm.nih.gov/pubmed/21653301
4. Mcneeley SG, Anderson GD, Sibai BM. Clostridium difficile colitis associated with single dose cefazolin prophylaxis. Ob Gynecol 1985;66:737-8. https://www.ncbi.nlm.nih.gov/pubmed/4058831
5. Buffie CG, Jarchum I, Equinda M, et al. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect Immun 2011;80: 62-73. https://www.ncbi.nlm.nih.gov/pubmed/22006564
6. Chalmers JD, Akram AR, Sinanayagam A, et al. Risk factors for Clostridium difficile infection in hospitalized patients with community-acquired pneumonia. J Infect 2016;73:45-53. https://www.ncbi.nlm.nih.gov/pubmed/27105657

Disclosure: The contributor of this post was a coinvestigator of a cited study (ref. 1).

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Is my hospitalized patient with possible pneumonia at risk of Clostridium difficile-associated disease after only 1-3 days of empiric antibiotic therapy?

My elderly patient on chronic warfarin with recent hospitalization for soft tissue infection is now readmitted with gastrointestinal bleed and a newly-discovered supra-therapeutic INR? Why did her INR jump?

Assuming no recent changes in the dose of warfarin, one potential culprit may be her recent antibiotic exposure. Of the long list of antibiotics associated with elevated INR, quinolones (e.g. ciprofloxacin, levofloxacin), trimethoprim-sulfamethoxazole, macrolides (e.g. azithromycin), and azole antifungals (e.g. fluconazole) are generally thought to carry the highest risk of warfarin toxicity, while amoxacillin and cephalexin may be associated with a more modest risk. 1-3

Other drugs such as amiodarone (Did she have atrial fibrillation during her recent hospitalization?), acetaminophen (Has she been receiving at least 2 g/day for several consecutive days?), and increasing dose of levothyroxine (Was she thought to be hypothyroid recently?) should also be considered.3,4

Also remember to ask about herbal supplements (eg, boldo-fenugreek, dong quai, danshen) that may potentiate the effect of warfarin. 3 Of course, poor nutrition in the setting of recent illness might have also played a role.5

As far as the mechanisms for drug interaction with warfarin, some drugs act as cytochrome p450 inhibitors (thus reducing the metabolism of warfarin), while others influence the pharmacodynamics of warfarin by inhibiting the synthesis or increasing the clearance of vitamin K-2 dependent coagulation factors.3

Antibiotics may increase the risk of major bleeding through disruption of intestinal flora that synthesize vitamin K-2 with or without interference with the metabolism of warfarin through cytochrome p450 isozymes inhibition.

Check out a related pearl on P4P: https://pearls4peers.com/2015/06/25/is-there-anyway-to-predict-a-significant-rise-in-inr-from-antibiotic-use-in-patients-who-are-also-on-warfarin  

 

References

  1. Baillargeon J, Holmes HM, Lin Y, et al. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med. 2012 February ; 125(2): 183–189. https://www.ncbi.nlm.nih.gov/pubmed/22269622
  2. Juurlink DN. Drug interactions with warfarin: what every physician should know. CMAJ, 2007;177: 369-371. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1942100/pdf/20070814s00018p369.pdf
  3. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292.  https://www.ncbi.nlm.nih.gov/pubmed/22315269
  4. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on international normalized ratio in patients receiving warfarin therapy. Pharmacotherapy 2011;31:591-7. https://www.ncbi.nlm.nih.gov/pubmed/21923443
  5. Kumar S, Gupta D, Rau SS. Supratherapeutic international normalized ratio: an indicator of chronic malnutrition due to severely debilitating gastrointestinal disease. Clin Pract. 2011;1:e21. doi:10.4081/cp.2011.e21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981245

 

Contributed by Rachel Weitzman, Medical Student, Harvard Medical School, Boston, MA.

My elderly patient on chronic warfarin with recent hospitalization for soft tissue infection is now readmitted with gastrointestinal bleed and a newly-discovered supra-therapeutic INR? Why did her INR jump?

In my patient with sepsis, is administration of proper antibiotics within an hour compared to 1-3 hours associated with better outcome?

The weight of the evidence based on observational studies suggests that the earlier the antibiotics are administered even within the first 3 hrs of the diagnosis of sepsis,  the better the patient outcome.

