Tag Archives: #antibioticstewardship

A Rash of Beta-Lactam Allergies, Part 3: The Solution

This post is the last in a three-part series covering the management of beta-lactam allergies. Part 1 explained the enormous impact that penicillin allergies have on patient outcomes, while Part 2 discussed the different types of allergic reactions and the potential (or lack thereof) for beta-lactam allergy cross reactivity. This last post will cover the methods used to assess beta-lactam allergies. Let’s jump right in!

There are a variety of strategies that can be used to assess a patient’s beta-lactam allergy, each having their own place in the allergy assessment algorithm. The following will be detailed in this post:

Detailed Patient Interview

Far and away the most important step in assessing a patient’s beta-lactam allergy is a detailed patient interview. An allergy evaluation is recommended by many of the top health organizations in the country, including the Center for Disease Control and Prevention (CDC), National Quality Forum, Infectious Diseases Society of America (IDSA), American Board of Internal Medicine (ABIM), and the American Academy of Allergy, Asthma & Immunology (AAAAI).1 Just a minute or two of questioning the patient can yield an entirely different story than the allergy history in the medical chart. Some common questions I bring up with patients include:

  • How many years ago did the reaction occur?
  • What type of reaction did you have?
  • Do you remember the details of the reaction? Did you have to go to the emergency room?
  • How long after starting the medication did the reaction occur?
  • How was the reaction managed?
  • What happened when the medication was stopped?
  • Have you tolerated other forms of penicillin since the reaction? Have you had Keflex (cephalexin), Augmentin (amoxicillin/clavulanate), or amoxicillin?
    • Using brand names to question patients in this situation is important, as many patients wouldn’t recognize the jumble of letters that is amoxicillin/clavulanate

You can develop your own arsenal of questions to ask patients, but the important part is to talk to them. No further strategies are needed if you can rule out the documented allergy just from a 90-second conversation.

Medication History

The other piece that is absolutely necessary before proceeding is looking through the patient’s medication history yourself. If a patient with a documented penicillin allergy received ceftriaxone without issue on an admission last year, you can go ahead and give full-dose ceftriaxone during this admission if needed. The patient interview and medication history review can rule out >50% of documented allergies in my experience. In these situations, you can skip directly to the last section of this post: allergy re-labelling.

Direct Challenge

In patients with a very low probability of allergic reaction, a beta-lactam antibiotic can usually be given without pause. Situations where you can rule out an allergy based on patient interview or medication history can be “challenged” directly. This means giving the full dose of the preferred antibiotic and monitoring for any adverse effects. Some institutions also give a direct oral amoxicillin challenge with 250-500 mg of amoxicillin once prior to the intended beta-lactam initiation. If the patient can tolerate amoxicillin, any penicillin antibiotic can be given in the future without fear of experiencing an IgE-mediated reaction.

Graded Challenge

When you are not able to completely rule out an allergic reaction, a graded challenge is often the next logical step in hospitalized patients. Graded challenges are used when there is a low probability of an allergic reaction, but there is still a degree of discomfort giving the entire dose up front. In general, 10% of the full dose is given, the patient is monitored closely for 30 minutes, and then the full dose is given if no issues arise. If the patient tolerates these doses, you can rule out immediate hypersensitivity reactions and document the tolerance in the medical record, which will be discussed at the end of this post.

Snippet of graded challenge guideline table from Brigham & Women’s Hospital

Desensitization

In patients who have confirmed or a high probability of severe IgE-mediated reactions to beta-lactams, but a beta-lactam is necessary for treatment, desensitization can be used. The desensitization procedure usually involves at least 12 doses of escalating concentrations of the required medication. This procedure requires incredibly close monitoring, which at most hospitals requires admission to the intensive care unit for administration. If a patient is able to tolerate desensitization, the patient must then begin regularly scheduled doses of the beta-lactam immediately upon the protocol completion. If doses are missed, the patient must be desensitized again. Desensitization does not rule out the allergy. The patient is still considered allergic to that agent, but can tolerate the medication for the course required in that instance.

