Tag Archives: #antibiotics

A Rash of Beta-Lactam Allergies, Part 1: The Problem

This post marks part 1 of a 3-part series covering the management of beta-lactam allergies, all to be released on FOAMid over the next couple of months.

  1.  This post, “The Problem,” provides background and the impact of a reported beta-lactam allergy
  2. “The Education” will delve into the types of allergic reactions, as well as cross reactivity potential among beta-lactam antibiotics
  3. “The Solution” will then explore how to best assess a patient’s documented allergy

With that, let’s jump right in!

Overview

A whopping 10% of the general population has a reported penicillin (PCN) allergy. But only 1-10% of these people have a true allergy when tested. This leaves us with about 0.1-1% of the general population with a true penicillin allergy.

Why is there such a discrepancy between reported allergies and true allergies? A lot of it comes from inaccurate allergy histories, like the patient with GI upset as a child, but the allergy listed as an “unknown reaction.” Or better yet, the patient whose mother had an allergy and thus everyone in the family has been given that scarlet letter in their medical record.

Another important and lesser known reason for the allergy discrepancy is that 78% of patients with immediate hypersensitivity to penicillin see their penicillin allergy fade after 10 years (from this 1981 study). So those adult patients with childhood reactions? The odds are that they aren’t still allergic decades later.

Why should we care?

When it comes to infectious diseases, beta-lactam antibiotics are often our first- and second-line options for treatment. A documented penicillin allergy can essentially knock a practitioner down to third-line treatment in some situations. In just highlighting a few common infections and organisms, look at how often beta-lactams are brought up:

When a patient has a documented penicillin allergy, studies have proven that beta-lactam usage decreases while non-beta-lactam usage increases (Lee 2000, as well as half of the citations provided at the end of this post). And when beta-lactams are avoided, patients tend to do worse.

Impact on Patient Outcomes

The impact of a penicillin allergy is real and detrimental to our patients. Rather than bore you with paragraphs upon paragraphs detailing the many studies looking into this fact, here are some take-home points hyperlinked to the primary literature supporting the claims:

Penicillin allergy patients:

There is clear evidence that reported beta-lactam allergies pose a problem on the path to prescribing optimal treatment in infectious diseases. We can combat the issue however through education and assessment techniques.

More to come in parts 2 and 3 of “A Rash of Beta-Lactam Allergies”!

by Jeff Pearson

References

  1. Al-Hasan MN, Acker EC, Kohn JE, Bookstaver PB, Justo JA. Impact of penicillin allergy on empirical carbapenem use in gram-negative bloodstream infections: an antimicrobial stewardship opportunity. Pharmacotherapy. 2017; 38(1):42-50
  2. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015; 132:1435-1486
  3. Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018; 361:k2400
  4. Blumenthal KG, Ryan EE, Li Y, Lee H, Kuhlen JL, Shenoy ES. The impact of a reported penicillin allergy on surgical site infection risk. Clin Infect Dis. 2018; 66(3):329-336
  5. Borch JE, Andersen KE, Bindslev-Jensen C. The prevalence of suspected and challenge-verified penicillin allergy in a university hospital population. Basic Clin Pharmacol Toxicol. 2006; 98:357-362
  6. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect. 2013;14(1):73-156
  7. Charneski L, Deshpande G, Smith SW. Impact of an antimicrobial allergy label in the medical record on clinical outcomes in hospitalized patients. Pharmacotherapy. 2011; 31(8):742-747
  8. Conway EL, Lin K, Sellick JA, et al. Impact of penicillin allergy on time to first dose of antimicrobial therapy and clinical outcomes. Clin Ther. 2017; 39(11):2276-2283
  9. Huang KHG, Cluzet V, Hamilton K, Fadugba O. The impact of reported beta-lactam allergy in hospitalized patients with hematologic malignancies requiring antibiotics. Clin Infect Dis. 2018; 67(1):27-33
  10. Jeffres MN, Narayanan PP, Shuster JE, Schramm GE. Consequences of avoiding β-lactams in patients with β-lactam allergies. J Allergy Clin Immunol. 2016; 137(4):1148-1153
  11. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016; 63(5):e61-e111
  12. Lee CE, Zembower TR, Fotis MA, et al. The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance. Arch Intern Med. 2000;160(18):2819-2822
  13. Macy E, Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Pract. 2013; 1:258-263
  14. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: A cohort study. J Allergy Clin Immunol. 2014; 133(3):790-796
  15. Solensky R. The time for penicillin skin testing is here. J Allergy Clin Immunol Pract. 2013; 1(3):264-265
  16. Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014; 59(2):e10-e52
  17. Sullivan TJ, Wedner HJ, Shatz GS, Yecies LD, Parker CW. Skin testing to detect penicillin allergy. J Allergy Clin Immunol. 1981; 66(3):171-180
  18. Trubiano JA, Chen C, Cheng AC, et al. Antimicrobial allergy ‘labels’ drive inappropriate antimicrobial prescribing: lessons for stewardship. J Antimicrob Chemother. 2016; 71:1715-1722
  19. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267-1284
  20. van Dijk SM, Gardarsdottir H, Wassenberg MW, Oosterheert JJ, de Groot MC, Rockmann H. The high impact of penicillin allergy registration in hospitalized patients. J Allergy Clin Immunol Pract. 2016; 4:926-931