A 2017 study analyzing data from 37 studies (primarily observational) involving ~20,000 patients with severe sepsis and/or shock found a 10% increase in hospital mortality for every 1 hr delay in initiation of antibiotic therapy1. Two multicenter studies (1 in Pennsylvania2 and another in California3) and a New York State data base study involving patients with severe sepsis or septic shock4 similarly reported decreased survival with each 1- hr delay in antibiotic therapy. Another study of patients with severe sepsis found that each hour delay in first antibiotic dose administration was associated with an 8% increased risk of progression to shock5.

Despite the emphasis on the timing of the first dose of antibiotics, let’s not forget that the second dose of antibiotics should also be given on time in sepsis; a >25% delay is associated with increased mortality, length of stay and requirement for mechanical ventilation6.

So, yes, antibiotics should be given within 3 hours of diagnosis of sepsis, but within an hour followed by a timely second dose is even better!

Final Pearl: Did you know that sepsis is the 3rd leading cause of death in the US and contributes to 1 in every 2 to 3 hospital deaths7?

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References

  1. Kalil AC, Johnson DW, Lisco SJ, et al. Early goal-directed therapy for sepsis: a novel solution for discordant survival outcomes in clinical trials. Crit Care Med 2017;45:607-14. https://www.ncbi.nlm.nih.gov/pubmed/28067711
  2. Seymour CW, Kahn JM, Martin-Gill, et al. Delays from first medical contact to antibiotic administration for sepsis. Crit Care Med 2017;45:759-65. https://insights.ovid.com/pubmed?pmid=28234754
  3. Liu VX, Fielding-Singh V, Greene JD, et al. Th timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit care Med 2017; 196;858-63. https://www.ncbi.nlm.nih.gov/pubmed/28345952
  4. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376:2235-44. http://www.nejm.org/doi/full/10.1056/NEJMoa1703058
  5. Whiles BB, Deis AS, Simpson SQ. Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med 2017; 45:623-29. https://www.ncbi.nlm.nih.gov/pubmed/28169944
  6. Leisman D, Huang V, Zhou Q, et al. Delayed second dose antibiotics for patients admitted from the emergency department with sepsis: prevalence, risk factors, and outcomes. Crit Care Med 2017;45:956-65. https://www.ncbi.nlm.nih.gov/pubmed/28328652
  7. https://www.ecri.org/components/HRC/Documents/Sepsis%20at%20a%20Glance.pdf

 

 

In my patient with sepsis, is administration of proper antibiotics within an hour compared to 1-3 hours associated with better outcome?

Why are patients with cirrhosis and upper gastrointestinal bleed routinely treated with antibiotics?

Cirrhotic patients with upper gastrointestinal bleed (UGIB) are at high risk of bacterial infections: 22% during the first 48 h after admission, 35-66% within 2 weeks of initial bleeding1. Antibiotic prophylaxis has been shown to reduce short term mortality, bacterial infections, early rebleeding and volume of blood transfused1-4.

But what is the exact connection between UGIB and bacterial infections in cirrhosis? One hypothesis is that UGIB sets up the host for bacterial infection via translocation (eg, due to hypovolemia), procedures necessary in the management of bleeding (eg endoscopy, sclerotherapy, IV access), and aspiration pneumonia. More intriguing is the reverse hypothesis—that is the bacterial infection serves as a trigger for UGIB.  Several lines of evidence support this view1,2.

  • Cirrhotic patients admitted for non-UGIB-related conditions may be 4x more likely to develop UGIB during their hospitalization in the presence of bacterial infection on admission4
  • Infections predispose to early variceal rebleeding
  • Infection/endotoxemia increase portal pressure, and impair liver function and coagulation
  • Commonly cited risk factors for variceal bleeding (eg, hepatic venous pressure gradient, liver function, size of varices) do not readily explain why bleeding occurs unpredictably and why despite daily increases in portal pressure (eg, following daily meals and exercises), UGIB is relatively infrequent.