Penicillin Skin Testing

Penicillin (PCN) skin testing has increased in popularity recently due to its relative ease of use and efficacy at ruling out IgE-mediated allergic reactions. In addition to rescue medications that should be handy just in case (diphenhydramine, methylprednisolone, and epinephrine) the skin test consists of 4 elements:

Initially, a percutaneous puncture test is done on the patient’s forearm with each of the elements and if tolerated, an intradermal test of each is also performed. The entire process generally takes around 45-60 minutes to complete and offers a negative predictive value for penicillin allergies of ~99%.2 Debate has surrounded the cost (both time and materials for the procedure), but multiple studies have now shown penicillin skin testing to be a cost-saving venture.2-5

Penicillin skin testing seems like a no-brainer, carrying the lowest risk of the procedures discussed thus far and its low overall cost for the health system. But in many institutions, it’s unclear who will perform the testing when allergy consultation is not available. In a 2015 survey of 736 infectious diseases providers, 57% responded saying that they do not have local options for skin testing.6 Does your institution?

The people of Twitter have spoken and it resulted in similar responses, with 62% of respondents not having penicillin skin testing available at their institution. Previous studies have reported on the successes of penicillin skin testing performed by allergists,7-9 & many more antimicrobial stewardship programs,10 infectious diseases fellows/physicians,11 nurses,12 and pharmacists.13,14 If you’ve read this far into the post, you likely are interested in allergy skin testing, so I’d implore you to own the process if your institution doesn’t already have skin testing available! ALK provides some excellent instructional videos on their website to guide you through the testing process. Pharmacists aren’t licensed to perform skin testing in all 50 states, but they are in many of them, which this 2019 article did an admirable job exploring.15

Allergy re-labelling

The last fundamental step in navigating beta-lactam allergies is updating the patient’s allergy label. With all of the previous interventions, the allergy documentation can be further described in the medical record, with desensitization being the only intervention that does not rule out IgE-mediated reactions altogether.

Green denotes interventions that can lead to allergy de-labelling. Red denotes the only intervention that should not lead to de-labelling

In an ideal world, inaccurate allergy labels should be removed from the medical record. Unfortunately, this practice often leads to redocumentation of the allergy at a later admission however.16 Many hospitals have integrated innovative ways to improve this repetitive cycle, as seen via providers’ personal experiences here, here, and here. For those without the tech support for any of this functionality though, the best thing to do is to document, document, document.

Summary

The majority of penicillin allergy labels do not belong to patients with true allergies and these unnecessary labels lead to worse patient outcomes. We should all strive for more accurate and detailed allergy documentation in our patients, which all starts with a patient interview. All of the interventions discussed above can be used to remove/relabel a beta-lactam allergy, with the exception of desensitization.

For those looking to learn more, I highly recommend a recent review published in JAMA that goes into further detail on penicillin allergies.17 Make sure to check out the supplementary material too, it has some super helpful resources, including a full allergy toolkit for penicillin skin testing and oral amoxicillin challenges!

Previous posts in this series:

