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?

Should we routinely cover for methicillin-resistant Staphylococcus aureus (MRSA) when treating patients for cellulitis?

No! Despite the MRSA epidemic, β-hemolytic streptococci (BHS) are still considered the primary cause of non-purulent cellulitis (e.g. without abscesses, or infections involving deep soft tissues, wounds, or ulcer).

In a prospective study of patients admitted to the hospital for “diffuse,  non-culturable “(i.e. many of our patients), most had serological evidence of acute  BHS, and >95% responded to a β-lactam antibiotic treatment (1) . 

The current Infectious Diseases Society of America guidelines do not endorse empiric coverage of  MRSA for non-purulent cellulitis,  unless there is systemic toxicity or poor response to  β-lactam  monotherapy (2). More specifically, the guidelines recommend a  β-lactam antibiotic for treatment of non-purulent cellulitis in hospitalized patients with modification to MRSA coverage if no clinical response.

One advantage to β-lactam monotherapy is the ease of switch to an equivalent oral antibiotic (e.g. cephalexin) when transitioning from parenteral antibiotic therapy.  

References

1. Jeng A, Beheshti M, Li J, et al. The role of beta-hemolytic streptococci in causing diffuse nonculturable cellulitis: a prospective investigation. Medicine (Baltimore) 2010;89:217-26. https://www.ncbi.nlm.nih.gov/pubmed/20616661

2. Liu C, Bayer A, Cosgrove SE, et al. 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. https://www.ncbi.nlm.nih.gov/pubmed/21208910

 

Should we routinely cover for methicillin-resistant Staphylococcus aureus (MRSA) when treating patients for cellulitis?

My patient with foot osteomyelitis due to methicillin-sensitive Staphylococcus aureus (MSSA) is ready to go home on IV antibiotic therapy. Is daily ceftriaxone therapy an appropriate option?

Yes, it appears to be!  Ceftriaxone is active against MSSA and may be an option for treatment of infections due to this organism at least in certain situations.  

In a retrospective study comparing ceftriaxone to oxacillin for osteoarticular infections due to MSSA, there was no difference in treatment success at 3-6 and > 6 months following completion of IV antibiotics; oxacillin had to be discontinued more often due to toxicity, however (1).    

In another retrospective study comparing cefazolin to ceftriaxone for treatment of MSSA infections ( ≥50% of patients with osteomyelitis),  favorable outcomes, adverse events and complications were similar between the 2 groups (2). 

Several other studies have reported no significant difference in treatment failure between cefazolin and ceftriaxone in MSSA infections (3).  A smaller retrospective study, however, reported higher rate of treatment failure (defined to include unplanned extension of parenteral therapy) with ceftriaxone in MSSA bacteremia without finding any difference in time to blood culture clearance, or rates of persistent bacteremia, relapse after treatment, achievement of source control, mortality or readmission (3).

References

1. Wieland BW, Marcantoni JR, Bommarito KM, et al. A retrospective comparison of ceftriaxone versus oxacillin for osteoarticular infections due to methicillin-susceptible Staphylococcus aureus. Clin Infect Dis 2012;54:585-590. https://www.ncbi.nlm.nih.gov/pubmed/22144536

2.  Winans SA, Luce Am, Hasbun R. Outpatient parenteral antimicrobial therapy for the treatment of methicillin-susceptible Staphylococcus aureus: a comparison of cefazolin and ceftriaxone. Infection 2013;41:769-774. https://www.ncbi.nlm.nih.gov/pubmed/23686435

3. Carr DR, Stiefel U, Bonomo RA, etal. A comparison of cefazolin versus ceftriaxone for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia in a tertiary care VA medical center. Open Forum Infectious Diseases, Volume 5, Issue 5, 1 may 2018, ofy089. https://academic.oup.com/ofid/article/5/5/ofy089/4999397

 

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My patient with foot osteomyelitis due to methicillin-sensitive Staphylococcus aureus (MSSA) is ready to go home on IV antibiotic therapy. Is daily ceftriaxone therapy an appropriate option?