 

References

  1. Thalheimer U, Triantos CK, Samonakis DN, et al. Infection, coagulation, and variceal bleeding in cirrhosis. Gut 2005;54:556-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774431
  2. Goulis J. Bacterial infection in the pathogenesis of variceal bleeding. Is there any role for antibiotic prophylaxis in the cirrhotic patient. Ann Gastroenterol 2001;14:205-11. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&ved=0ahUKEwjNh-rhlpLVAhXGdD4KHSurANcQFgg4MAM&url=http%3A%2F%2Fwww.annalsgastro.gr%2Findex.php%2Fannalsgastro%2Farticle%2Fdownload%2F80%2F71&usg=AFQjCNHJfAyYAjuNXpwsWGrVuyuxxgJYKg
  3. Soares-Weiser K, Brezis, Tur-Kaspa R, et al. Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials. Scand J Gastroenterol 2003;38:193-200. http://www.tandfonline.com/doi/abs/10.1080/00365520310000690
  4. Anastasioua J, Williams R. When to use antibiotics in the cirrhotic patient? The evidence base. Ann Gastroenterol. 2013; 26(2): 128–131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959942
  5. Benavides J, Fernandez N, Colombato L, et al. Further evidence linking bacterial infection and upper G.I. bleeding in cirrhosis. Results from a large multicentric prospective survey in Argentina. J Hepatol 2003;38 (suppl 2):A176. http://www.journal-of-hepatology.eu/article/S0168-8278(03)80592-5/abstract

 

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Why are patients with cirrhosis and upper gastrointestinal bleed routinely treated with antibiotics?

Should I order serum procalcitonin on my patient with suspected infection?

Two things to ask before you order procalcitonin (PCT): 1. Will it impact patient management?; and 2. If so, will the result be available in a timely manner ie, within hours not days?

Whatever the result, PCT should always be interpreted in the context of the patient’s illness and other objective data. Not surprisingly then, as a “screening” test, PCT may be more useful in patients with low pre-test likelihood of having bacterial infection, not dissimilar to the use of D-dimer in patients with low pre-test probability of pulmonary embolism1.  

Several potential clinical uses of this biomarker have emerged in recent years,  including:1,2

  • Helping decide when to initiate antibiotics in patients with upper acute respiratory tract infections and bronchitis. A normal or low PCT supports viral infection.
  • Helping decide when to discontinue antibiotics (ie, when PCT normalizes) in community-acquired or ventilator-associated pneumonia.
  • Helping monitor patient progress with an expected drop in PCT of about 50% per day (half-life ~ 24 hrs) with effective therapy.

Few caveats…

  • PCT may be unremarkable in about a third of patients with bacteremia (especially due to less virulent bacteria, including many gram-positives)3.  
  • PCT levels are lowered by high-flux membrane hemodialysis, so check a baseline level before, not after, hemodialysis4.
  • Lastly, despite its higher specificity for bacterial infections compared to other biomarkers such as C-reactive protein, PCT may be elevated in a variety of non-infectious conditions, including pancreatitis, burns, pulmonary edema or aspiration, mesenteric infarction (ischemic bowel), cardiogenic shock, and hypotension during surgery2.

 

References:

  1. Schuetz P, Muller B, Chirst-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections (review). Evid-Based Child Health (A Cochrane Review Journal) 2013;8:4;1297-137. http://onlinelibrary.wiley.com/doi/10.1002/ebch.1927/pdf
  2. Gilbert GN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897488/pdf/0655-10.pdf
  3. Yan ST, Sun LC, Jia HB. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med 2017;35:779-83. https://www.ncbi.nlm.nih.gov/m/pubmed/27979420/#fft
  4. Grace E, Turner RM. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin Infect Dis 2014;59:1761-7. https://www.ncbi.nlm.nih.gov/pubmed/25228701
Should I order serum procalcitonin on my patient with suspected infection?

What are some of the major changes in the 2016 Infectious Diseases Society of America and the American Thoracic Society guidelines on pneumonia in hospitalized patients?

The most noticeable change is the elimination of the concept of health-care associated pneumonia (HCAP) altogether1. This action is in part related to the fact that many patients with HCAP were not at high risk for multi-drug resistant organisms (MDROs) , and that individual patient risk factors, not mere exposure to healthcare facilities, were better determinant of  the need for broader spectrum antimicrobials.

Other noteworthy points in the guidelines include:

  • Although hospital-associated pneumonia (HAP) is still defined as a pneumonia not incubating at the time of admission and occurring 48 hrs or more following hospitalization, it now only refers to non-VAP cases; VAP cases are considered a separate category.
  • Emphasis is placed on each hospital generating antibiograms to guide providers with respect to the optimal choice of antibiotics.
  • Despite lack of supportive evidence, the guidelines recommend obtaining respiratory samples for culture in patients with HAP.
  • Prior intravenous antibiotic use within 90 days is cited as the only consistent risk factor for MDROs, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas sp.