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

A Rash of Beta-Lactam Allergies, Part 2: The Education

References

  1. Blumenthal KG, Shenoy ES, Wolfson AR, et al. Addressing inpatient beta-lactam allergies: a multihospital implementation. J Allergy Clin Immunol Pract. 2017;5:616-625
  2. Jones BM, Bland CM. Penicillin skin testing as an antimicrobial stewardship initiative. Am J Health-Syst Pharm. 2017;74:232-7
  3. Mattingly TJ, Meninger S, Heil EL. Penicillin skin testing in methicillin-sensitive staphylococcus aureus bacteremia: A cost-effectiveness analysis. PLoS One. 2019; 14(1):e0210271. doi: 10.1371/journal.pone.0210271
  4. Jones BM, Avramovski N, Concepcion AM, Crosby J, Bland CM. Clinical and Economic Outcomes of Penicillin Skin Testing as an Antimicrobial Stewardship Initiative in a Community Health System. Open Forum Infect Dis. 2019;6(4): ofz109. doi: 10.1093/ofid/ofz109
  5. Rimawi RH, Cook PP, Gooch M, et al. The impact of penicillin skin testing on clinical practice and antimicrobial stewardship. J Hosp Med. 2013;8(6):341-345
  6. Trubiano JA, Beekmann SE, Worth LJ, et al. Improving antimicrobial stewardship by antibiotic allergy delabeling: evaluation of knowledge, attitude, and practices throughout the Emerging Infections Network. Open Forum Infect Dis. 2016; 3(3):ofw153
  7. Blumenthal KG, Wickner PG, Hurwitz S, et al. Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship. J Allergy Clin Immunol. 2017;140:154-161
  8. Macy E, Shu YH. The Effect of Penicillin Allergy Testing on Future Health Care Utilization: A Matched Cohort Study. J Allergy Clin Immunol Pract. 2017;5(3):705-710
  9. Park M, Markus P, Matesic D, Li JT. Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy. Ann Allergy Asthma Immunol. 2006;97(5):681-687
  10. Leis JA, Palmay L, Ho G, et al. Point-of-Care β-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation. Clin Infect Dis. 2017;65(7):1059-1065
  11. Heil EL, Bork JT, Schmalzle SA, et al. Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin Testing Service. Open Forum Infect Dis. 2016;3(3):ofw155
  12. Macy E, Roppe LB, Schatz M. Routine Penicillin Skin Testing in Hospitalized Patients with a History of Penicillin Allergy. Perm J. 2004;8(3):20-24
  13. Chen JR, Tarver SA, Alvarez KS, Tran T, Khan DA. A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients. J Allergy Clin Immunol Pract. 2017;5(3):686-693
  14. Wall GC, Peters L, Leaders CB, Wille JA. Pharmacist-managed service providing penicillin allergy skin tests. Am J Health Syst Pharm. 2004;61(12):1271-1275
  15. Bland CM, Bookstaver PB, Griffith NC, et al. A practical guide for pharmacists to successfully implement penicillin allergy skin testing. Am J Health Syst Pharm. 2019;76(3):136-147
  16. Rimawi RH, Shah KB, Cook PP. Risk of redocumenting penicillin allergy in a cohort of patients with negative penicillin skin tests. J Hosp Med. 2013;8(11):615-618
  17. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and management of penicillin allergy: a review. JAMA. 2019;321(2):188-199

A Rash of Beta-Lactam Allergies, Part 2: The Education

This post is the second in a three-part series covering the management of beta-lactam allergies, all to be released on FOAMid over the last few months of 2019. Part 1 explained the enormous impact that penicillin allergies have on patient outcomes. Today we’ll discuss the different types of allergic reactions and the potential for beta-lactam allergy cross reactivity. Let’s jump right in!

Types of Allergic Reactions

The most common way of grouping immune-mediated hypersensitivity reactions is through the Gell & Coombs classification method.2 Using this scheme, there are four types of allergic reaction:

Type I reactions are IgE-mediated reactions and commonly referred to as immediate-type hypersensitivity reactions, since they occur minutes to hours post-exposure to an allergen. Type I reactions include anaphylaxis, angioedema, hypotension, flushing, wheezing, hives, and urticaria.

Both types II and III reactions are IgG-mediated.
Type II reactions, or cytotoxic reactions, include hemolytic anemia, thrombocytopenia, and neutropenia.
Type III reactions are immune complex reactions, and include serum sickness, glomerulonephritis, and arthritis.

Last, but certainly not least, are type IV reactions, which are T-cell mediated.
Type IV reactions are commonly referred to as delayed hypersensitivity reactions, despite Types II, III, and IV all technically being delayed in nature by days to weeks post-exposure to an allergen. A maculopapular rash, interstitial nephritis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are all considered type IV reactions.

