“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?”

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?”

Is cefepime an acceptable alternative to carbapenems in the treatment of cefepime susceptible extended spectrum beta-lactamase (ESBL) Gram-negatives?

Irrespective of in-vitro susceptibility results, cefepime should be avoided in the treatment of serious ESBL infections associated with bacteremia, pneumonia, intraabdominal infection, endocarditis, bone/joint infection or whenever a high bacterial inoculum is suspected. Cefepime should be considered only in non-severe infections (eg, uncomplicated urinary tract infection) when the minimum inhibitory concentration (MIC) is 2 mg/L or less (1).

 

To date, clinical studies comparing cefepime vs carbapenem have been small and/or retrospective, often with conflicting results (1). A 2016 propensity score-matched study of patients with ESBL bacteremia receiving cefepime therapy followed by carbapenem therapy vs carbapenem for the entire treatment duration found higher 14 day mortality in the cefepime group (41% vs 20% in the carbapenem group) (2).  Of note, 2 of the patients receiving cefepime who died were infected with an ESBL organism with MIC of 1 mcg/mL. 

 

Another study found cefepime to be inferior to carbapenem therapy in ESBL bacteremic patients with better outcome when cefepime MIC was 1 ug/m or less (3).

 

Two studies involving patients with ESBL UTIs found no significant difference between cefepime and carbapenem in clinical and microbiological response or in-hospital mortality, while another UTI study with a high rate of septic shock (33%) found that cefepime was inferior to carbapenem in clinical and microbiological response (2).

 

The diminished efficacy of cefepime for the treatment of ESBL infections may be related to its “inoculum effect” ie, marked increase in MIC with increased inoculum size compared to that used in standard laboratory susceptibility testing (1,4).   

 

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References

  1. Karaiskos I, Giamarellou H. Carbapenem-sparing strategies for ESBL producers: when and how. Antibiotics 2020;9,61. https://pubmed.ncbi.nlm.nih.gov/32033322/
  2. Wang R, Cosgrove S, Tschudin-Sutter S, et al. Cefepime therapy for cefepime-susceptible extended-spectrum beta-lactamase-producing Enerobacteriaceae bacteremia. Open Forum Infect Dis 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942761/
  3. Lee NY, Lee CC, Huang WH, et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 203;56:488-95. https://academic.oup.com/cid/article/56/4/488/351224
  4. Smith KP, Kirby JE. The inoculum effect in the era of multidrug resistance:minor differences in inoculum have dramatic effect on MIC determination. Antimicrob Agents Chemother 2018;62:e00433-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105823/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. 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!

Is cefepime an acceptable alternative to carbapenems in the treatment of cefepime susceptible extended spectrum beta-lactamase (ESBL) Gram-negatives?

Should I consider fosfomycin in the treatment of urinary tract infection in my male patient with suspected prostatitis?

Although fosfomycin (FM) has been approved by the FDA only for the treatment of uncomplicated urinary tract infection (UTI) in women, it may also have a role in the treatment of acute and chronic prostatitis among males given its favorable levels in the prostate tissue. 1-5

Despite lack of studies comparing the efficacy of FM with that of commonly used antibiotics for treatment of prostatitis, the potential utility of FM is supported by several reports of its efficacy in the treatment of prostatitis, including those caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative rods. 1,4-5

When considering FM for treatment of prostatitis, a higher dose than customary may be needed (3 g once daily, not every 48-72 h) . 4 Although the optimal duration of therapy with FM is unclear in this setting, 12-16 weeks of therapy was used in 2 patients with recurrent UTIs and prostatitis due to multi-drug resistant ESBL-positive E. coli. 4

Given its pharmacokinetics and lack of proven efficacy, avoid FM in pyelonephritis, perinephric abscess or UTI with bacteremia. 2

References

  1. Falagas ME, Vouloumanou EK, Samonis G, et al. Fosfomycin. Clin Microbiol Rev 2016;29:321-347. https://www.ncbi.nlm.nih.gov/pubmed/26960938
  2. Wankum M, Koutsari C, Gens K. Fosfomycin use. Pharmacy Times. November 30, 2017. https://www.pharmacytimes.com/publications/health-system-edition/2017/november2017/fosfomycin-use
  3. Cunha BA, Gran A, Raza M. Persistent extended-spectrum β-lactamase-positive Escherechia coli chronic prostatitis successfully treated with a combination of fosfomycin and doxycycline. International J Antimicrob Agents 2015;45:427-29. https://www.ncbi.nlm.nih.gov/pubmed/25662814
  4. Grayson ML, Macesic N, Trevillyan J, et al. Fosfomycin for treatment of prostatitis: new tricks for old dogs. Clin Infect Dis 2015;61:1141-3. https://www.ncbi.nlm.nih.gov/pubmed/26063723
  5. Falagas ME, Rafailidis PI. Fosfomycin: the current status of the drug. Clin Infect Dis 2015;61:1144-6. https://www.ncbi.nlm.nih.gov/pubmed/26063717
Should I consider fosfomycin in the treatment of urinary tract infection in my male patient with suspected prostatitis?