Postinfection Complications: Vigilance at the Counter

Vigilant pharmacists can help patients identify postinfection complications.

At this time of year, a large number of patients enter the pharmacy with prescriptions for antibiotics and symptom control medications in hand. These treatments can cure bacterial infections and ameliorate symptoms related to a viral or bacterial infection, but in rare cases, autoimmune or systemic syndromes develop later. Vigilance at the counter can help patients identify postinfection complications (eg, poststreptococcal complications, shingles, antibiotic-induced diarrhea) early so they can seek appropriate care.

Streptococcal Infection

Streptococcal infection of the skin (impetigo or scarlet fever) or of the throat (strep throat) can cause several complications, including rheumatic fever, glomerulonephritis, or a syndrome now dubbed PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections). These conditions are rare, but they are a good reason to say to patients, “Take this antibiotic as prescribed, and be sure to take it all.”

In rare cases, untreated strep infection may progress to rheumatic fever, potentially involving the heart, joints, brain, or skin. Rheumatic carditis, the most severe manifestation, causes chronic progressive valve deformation and, subsequently, heart murmur. Some patients develop Sydenham chorea (formerly called St. Vidus dance; characterized by uncontrollable, jerking twitches that disappear during sleep) alone or with carditis, or polymigrating arthritis.¹ Patients who develop rheumatic fever generally need a 4-pronged approach (Table 1^2-4).^2,3

Physicians first recognized acute glomerulonephritis associated with streptococcal infection in the 18th century. Scarlet fever was epidemic, and recovering patients were at high risk for hematuria, proteinuria, red blood cell casts in the urine, edema, and hypertension with or without oliguria. The link between hemolytic streptococci and acute glomerulonephritis was solidified in the 1940s.^5,6 After infection with group A beta-hemolytic streptococci, postinfectious glomerulonephritis (PIGN) may occur and is a reactive immunologic process. Classic PIGN occurs in childhood, but elderly patients with multiple comorbidities are also at risk, and this diagnosis is often overlooked in older patients. However, treatment of the strep infection may not prevent glomerulonephritis. The condition is relatively rare, occurs predominately in males, and may resolve without treatment, but some complications may require treatment. Patients with these symptoms should be referred to a physician.³

The term PANDAS encompasses certain disorders (eg, obsessive compulsive disorder [OCD], Tourette’s syndrome) that worsen after group A streptococcal infections. Unlike children who have childhood OCD (the symptoms of which develop slowly over time), children with PANDAS usually develop symptoms quickly. They also present with urinary urgency, hyperactivity, impulsivity, choreiform movements, and deteriorating handwriting. These symptoms reflect disrupted basal ganglia functions.

Treatments for PANDAS are identical to those used for OCD or tic disorders: cognitive behavioral therapy and OCD medications. Retreatment with penicillin is not helpful because PANDAS appears to be caused by antibodies to the strep infection, not to the bacteria. Children with severe PANDAS may benefit from treatment with plasmapheresis and immunoglobulin, but these treatments are associated with significant adverse effects.^4,7 Refer these patients to a physician.

Zoster Infection

Chickenpox infection (varicella) was an expected occurrence among school children until a safe, effective vaccine became available and its uptake became widespread. Varicella lingers after infection and is no problem until infected individuals become approximately 60 years of age. Up to 40% of people 50 years and older develop shingles and/or postherpetic neuralgia (Table 2^8,9).⁸

Shingles can be prevented: a live, attenuated vaccine reduces the likelihood of developing the disease by 50% and reduces postherpetic neuralgia by 67%, lessening its symptoms if it occurs.10 Uptake of this vaccine is lower than ideal: in 2011, approximately 22% of eligible seniors had been vaccinated,¹¹ creating an opportunity for immunizing pharmacists to promote this intervention.

If shingles (herpes zoster) is caught early (within 72 hours of rash or initial burning pain), aggressive treatment with antivirals (acyclovir, famciclovir, valacyclovir [a prodrug that is metabolized to acyclovir]) may reduce acute pain and hasten healing.¹² Some guidelines address neuropathic pain and recommend starting with a tricyclic antidepressant, gabapentin, or pregabalin. Some patients require treatment with opioids.⁸ Although these treatments may reduce pain, the magnitude of the decrease is usually only 20% to 40%.¹³ Because many patients with herpes zoster infection are older, have comorbid conditions, and take several medications, treatment can be challenging.