Cross-Reactivity Risk

As discussed in the first post, many recorded antibiotic allergies are not true allergies. But when a patient does actually have a true penicillin allergy, what are the chances that the patient will have a similar reaction to other beta-lactams?

While we would generally avoid penicillins in this situation, other beta-lactams like cephalosporins and carbapenems could potentially be used. Previous studies of 10-25% cross-reactivity between cephalosporins and penicillins were primarily reported prior to 1982, when cephalosporin manufacturing processes were often contaminated with penicillin.12 Since then, the documented rate of cross-reactivity has dropped dramatically, shown in the table below.12

*not all cephalosporins are created equal (see comments below)

Cephalosporins

  • Cephalosporins that do not share a side chain with penicillin have a cross-reactivity risk of <2%
  • Cephalosporins that do share a similar side chain to penicillins (ex. cefoxitin and penicillin) have a cross-reactivity risk that is much higher

Side chain similarities don’t guarantee cross-reactivity, but they do increase the risk above the previously stated 2% threshold

But hold on, I thought the cause of beta-lactam allergies was the core beta-lactam ring that everyone remembers from their undergraduate years?

Penicillin molecule with the highlighted beta-lactam ring

Not so fast. While this plays a part, more recent literature has shown that the R1 and R2 side chains also play a role in the allergy potential of cephalosporins. I have adopted and updated a table from an excellent 2008 review paper by Daryl DePestel and colleagues below.3

In this table, the 3s, 6s, and 7s stand for similar R1 or R2 side chains, as described in the cephalosporin skeleton molecule, also seen below.

  • The R1 side chain is at the 7-position on the cephalosporin molecule and the 6-position on the penicillin molecule.
  • The R2 side chain is at the 3-position, which only differs among cephalosporins and not penicillins.

There are a couple of important clinical points to note from this table. Probably most important for clinical practice is that cefazolin does not share side chains with any other beta-lactam agents. This can have huge consequences on the use of cefazolin in practice, especially when it comes to surgical site prophylaxis and the treatment of methicillin-susceptible Staphylococcus aureus infections, both situations that could use cefazolin as first line therapy.

And while aztreonam is known as a beta-lactam with limited cross-reactivity due to dissimilar side chains, it does actually share a side chain with ceftazidime and the more recently approved ceftolozane (marketed in combination with tazobactam).

Aztreonam & Carbapenems

Speaking of aztreonam, we’ve spent the majority of this post discussing cephalosporin cross-reactivity risk. Now let’s spend a bit of time reviewing the other agents defined in the initial table in this post: carbapenems and aztreonam. Cross-reactivity between these agents and penicillins is minimal, as seen by a number of studies published by an Italian group headed by Antonino Romano and Francesco Gaeta.4,7,9

In their 2013 analysis, they found no patients had an allergic reaction to carbapenems, despite all 204 patients having a well-demonstrated T-cell-mediated hypersensitivity reaction to other beta-lactams (mostly penicillin).7

They went on to look at IgE-mediated hypersensitivity in their 2015 study, which found yet again no cases of hypersensitivity with either carbapenems OR aztreonam this time in a cohort of 212 patients with proven penicillin allergies.4

Then in 2016, they went back to T-cell-mediated hypersensitivity, examining 214 patients with proven reactions to penicillins and testing them against aztreonam. Once again, zero patients reacted to the aztreonam test doses or full dose.9

At this point, you may be questioning if the Italian group ever saw any reactions in their trial outcomes. The last study presented above that showed no reactions with aztreonam though tested more than just aztreonam. They also looked at cephalosporins and saw an 18.7% chance of positive skin testing with aminocephalosporins (cephalexin, cefadroxil, cefaclor).9 If you refer back to the previous cross-reactivity table, you can see that these three agents share a side chain with ampicillin and amoxicillin.

So while side chains play a key role in determining cross-reactivity among cephalosporins, we can be fairly confident that carbapenems and aztreonam are safe to administer in the majority of situations, especially when a non-severe penicillin allergy is documented. This will be covered in more detail in the next (and final) installment of “A Rash of Beta-Lactam Allergies,” coming to you soon!