Clostridium difficile

In light of the recently published IDSA guidelines on C. difficile, I thought I would write up a summary of the guidelines as well as provide some of the background microbiology of the organism for review.

Structure

  • obligate anaerobes
  • gram-positive bacilli
    – form spores (= dormant, non-reproductive structure that the bacteria can reduce itself to in order to survive for extended periods of time in extreme conditions)
  • produce toxins (toxin A and toxin B) that cause disease

 

clostridium-difficile gram stain

Environment

  • animal and human feces
  • soil
  • sewage

 

Mechanism of pathogenicity

*Not all strains of C. difficile are pathogenic – only the ones who produce toxins can cause C. difficile disease

Pathogenesis:

Transmission occurs with ingestion of spores via the fecal-oral route ⇒ spores activate in the colon to replicating bacteria ⇒ bacteria release toxins ⇒ toxins cause breakdown of the colon cells’ cytoskeleton framework ⇒ apoptosis ⇒ breakdown of the mucosal wall ⇒ DIARRHEA!

 

Risk factors for acquiring C. difficile:

  1. ANTIBIOTIC EXPOSURE
  2. Exposure to healthcare facilities
  3. Age and immunosuppression
  4. ?Gastric acid suppression (use of proton pump inhibitors or H2 receptor blockers)
    — the evidence-based-medicine jury is still out on this one

 

Clinical features

  • symptoms can develop during antibiotic treatment or up to 6 weeks after the course of antibiotics has been finished
  • patients can also become infected even without exposure to antibiotics (both in the healthcare setting but also in the community setting)
  • carrier state = a patient who is colonized with C. difficile but is currently asymptomatic

1.Symptoms and physical exam signs:

  • Non-bloody, WATERY DIARRHEA (≥ 3 loose stools in 24 hours)
    *occasionally patients can develop ileus with severe infection which will not result in diarrhea but rather lack of bowel movements
  • Abdominal pain/cramping
  • Fever and chills
  • Abdominal distention/tenderness
  • Nausea/anorexia

2.Laboratory findings:

  • High white blood count (occasionally precedes the diarrhea by 1-2 days)
  • Elevated creatinine
  • Elevated lactate and low albumin (in fulminant cases)

 

Pseudomembranous colitis = inflammation of the colon causing elevated white and yellow-colored plaques to form and coalesce together to create a pseudomembrane on the colon wall that can be seen by colonoscopy.

 

Diagnostics

  1. When to test: when patient has new onset, ≥ 3 unformed stools that cannot be explained by another cause (i.e. laxative use)
  2. Options for testing:

* C. difficile can be grown in culture, but anaerobes take a while to grow and it would not provide an answer as to whether the strain is toxigenic (i.e. produces toxin) or not, so it is not commonly used for clinical diagnostic purposes.