Clostridium Difficile Infection

Frequent and prolonged use of antibiotics may disturb the colon’s normal bacterial flora and allow Clostridium difficile colonization. Subsequent toxin release inflames and damages the mucosal wall, causing C difficile—associated diarrhea (CDAD). Here, the problem is antibiotic misuse. The Centers for Disease Control and Prevention reports that a 30% reduction in the use of broadspectrum antibiotics would reduce the incidence of C difficile infections by 26%.¹⁴ CDAD’s symptoms—watery diarrhea, cramping, pain, anorexia, and fatigue—can be life-threatening. Treatment generally involves consideration of the infection severity, local epidemiology, and the infecting C difficile strain. Cephalosporins, clindamycin, and, in severe cases, vancomycin are the drugs of choice.^15,16

Endnote

Consultation between pharmacists and patients can resolve medication problems and lead to reasonable self-care plans or referral. In particular, pharmacists need to stress adherence when patients present with strep infections, advise against rampant antibiotic use, and promote immunization. Pharmacists have a key role in preventing postinfection complications and in recognizing that they could be developing, based on patient questions. Often, patients stop taking their antibiotics when they feel better, so patients or parents should be strongly advised to take all prescribed doses. It’s also important to know whether patients’ insurers cover immunizations, as cost can be a significant barrier.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References

1. Stollerman GH. Rheumatic fever. Lancet. 1997;349:935-942.

2. Walker KG, de Vries PJ, Stein DJ, Wilmshurst JM. Sydenham chorea and PANDAS in South Africa: review of evidence and recommendations for management in resource-poor countries. J Child Neurol. Published September 16, 2014.

3. Stratta P, Musetti C, Barreca A, Mazzucco G. New trends of an old disease: the acute post infectious glomerulonephritis at the beginning of the new millennium. J Nephrol. 2014;27:229-239.

4. Williams KA, Swedo SE. Post-infectious autoimmune disorders: Sydenham's chorea, PANDAS and beyond. Brain Res. Published October 7, 2014.

5. Zegers RH, Weigl A, Steptoe A. The death of Wolfgang Amadeus Mozart: an epidemiologic perspective. Ann Intern Med. 2009;151:274-278, W96-W97.

6. Cleland JB. Scarlet fever. Br Med J. 1971;2:224-225.

7. Doshi S, Maniar R, Banwari G. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). Indian J Pediatr. Published December 12, 2014.

8. Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic pain. Consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007;12:13-22.

9. Watson CPN. Herpes zoster and postherpetic neuralgia. CMAJ. 2010;182:1713-1714.

10. Oxman MN, Levin MD, Johnson JR, et al. A vaccine to prevent postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271-2284.

11. Hechter RC, Tartof SY, Jacobsen SJ, Smith N, Tseng HF. Trends and disparity in zoster vaccine uptake in a managed care population. Vaccine. 2013;31:4564-4568.

12. Lam NN, Fleet JL, McArthur E, Blake PG, Garg AX. Higher dose versus lower dose of antiviral therapy in the treatment of herpes zoster infection in the elderly: a matched retrospective population-based cohort study. BMC Pharmacol Toxicol. 2014;15:48.

13. Gilron I, Max B. Combination pharmacotherapy for neuropathic pain: current evidence and future directions. Expert Rev Neurother. 2005;5:823-830.

14. Fridkin S, Baggs J, Fagan R, et al. Vital signs: improving antibiotic use among hospitalized patients. MMWR. 2014;63:194-200.

15. Barclay L. Guidelines: antibiotics for all but very mild C difficile. Medscape [serial online]. www.medscape.com/viewarticle/813521. Accessed January 10, 2015.

16. Kling J. Low-dose vancomycin effective against C difficile. Medscape Medical News [serial online]. www.medscape.com/viewarticle/811555. Accessed October 9, 2013