What’s the connection between lemon juice and disseminated candidiasis in my patient with illicit IV drug use?

Lemon juice is often used by IV drug users to help dissolve poorly water soluble street drugs, such as brown heroin or crack-cocaine, and may serve as a vehicle for Candida albicans infection. 1-3

Contamination of lemon juice (either from wild lemons or from the plastic containers) is thought to occur from either the skin and/or oropharynx of the user.1  Other fruit juices such as orange juice as well as raspberry syrup have been implicated as a source of disseminated candidiasis in IV drug users.4

Experimental inoculation of lemons with small numbers of C. albicans has demonstrated rapid growth of the organism at room temperature resulting in inadvertent injection of a large inoculum size. 2 Once inoculated directly into the blood stream, C. albicans disseminates and can present in many ways, including skin lesions, ocular lesions/endophthalmitis, and osteoarticular infections (eg, costochondral, hip joint, and vertebral infections).1  

So it is advisable to not only ask about what recreational drug is being injected but also what it is injected with!

Bonus Pearl: Did you know that although lemon juice is an excellent growth medium for C. albicans, it has bactericidal properties against Staphylococcus aureus and Pseudomonas aeruginosa? 1

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References

  1. Bisbe J, Miro JM, Latorre X, et al. Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin Infect Dis 1992;15:910-23. https://www.ncbi.nlm.nih.gov/pubmed/1457662
  2. Newton-John HGF, Wise K, Looke DFM. Role of the lemon in disseminated candidiasis of heroin abusers. Med j Aust 1984;140:780-81. https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1984.tb132597.x?sid=nlm%3Apubmed
  3. Shankland GS, Richardson MD. Source of infection in candida endophthalmitis in drug addicts. Br J Ophthalmol 1986;292:1106-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954783/pdf/702.pdf
  4. Scheidegger C, Pietrzak J, Frei R. Methadone diluted with contaminated orange juice or raspberry syrup as a potential source of disseminated candidiasis in drug abusers. Eur J Clin Microbiol Infect Dis 1993;12:229-31. https://link.springer.com/article/10.1007/BF01967124
What’s the connection between lemon juice and disseminated candidiasis in my patient with illicit IV drug use?

Do most patients with mycotic aneurysms have endocarditis?

No! In fact, the great majority of patients who develop mycotic aneurysm (MAs) in the postantibiotic era have no evidence of endocarditis1-3.

MAs are thought to be related to microbial arteritis due to blood stream infection of any source with implantation of circulating pathogen (usually bacterial) in atherosclerotic, diseased, or traumatized aortic intima. Plus, MAs may develop due to an adjacent infectious process (eg, vertebral osteomyelitis), either through direct extension or via lymphatic vessels, pathogen seeding of vasa vasorum, or infection of a pre-existing aneurysm1,2.  All these factors may occur in the absence of endocarditis.

Many of your patients may be at risk of MA such as those with advanced age or history of diagnostic or therapeutic arterial catheterization, illicit intravascular drug use, hemodialysis and depressed host immunity1-3..  Staphylococcus aureus, Salmonella sp, S. epidermidis and Streptococcus sp are common culprits in descending order1-3.

So think of MA in your patient with recent blood stream infection,  particularly due to S. aureus or Salmonella sp, in the setting of persistent signs of infection  with or without evidence of endocarditis.

Final Fun Fact: Did you know that the term “mycotic aneurysm” is a misnomer, having been first introduced by Sir William Osler to describe aneurysms of the aortic arch in a patient with (you guessed it) bacterial not fungal endocarditis?

References:

  1. Gomes MN, Choyke PL, Wallace RB. Infected aortic aneurysms: A changing entity. Ann Surg 1992;215:435-42. https://www.ncbi.nlm.nih.gov/pubmed/1616380
  2. Muller BT, Wegener OR, Grabitz K, et al. Mycotic aneurysms of the thoracic and abdominal aorta and iliac arteries: Experience with anatomic and extra-anatomic repair in 33 cases. J Vasc Surg 2001;33:106-13. https://www.ncbi.nlm.nih.gov/pubmed/11137930
  3. Mukherjee JT, Nautiyal A, Labib SB. Mycotic aneurysms of the ascending aorta. Tex Heart Inst J 2012;39:692-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461658/
Do most patients with mycotic aneurysms have endocarditis?

My patient has a sacral decubitus ulcer that can be probed to the bone. Should I assume she has osteomyelitis?

When dealing with pressure sores, there is no definitive way of making a diagnosis of osteomyelitis short of a biopsy of the involved bone1.  In fact, only about a third of stage IV pressure ulcers (those extending to the bone) may be associated with osteomyelitis2. In a study of pressure sores related to spinal cord injury or cerebrovascular accident, the clinical judgement of physicians with respect to the presence of osteomyelitis was accurate in only 56% of patients.  Only 3 of 21 patients with exposed bone had a diagnosis of osteomyelitis confirmed on biopsy3.

The “Probe to the Bone” bedside procedure has been studied primarily in diabetic foot infections with a recent systematic review reporting pooled sensitivity and specificity of 0.87 (95% confidence interval [CI], .75-.93) and 0.83 (95% CI, .65-.93), respectively4. Its performance in non-diabetic patients or those without a foot infection needs further study.

So in our patient, we should not assume a diagnosis of osteomyelitis; a bone biopsy is necessary for a definitive diagnosis.

References

  1. Larson DL, Gilstrap J, Simonelic K, et al. Is there a simple, definitive, and cost-effective way to diagnose osteomyelitis in the pressure ulcer patient? Plast Reconstr Surg 2011; 127:67.  https://www.ncbi.nlm.nih.gov/pubmed/21285771
  2. Bodavula P, Liang SY, Wu J et al. Pressure ulcer-related pelvic osteomyelitis: a neglected disease? Open Forum Infect Dis 2015. DOI:10.1093/ofid/ofv112. https://www.ncbi.nlm.nih.gov/pubmed/26322317
  3. Darouiche RO, Landon GC, Klima M et al. Osteomyelitis associated with pressure sores. Arch Intern Med 1994;154:753-58. https://www.ncbi.nlm.nih.gov/pubmed/8147679
  4. Lam K, van Asten SA, Nguyen T, et al. Diagnostic accuracy of probe to bone to detect osteomyelitis in the diabetic foot: a systematic review. Clin Infect Dis 2016;63:944-8. https://www.ncbi.nlm.nih.gov/pubmed/27369321
My patient has a sacral decubitus ulcer that can be probed to the bone. Should I assume she has osteomyelitis?

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?