What it is Advantages Disadvantages
Toxin EIA assay Antibody assay that detect toxins High specificity (>84%) Low sensitivity (31-99%)
GDH assay Detects GDH (an enzyme produced by C. difficile) High NPV (>99%)

Quick turn-around

Cannot distinguish toxigenic vs. non-toxigenic C. difficile strains
NAAT/PCR PCR method that detects toxin production gene High NPV (>99%)

Quick turn-around

Poor specificity and PPV

*Changes depending on whom specimens are collected on (low suspicion vs. high suspicion)

EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NPV, negative predictive value; PPV, positive predictive value; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction.

Many healthcare facilities are currently doing only PCR testing. It’s highly sensitive and the results return quickly (usually within 24 hours).

The problem: this practice is yielding a lot of false positives (patients who are carriers but do not truly have an active infection) which ⇒ over-treatment ⇒ patient discomfort, potential side effects, infection control consequences for the hospital, and extra costs.

Why: This is thought to be due to the fact that a lot of tests are sent inappropriately (on patients that have diarrhea but no other evidence of infection such as leukocytosis, AKI, abdominal pain, fever, etc.)

Solution (as proposed by IDSA guidelines):

  1. A multiple step algorithm:
  • GDH assay + EIA assay
  • GDH assay + EIA assay with NAAT as a tiebreaker
  • NAAT + EIA assay

                  OR

  1. We can agree to be more mindful of when we send the test (when the pre-test probability is high) and continue to use the NAAT/PCR method alone.

Bottom line: Many hospitals are switching over to the two-step testing method for multiple reasons:

  • behavior change is difficult to implement and sustain
  • provides more accurate incidence of nosocomial-acquired infections in the hospital

WHEN YOU THINK OF SENDING A C. DIFFICILE TEST, ask yourself:

  1. Does this patient have an unexplained fever, leukocytosis, or new abdominal pain/distention, in addition to the diarrhea (or in presence of ileus)?
    if yes ⇒ send the test
  1. If not, is there another explanation for the diarrhea?
    (i.e. laxatives, new medications (especially antibiotics), part of already known illness, etc.)
    if yes ⇒ consider removing the potential cause (if possible) and re-evaluate or monitor for worsening symptoms
    if not ⇒ send the test

 

Treatment

The IDSA has a really great table to reference when choosing treatment options for your C. difficile infected patient.

***PO Metronidazole is no longer the 1st-line agent for C. diff infection treatment***

C.diff treatment chart

                                                                                                            McDonald et al. CID 2018

 

Recurrence

Recurrence of C. difficile infection = reappearance of symptoms within 2-8 weeks after completion of therapy

  • up to 25% of patients will experience a recurrence
  • once patient had one recurrence, they are at higher risk for future recurrences

 

TAKE-HOME POINTS:

  • The MAJOR risk factor for C. difficile infection is ANTIBIOTIC EXPOSURE
    ⇒ DO NOT give antibiotics to those who do not truly need them
  • Symptoms/signs include watery diarrhea, abdominal cramping/pain, and elevated WBC and creatinine
  • C. difficile infection CAN cause ileus (i.e. no diarrhea)
  • Only send test when you have a high pre-test probability to avoid false positives
  • Metronidazole is NO LONGER recommended for treatment of C. difficile

 

Got questions? Disagree? Leave your comments below!

 

References

  1. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018. 66(7):1-48. [PMID: 29562266]
  2. Jorgensen JH, Pfaller MA, Carroll KC, et al. Manual of Clinical Microbiology, Eleventh Edition.
  3. Lamont JT. (2018). Clostridium difficile infection in adults: Epidemiology, microbiology, and pathophysiology. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-epidemiology-microbiology-and-pathophysiology]. Accessed May 25, 2018.
  4. Lamont JT, Kelly CP, and Bakken JS. Clostridium difficile infection in adults: Clinical manifestations and diagnosis. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-clinical-manifestations-and-diagnosis]. Accessed May 25, 2018.
  5. Kelly CP, Lamont JT, and Bakken JS. Clostridium difficile infection in adults: Treatment and prevention. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-treatment-and-prevention]. Accessed May 25, 2018.