Other posts in this series:

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

A Rash of Beta-Lactam Allergies, Part 3: The Solution

References

  1. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic Allergy. Lancet. 2019; 393(10167):183-198
  2. Coombs P, Gell PG. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: G RR, P.G.H Gell, eds. Clinical aspects of immunology. Oxford, UK: Oxford University Press, 1968; 575-596
  3. Frumin J, Gallagher JC. Allergic cross-sensitivity between penicillin, carbapenem, and monobactam antibiotics: what are the chances? Ann Pharmacother. 2009; 43:304-315
  4. Gaeta F, Valluzzi RL, Alonzi C, Maggioletti M, Caruso C, Romano A. Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2015; 135:972-976
  5. Joint Task Force on Practice Parameters; American Academy, American College, & Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010; 105:259-273
  6. Legendre DP, Muzny CA, Marshall GD, Swiatlo E. Antibiotic hypersensitivity reactions and approaches to desensitization. Clin Infect Dis. 2014; 58(8):1140-1148
  7. Romano A, Gaeta F, Valluzzi RL, et al. Absence of cross-reactivity to carbapenems in patients with delayed hypersensitivity to penicillins. Allergy. 2013; 68:1618-1621
  8. Romano A, Gaeta F, Arribas Poves MF, Valluzzi RL. Cross-reactivity among beta-lactams. Curr Allergy Asthma Rep. 2016; 16:24
  9. Romano A, Gaeta F, Valluzzi RL, Maggioletti M, Caruso C, Quaratino D. Cross-reactivity and tolerability of aztreonam and cephalosporins in subjects with a T cell-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2016; 138:179-186
  10. Romano A, Valluzzi RL, Caruso C, Maggioletti M, Quaratino D, Gaeta F. Cross-reactivity and tolerability of cephalosporins in patients with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol Pract. 2018; 6(5):1662-1672
  11. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and management of penicillin allergy: a review. JAMA. 2019; 321(2):188-199
  12. Trubiano JA, Stone CA, Grayson ML, et al. The 3 Cs of antibiotic allergy-classification, cross-reactivity, and collaboration. J Allergy Clin Immunol Pract. 2017; 5(6):1532-1542

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”!

Other posts in this series:

A Rash of Beta-Lactam Allergies, Part 2: The Education

A Rash of Beta-Lactam Allergies, Part 3: The Solution

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

Prevention of Clostridium difficile infection

Often, the focus of medical education is on clinical diagnosis and management of disease. But what about prevention? Prevention is key. Here are some ways for both the patient and healthcare provider to prevent further infections:

Prevent C.diff infographic

 

  1. Reduce transmission as much as possible
    1. Wash hands with soap and water after leaving the room of a patient with active C. difficile infection (CDI) OR use an alcohol-based hand sanitizer if a sink is not available
    2. Advocate healthcare facilities to:
      • place sinks nearby patient rooms
      • consider sink placement in the future construction of healthcare facilities
    3. Educate your patients and those who live with them to:
      • wash their hands well after using the toilet
      • have infected individuals use separate toilets and toilet accessories during treatment, if possible
  1. Avoid unnecessary antibiotic use
    • Avoid prescribing an antibiotic if low likelihood of bacterial infection
    • Narrow broad-spectrum antibiotics as soon as possible
    • Discontinue antibiotics as soon as possible
  2. Consider prophylactic PO vancomycin for patients with history of recurrent C. difficile infection
    • A retrospective review demonstrated that administration of PO vancomycin 125mg twice a day was associated with a lower incidence of recurrent C. difficile infection (4.2% vs. 26.6%, p<0.001)3 
  1. Educate yourself on the risks and benefits of probiotic use and be able to relay that information to your patients if they ask.
    • Some studies show no reduction in incidence of C. difficile infection with probiotic use6,7
    • Other studies (including a Cochrane review) show significant reduction in C. difficile infection incidence with probiotic use8,9,10,11
    • Studies have demonstrated that probiotics are more likely to reduce C. difficile infection incidence:
      • in patients with a baseline risk of C. difficile infection > 5%8,9
      • when probiotics are administered at higher doses10
      • when the probiotic consists of multiple strains10
      • when probiotics were administered within 2 days of antibiotic initiation11
    • This is the IDSA Clinical Practice Guidelines for C. difficile infection statement on probiotics:
      “There are insufficient data at this time to recommend administration of probiotics for primary prevention of CDI outside of clinical trials (no recommendation).”
      The guidelines cite the bias towards probiotics in many trials that enrolled mostly patients at very high risk of C.difficile infection and the potential for probiotics to cause harm by introducing new infections to hospitalized patients.