 

Reference

  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.  Advance Access published July 14, 2016. https://www.ncbi.nlm.nih.gov/pubmed/27418577
What are some of the major changes in the 2016 Infectious Diseases Society of America and the American Thoracic Society guidelines on pneumonia in hospitalized patients?

Is oral vancomycin prophylaxis (OVP) effective in preventing recurrent Clostridium difficile infection (CDI) in patients requiring systemic antimicrobial therapy (SAT)?

Although OVP is often administered to patients with history of CDI who require SAT, evidence to support this practice has been lacking until recently.

In a 2016 retrospective study of 203 patients with prior history of CDI, those who received OVP (125 mg or 250 mg 2x/daily) during the course of their SAT and for up to 1 week thereafter were significantly less likely to have a recurrence than the non-OVP group (4.2% vs 26.6%, respectively, O.R. 0.12 [C.I. 0.04-0.4]) (1). In this study, the mean interval between prior CDI and initiation of prophylaxis was 6.1 months (1-21 months), and the mean duration of prophylaxis following discontinuation of SAT was 1 day (0-6 days). Similar results have been reported by others (2,3).

Despite their retrospective nature, these studies lend support to the use of OVP in reducing the risk of recurrent CDI in patients who require SAT. It is unclear how long OVP should be continued after SAT is completed, if at all, but common practice is 1-2 weeks.

A randomized-controlled study comparing OVP 125 mg daily for the duration of SAT plus 5 days vs placebo appears to be on the way (4)!

References

  1. Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of oral vancomycin in preventing recurrent Clostridium difficile infection in patients treated with systemic antimicrobial agents. Clin Infect Dis 2016; Advance Access published June 17, 2016. Doi.10.1093/cid/ciw401.
  2. Carignan A, Sebastien Poulin, Martin P, et al. Efficacy of secondary prophylaxis with vancomycin for preventing recurrent Clostridium difficile infections. Am J Gastroenterol 2016;111: 1834-40. https://www.ncbi.nlm.nih.gov/pubmed/27619835
  3. Granetsky A, Han JH, Hughes ME, et al. Oral vancomycin is highly effective in preventing Clostridium difficile infection in allogeneic hematopoietic stem cell transplant recipients. Blood 2016;128:2225; http://www.bloodjournal.org/content/128/22/2225?sso-checked=true
  4. https://clinicaltrials.gov/ct2/show/NCT03462459

Disclosure: The author of this post was also a co-investigator of one of the studies cited (ref. 1).

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Is oral vancomycin prophylaxis (OVP) effective in preventing recurrent Clostridium difficile infection (CDI) in patients requiring systemic antimicrobial therapy (SAT)?

In hospitalized patients with community-acquired pneumonia (CAP), has empiric treatment with beta-lactam plus macrolide or a quinolone been shown to be superior to beta-lactam monotherapy ?

Actually no!

In fact, a 2015 study of CAP from Netherlands, published in New England Journal of Medicine, demonstrated that empiric treatment with beta-lactam monotherapy was not inferior to strategies using a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality, or length of hospital stay (1). To help exclude Legionella pneumonia (often accounting for <5% of CAP[2]), urine Legionella antigen was routinely performed in this study.

So once Legionella has been reasonably excluded, unless suspicion for other atypical causes of CAP (i.e. Mycoplasma pneumoniae or Chlamydophila pneumoniae) remains high, empiric monotherapy with a beta-lactam (e.g. ceftriaxone) may be just as effective in many cases of CAP.

References

1. Postma DF1, van Werkhoven CH, van Elden LJ, et al. CAP-START Study Group Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372:1312-23.  https://www.ncbi.nlm.nih.gov/pubmed/25830421  

2. von Baum H, Ewig S, Marre R, et al. Competence Network for Community Acquired Pneumonia Study Group. Community-acquired Legionella pneumonia: new insights from the German competence network for community acquired pneumonia. Clin Infect Dis 2008;46:1356. https://www.ncbi.nlm.nih.gov/pubmed/18419436

Contributed by Jessica A. Hennessey, MD, PhD, Mass General Hospital, Boston, MA

In hospitalized patients with community-acquired pneumonia (CAP), has empiric treatment with beta-lactam plus macrolide or a quinolone been shown to be superior to beta-lactam monotherapy ?