Should I choose a bactericidal over bacteriostatic antibiotic in the treatment of my patient with pneumonia complicated by bacteremia?

You don’t have too!  Although “bacteriostatic” antibiotics have traditionally been regarded as inferior to “bactericidal” antibiotics in the treatment of serious infections, a 2018 “myth busting” systemic literature review1 concluded that bacteriostatic antibiotics are just as effective against a variety of infections, including pneumonia, non-endocarditis bacteremia, skin and soft tissue infections and genital infections; no conclusion can be made in regards to endocarditis or bacterial meningitis, however, due insufficient clinical evidence.1-3

Interestingly, most of the studies included in the same systemic review showed that bacteriostatic antibiotics were more effective compared to bactericidal antibiotics.1 So, for most infections in hospitalized patients, including those with non-endocarditis bacteremia, the choice of antibiotic among those that demonstrate in vitro susceptibility should not be based on their “cidal” vs “static” label.

Such conclusion should not be too surprising since the definition of bacteriostatic vs bactericidal is based on arbitrary in vitro constructs and not validated by any available in vivo data. In addition, static antibiotics may kill bacteria as rapidly as cidal antibiotics in vitro at higher antibiotic concentrations.3

Another supportive evidence is a 2019 study finding similar efficacy of sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteremia compared to continued IV antibiotic therapy despite frequent use of bacteriostatic oral antibiotics (eg, linezolid, clindamycin and doxycycline). 4

 

References

  1. Wald-Dickler N, Holtom P, Spellberg B. Busting the myth of “static vs cidal”: as systemic literature review. Clin Infect Dis 2018;66:1470-4. https://academic.oup.com/cid/article/66/9/1470/4774989
  2. Steigbigel RT, Steigbigel NH. Static vs cidal antibiotics. Clin Infect Dis 2019;68:351-2. https://academic.oup.com/cid/article-abstract/68/2/351/5067395
  3. Wald-Dickler N, Holtom P, Spellberg B. Static vs cidal antibiotics; reply to Steigbigel and Steigbigel. Clin Infect Dis 2019;68:352-3. https://academic.oup.com/cid/article-abstract/68/2/352/5067396?redirectedFrom=fulltext
  4. Jorgensen SCJ, Lagnf AH, Bhatia S, et al. Sequential intravenous-to-oral outpatient antbiotic therapy for MRSA bacteraemia: one step closer.  J Antimicrob Chemother 2019;74:489-98.  https://www.ncbi.nlm.nih.gov/pubmed/30418557

 

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Should I choose a bactericidal over bacteriostatic antibiotic in the treatment of my patient with pneumonia complicated by bacteremia?

Is clindamycin an acceptable empiric monotherapy for Staphylococcus aureus (SA) infections in adults?

Clindamycin is active in-vitro against many strains of SA and is indicated in the treatment of SA mild-to-moderate skin and soft tissue infections (SSTIs), including some methicillin-resistant strains 1,2.  However, evidence for its use as monotherapy against SA infections in other body sites is limited or lacking.   For example, in adults with pneumonia, efficacy of clindamycin is based solely on case series that excluded monotherapy3.  For bone and joint infections, clindamycin has limited evidence of efficacy in adults, and is not recommended in the treatment of endovascular or central nervous system infections2.

 Emergence of resistance to clindamycin in previously susceptible SA isolates may also occur during therapy conferred by erythromycin resistance methylase (erm) gene which is typically screened for by the “D-zone” test2 (Figure).  Increasing resistance of SA to clindamycin has led to recommendation against its empiric use for severe or complicated SSTIs (e.g. large abscess or deep infections)4.  

dzoneclindapcrop

Fig. The “E” disk (on left) contains erythromycin; “CC” disk (on right) contains clindamycin. The test detects inducible clindamycin resistance in erythromycin-resistant , clindamycin- susceptible isolates (http://www.cdc.gov/groupbstrep/images/lab-positivegbs-lg.jpg).

References:

  1. Miller LG, Daum RS, Creech CB, Young D, Downing MD, Eells SJ, Pettibone S, Hoagland RJ, Chambers HF. Clindamycin versus trimethoprim–sulfamethoxazole for uncomplicated skin infections. N Engl J Med 2015;372:1093-103. 
  2. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Rybak MJ. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011;52:e18-55. 
  3. Lobo LJ, Reed KD, Wunderink RG. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest 2010; 138:130-6. 
  4. VanEperen AS, Segreti J. Empirical therapy in Methicillin-resistant Staphylococcus Aureus infections: An Up-To-Date approach. J Infect Chemother 2016;22:351-9.

Contributed by Nathan T. Georgette, 4th year, Harvard Medical School student

 

Is clindamycin an acceptable empiric monotherapy for Staphylococcus aureus (SA) infections in adults?