 Any prevention strategies I didn’t mention? What do you think is the most effective prevention strategy? I would love to hear your thoughts!

 

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.
  2. Jorgensen JH, Pfaller MA, Carroll KC, et al. Manual of Clinical Microbiology, Eleventh Edition.
  3. Van Hise NW, Bryant AM, Hennessey EK, et al. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016; 63(5):651-653.
  4. 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.
  5. Davidson LE and Hibberd PL. Clostridioides difficile and probiotics. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-and-probiotics]. Accessed Nov 13, 2018.
  6. Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013; 382(9900): 1249-57.
  7. Ehrhardt S, Guo N, Hinz R, Schoppen S, May J, Reiser M, et al. Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial. Open Forum Infect Dis. 2016; 3(1):ofw011.
  8. Goldenberg JZ, Yap C, Lytvyn L, Lo CK, Beardsley J, Mertz D, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017; 12:CD006095.
  9. Johnston BC, Lytvyn L, Lo CK, Allen SJ, Wang D, Szajewska H, et al. Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants. Infect Control Hosp Epidemiol. 2018; 39(7): 771-781.
  10. Johnston BC, Ma SSY, Goldenberg JZ, Thorlung K, Vandvik PO, Loeb M, et al. Probiotics for the Prevention of Clostridium difficile-Associated Diarrhea. Ann of Intern Med. 2012; 157:878-888
  11. Shen NT, Maw A, Tmanova LL, Pino A, Ancy K, Crawford CV, et al. Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficle Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology. 2017; 152(8): 1889-1900.

 

 

 

 

IDWeek 2018 Review

Dolores Park SF
Mission Dolores Park in San Francisco – photo courtesy of Ahmed Abdul Azim @triplea87

 

During the first week of October, the Infectious Diseases Society of America (IDSA) hosted its’ annual Infectious Diseases conference (IDWeek) in San Francisco, California.

There are a variety of reviews of the conference on the internet (the most famous being the Mini Really Rapid Review by Dr. Paul Sax) but I want to highlight the studies that are pertinent to physicians in other specialties outside of ID.

 

  • Two major studies highlighted the ongoing pressures and scope for over-prescription of antibiotics and need for antimicrobial stewardship
    In one study, 66.1% of patients were prescribed antibiotics for respiratory tract infections and antibiotic prescribing was associated with higher patient satisfaction. Given that most respiratory tract infections are viral, 66% is a lot!
    Another study showed that 20% of antibiotics are prescribed without an in-person visit. Of all the 509,534 antibiotic prescriptions, 46% were not associated with an infection-related diagnosis. This highlights the need for better provider and patient education in antibiotic stewardship.

 

 

 

 

 

 

 

 

 

 

  • IV drug use may be an independent risk factor for candidemia.
    This study showed an increasing incidence of candidemia and higher numbers of patients with candidemia who are persons who inject drugs without other risk factors. Something to keep in mind when you see patients who inject drugs in your hospital.

 

And for those of you in San Francisco, watch out for these microbes:

 

It’s impossible to cover everything so if you attended IDWeek and have other studies to suggest to everyone, let us know in the comments.

CAP vs. HCAP vs. HAP vs. VAP

This post is written by a guest writer, Jeff Pearson, PharmD. 

