Anaerobes;

“I go after Streptococcus pneumoniae and many other bacteria causing community-acquired pneumonia with vengeance but lately I have had a hard time keeping up with many gram-negatives, including some E. coli. Who am I?”

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Additional hint: “The latest FDA warning against the use of my class of drugs has to do with increased risk of ruptures or tears in the aorta in certain patients, including the elderly and those with hypertension, aortic aneurysm or peripheral vascular disease.” 

Editor’s note: This post is part of the P4P “Talking Therapeutics” series designed to make learning about antibiotics fun. Individual antibiotics give a short description of themselves and you are asked to guess their names. Antimicrobial spectrum, common uses and potential adverse effects follow. Enjoy!

And the answer is…… HERE

Selected antimicrobial spectrum

                Gram-positives: Streptococcus pneumoniae, Staphylococcus aureus                         (some resistance even in MSSA), Enterococcus spp (urine;some resistance)

                Gram-negatives: Enterics (eg, E. coli, Klebsiella spp), Pseudomonas spp,                                 Stenotrophomonas maltophilia, H. influenzae, some ESBLs.

                 AVOID: MRSA, anaerobes

Common clinical uses: community-acquired pneumonia (CAP), healthcare-associated pneumonia (HAP), urinary tract infections (UTIs), legionnaire’s disease, abdominal infection (plus anaerobic coverage)

WATCH OUT! QT prolongation, C. difficile, central nervous system toxicity, seizures, myasthenia gravis, peripheral neuropathy, tendinopathy, drug interactions (eg. warfarin), and most recently aortic aneurysm diagnosis/dissection!

Remember the key features of levofloxacin before you prescribe it!

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Selected references

  1. FDA. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients.  https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics. Accessed Nov 26, 2020,.
  2. Marangon FB, Miller D, Muallem MS, et al. Ciprofloxacin and levofloxacin resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis. Am J Ophthal 2004;137:453-58. https://www.ajo.com/article/S0002-9394(03)01287-X/pdf
  3. Yasufuku T, Shigemura K, Shirakawa T, et al. Mechanisms of and risk factors for fluoroquinolone resistance in clinical Enterococcus faecalis from patients with urinary tract infections. J Clin Microbiol 2011;49:3912-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209098/
  4.  Rawla P, Helou MLE, Vellipuram AR. Fluoroquinolones and the risk of aortic aneurysm or aortic dissection: A systematic review and meta-analysis. Cardiovasc Hematol Agents Med Chem 2019;17:3-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865049/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

“I go after Streptococcus pneumoniae and many other bacteria causing community-acquired pneumonia with vengeance but lately I have had a hard time keeping up with many gram-negatives, including some E. coli. Who am I?”

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

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

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?

FA Manian MD, MPH, , , , , , , , , Leave a comment

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?

My patient with cirrhosis now has an upper gastrointestinal bleed (UGIB) with hepatic encephalopathy (HE). What’s the connection between UGIB and HE?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Hepatic encephalopathy (HE) may be precipitated by a variety of factors including infection, hypovolemia, electrolyte imbalance (eg, hyponatremia, hypokalemia), metabolic alkalosis, sedatives, and of course UGIB. 1-3

Ammonia is often considered to play a central role in the the pathogenesis of HE, particularly when associated with UGIB. The ammoniagenic potential of UGIB is primarily attributed to the presence of hemoglobin protein in the intestinal tract. One-half of the ammoniagenesis originates from amino acid metabolism (mainly glutamine) in the mucosa of the small bowel, while the other half is due to the splitting of urea by the resident bacteria in the colon (eg, Proteus spp., Enterobacteriaceae, and anerobes).1,2

A large protein load in the GI tract, as occurs in UGIB, may result in hyperammonemia in patients with cirrhosis due to the limited capacity of the liver to convert ammonia to urea through the urea cycle as well as by the shunting of blood around hepatic sinusoids. Recent studies, however, also implicate the kidneys as an important source of ammonia in this setting, further compounding HE.3

It’s important to stress that ammonia is not likely to be the only mediator of HE. Enhanced production of cytokines due to infection or other inflammatory states, neurosteroids, endogenous benzodiazepines, and other bacterial byproducts may also play an important role in precipitating HE.2,4-6  So stay tuned!

Bonus pearl: Did you know that proinflammatory cytokines tumor necrosis factor-alpha and inerleukin-6 increase ammonia permeability across central nervous system-derived endothelial cells? 7

 

References

  1. Olde Damink SWM, Jalan R, Deutz NEP, et al. The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. Hepatology 2003;37:1277-85.
  2. Frederick RT. Current concepts in the pathophysiology and management of hepatic encephalopathy. Gastroenterol Hepatol 2011;7:222-233.
  3. Tapper EB, Jiang ZG, Patwardhan VR. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy. Mayo Clin Proc 2015;90:646-58.
  4. Shawcross DL, Davies NA, Williams R, et al. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 2004;40:247-254.
  5. Shawcross DL, Sharifi Y, Canavan JB, et al. Infection and systemic inflammation, not ammonia, are associated with grade ¾ hepatic encephalopathy, but not mortality in controls. J Hepatol 2011;54:640-49.
  6. Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation.Cell Mol Life Sci 2005;62:2295-2304.
  7. Duchini A, Govindarajan S, Santucci M, et al. Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells. J Investig Med 1996;44:474-82.

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My patient with cirrhosis now has an upper gastrointestinal bleed (UGIB) with hepatic encephalopathy (HE). What’s the connection between UGIB and HE?

How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)?

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

Since the primary reason for obtaining a sputum culture in a patient with pneumonia is to sample the lower respiratory tract, you should first verify that the sputum was “adequate” by reviewing the gram stain. Absence of neutrophils (unless the patient is neutropenic) with or without epithelial cells on gram stain of sputum suggests that it may not be an adequate sample (ie, likely saliva)1, and therefore growth of normal respiratory flora (NRF) should not be surprising in this setting.  

Other potential explanations for NRF on sputum culture in patients with CAP include:2-5

  • Delay in sputum processing with possible overgrowth of oropharyngeal flora.
  • Pneumonia caused by pathogens that do not grow on standard sputum culture media (eg, atypical organisms, viruses, anaerobes).
  • Pneumonia caused by potential pathogens such as as Streptococcus mitis and Streptococcus anginosus group that may be part of the NRF.
  • Initiation of antibiotics prior to cultures (eg, in pneumococcal pneumonia).

Of note, since 2010, several studies have shown that over 50% of patients with CAP do not have an identifiable cause.3 So, growing NRF from sputum of patients with CAP appears to be common.

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References

  1. Wong LK, Barry AL, Horgan SM. Comparison of six different criteria for judging the acceptability of sputum specimens. J Clin Microbiol 1982;16:627-631. https://www.ncbi.nlm.nih.gov/pubmed/7153311
  2. Donowitz GR. Acute pneumonia. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (2010). Churchill Livingstone, pp 891-916.
  3. Musher DM, Abers MS, Bartlett JG. Evolving understanding of the causes of pneumonia in adults, with special attention to the role of pneumococcus. Clin Infect Dis 2017;65: 1736-44. https://www.ncbi.nlm.nih.gov/pubmed/29028977
  4. Abers MS, Musher DM. The yield of sputum culture in bacteremic pneumococcal pneumonia after initiation of antibiotics. Clin Infect Dis 2014; 58:1782. https://www.ncbi.nlm.nih.gov/pubmed/24604901
  5. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Bartlett JG, Gorbach SL, Finegold SM. Am J Med 1974;56:202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)?