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?

When should surgery be considered in my hospitalized patient with divertculitis?

Severe diffuse abdominal pain, fever, tachycardia, leukocytosis or other signs of sepsis and diffuse peritonitis indicative of free perforation requires emergent surgery. Urgent surgery should be considered when your patient fails to improve (eg, abdominal pain or the inability to tolerate enteral nutrition, bowel obstruction, or infection-related ileus) despite medical therapy or percutaneous drainage. 1,2

Lower threshold for surgical intervention is also needed in transplant patients, patients on chronic corticosteroid therapy, other immunosuppressed patients and those with chronic renal failure or collagen-vascular disease because these patients have a significantly greater risk of recurrent, complicated diverticulitis requiring emergency surgery. Overall, up to 20% of patients with acute diverticulitis undergo surgery during the same hospitalization.2

For patients with recurrent uncomplicated diverticulitis, decision regarding future elective surgery should be individualized. Although older guidelines recommended surgery after 2 attacks of uncomplicated diverticulitis, more recent guidelines place less emphasis on the number of episodes and stress the importance of considering the severity of the attacks, chronic or lingering symptoms, inability to exclude carcinoma, overall medical condition of the patient, risks of surgery, and the impact of diverticulitis on the patient’s lifestyle.1,2

Of interest, a decision analysis model suggests that elective resection after a fourth episode may be as safe as earlier resection.3

 

References

  1. Young-Fadok TM. Diverticulitis. N Eng J Med 2018;397:1635-42 https://www.nejm.org/doi/full/10.1056/NEJMcp1800468
  2. Feingold D, Steele SM, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum 2014;57:284-94. https://www.fascrs.org/sites/default/files/downloads/publication/practice_parameters_for_the_treatment_of_sigmoid.2.pdf
  3. Salem L, Veenstra DL, Sullivan SD, et al. The timing of elective colectomy in diverticulitis: A decision analysis. J Am Coll Surg 2004;199:904-12. https://www.journalacs.org/article/S1072-7515(04)01000-2/fulltext

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When should surgery be considered in my hospitalized patient with divertculitis?

Should I use qSOFA to screen for severe infections in my non-ICU patient?

Sepsis-3 qSOFA criteria—systolic BP ≤100 mg Hg, altered mental state, and RR≥22, with ≥2 considered positive— should NOT be used as either a screening or diagnostic tool for sepsis until properly designed prospective studies validate its utility.1

An important issue with qSOFA is its poor sensitivity for identifying patients with sepsis and its complications.  In a retrospective study of over 30,000 hospitalized patients suspected of infection in the emergency department or hospital wards, qSOFA ≥2 had a sensitivity of only 54% and specificity of 67% for in-hospital mortality or ICU transfer vs a much higher sensitivity of 91% but lower specificity of 13% for SIRS ≥2. Interestingly, most patients in this study met qSOFA criteria only 5 h before the studied outcome vs 17 h for SIRS ≥2 criteria.2

In another retrospective study of over 15,000 patients presenting to the Emergency Department with suspected infection, qSOFA ≥2 had a sensitivity of  49% and a specificity of 79% for hospital mortality vs  84% and 35% for SIRS≥2, and 65% and 74% for “severe sepsis” (Sepsis-2), respectively.3

So, using qSOFA alone to decide who needs prompt management of their infection (eg, blood cultures, serum lactate, antibiotics, fluids) may delay timely intervention in a substantial proportion of patients with infection that may become complicated by ICU transfer or death.  As is usually the case in medicine, it pays to look at the entire picture!

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References

  1. Machado FR, Nsutebu E, AbDulaziz S, et al. Sepsis 3 from the perspective of clinicians and quality improvement initiatives. J Crit Care 2017:40: 315-17. https://www.ncbi.nlm.nih.gov/pubmed/28478045
  2. Churpek MM, Synder A, Han X, et al. Quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration n infected patients outside the intensive care unit. Am J Respir Crit Care Med 2017; 195: 906-11. https://www.ncbi.nlm.nih.gov/pubmed/27649072
  3. Lembke K, Parashar S, Simpson S. Sensitivity and specificity of SIRS, qSOFA, and severe sepsis for mortality of patients presenting to the emergency department with suspected infection. Chest Annual Meeting, Toronto, October 29, 2017. http://dx.doi.org/10.1016/j.chest.2017.08.427

 

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!

Should I use qSOFA to screen for severe infections in my non-ICU patient?