In 2016, the Infectious Diseases Society of America (IDSA) published updated guidelines for the treatment of hospital-acquired pneumonia (HAP) & ventilator-associated pneumonia (VAP).

The plan was to release new community-acquired pneumonia (CAP) guidelines shortly thereafter.

Those CAP guidelines have now been pushed back to be tentatively published in summer 2018.

This post is meant to cover some common misconceptions about the treatment of pneumonia and clinical pearls while we patiently await the release of the new guidelines.

Let’s start with the basics:

HCAP & CAP – those presenting to the hospital with pneumonia
HAP & VAP – those that developed pneumonia >48 hours after admission to the hospital or mechanical ventilation, respectively.

CAP vs HCAP vs HAP vs VAP

But I thought the term HCAP was gone…

While the 2016 guidelines no longer address HCAP, HCAP as an entity has not disappeared (despite what some may tell you). It will likely be discussed in the as-of-yet unreleased CAP guidelines. But in the meantime, feel free to use the algorithm presented above for guidance.

Previous guidelines from 2005 grouped HCAP in with HAP and VAP in terms of treatment. But since then, it’s been determined that not all HCAP patients require MRSA and Pseudomonas coverage. Many can be treated as typical CAP patients.

High-risk HCAP patients =

  • multiple risk factors for multi-drug resistant organisms (see green-box above)
  • require ICU admission to justify broad spectrum antibiotic treatment.

Treatment:

CAP/low risk HCAP
—–NO MRSA or Pseudomonas coverage
—–YES atypical pneumonia pathogens coverage (i.e. mycoplasma, legionella, chlamydia spp.)
Ex. Levofloxacin; ceftriaxone + azithromycin*

High-risk HCAP
—–YES MRSA and Pseudomonas coverage
—–YES atypical pneumonia pathogens coverage (i.e. mycoplasma, legionella, chlamydia spp.)
Ex. Vancomycin + cefepime + azithromycin*

HAP
—–YES MRSA and Pseudomonas coverage
—–Consider double pseudomonal coverage if patient is hemodynamically unstable
—–NO atypical pneumonia pathogen coverage
Ex. Vancomycin + cefepime*

VAP
—–YES MRSA and Pseudomonas coverage
—–Consider double pseudomonal coverage if patient is hemodynamically unstable
—–NO atypical pneumonia pathogen coverage
Ex. Vancomycin + cefepime + tobramycin*

*These are example regimens. Please reference your own institution’s pneumonia guidelines for additional information.

 

Duration of Treatment = 7 days!!!

* This can likely be even shorter in cases of CAP.
** From the IDSA: “There exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters.” 2

TAKE-HOME POINTS:

  • HCAP is still an entity – but it has been separated from HAP
  • CAP and HCAP – pneumonia <48 hours into a hospital stay
    HAP and VAP – pneumonia >48 hours into a hospital stay
  • CAP and low risk HCAPNO need for MRSA and Pseudomonas coverage
    High risk HCAP, HAP, and VAPDO need MRSA and Pseudomonas coverage
  • Duration of treatment = 7 days

 

References:

  1. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44:S27-S72
  2. 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
  3. Dinh A, Ropers J, Davido B, et al. Effectiveness of three days of beta-lactam antibiotics for hospitalized community-acquired pneumonia: a randomized non-inferiority double-blind trial [abstract]. ECCMID Madrid, Spain, April 22, 2018.

Guest author: Jeff Pearson is currently a PGY-2 infectious diseases pharmacy resident at Beth Israel Deaconess Medical Center in Boston, Massachusetts. He also serves as an adjunct faculty member at MCPHS University, lecturing and facilitating in various courses. He received his Doctor of Pharmacy from Northeastern University in 2014. His main area of interest is antimicrobial stewardship and he will be a senior pharmacist in infectious diseases at Brigham and Women’s Hospital after completing his residency year in August 2018.

 

Peer-reviewed by Milana Bogorodskaya, MD