Chiefs’ Inquiry Corner – 10/4/2021

October 5, 2021

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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  According to the CDC, NIH and IDSA guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, patients with HIV who are not receiving ART or who remain viremic on ART but have no current options for a fully suppressive ART regimen should receive chemoprophylaxis against disseminated MAC disease if they have CD4 counts < 50 cells/mm3. Primary prophylaxis against disseminated MAC is not recommended for patients with HIV who immediately initiate ART. Primary MAC prophylaxis, if previously initiated, should be discontinued in patients who are continuing on a fully suppressive ART regimen, regardless of CD4 count. This updated recommendation is based on data from recent observational cohort studies that found no increased risk of developing MAC in patients taking suppressive ART with or without addition of MAC prophylaxis. Additional arguments against primary MAC prophylaxis include the potential for increased cost, drug adverse effects, and, for the small number of HIV patients who might develop “unmasking MAC IRIS” after starting ART, the use of monotherapy for MAC prophylaxis may result in acquired drug resistance in those with active MAC disease.

References: NIH | Mycobacterium avium complex disease
  Macrolides are among some of the most widely prescribed antibiotics for a variety of indications; some conditions they treat, such as non-tuberculosis Mycobacterial infections, require prolonged courses. Although previous studies have suggested ototoxicity (hearing loss, tinnitus) as an adverse effect of macrolide therapy (usually reversible, but occasionally permanent), the data has been inconsistent and thus such side effects are not always taken into account when prescribers counsel and monitor patients on macrolide therapy. Results from cross-sectional and longitudinal analyses of macrolide-associated ototoxicity in the Rotterdam Study [a prospective cohort study begun in 1989 in the Netherlands to examine the effects of aging] demonstrated that macrolide use was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46) after adjusting for factors such as blood pressure, diabetes, renal function, and co-administration of known ototoxic medications. Risk was increased in people receiving intermediate- and long-acting macrolides, and those who reported daily versus intermittent tinnitus. While this higher likelihood of prevalent tinnitus was associated with ever-use of macrolides, and the association was noted after short-term use (1-14 defined daily doses [DDDs]), it reached statistical significance from cumulative doses of 14 DDDs onwards, suggesting a dose-response relationship. While macrolide therapy remains a cornerstone of therapy for multiple conditions, prescribers should remain mindful that ototoxicity can be an adverse effect of these common drugs, and those with heightened risk (such as older age, pre-existing tinnitus or hearing loss, and/or use of concomitant ototoxic medications) should be counseled to monitor for these symptoms, particularly if a prolonged course of therapy is planned. Of note, the mechanism underlying this ototoxicity remains poorly understood but is likely to be multifactorial, including interference by the drug with ion transport mechanisms in cochlear cells. 

References: Macrolide-associated ototoxicity: a cross-sectional and longitudinal study to assess the association of macrolide use with tinnitus and hearing loss.
 Urine dipstick testing is a widely utilized method for detecting microscopic hematuria in urine specimens. Commonly used commercial tests utilize a benzidine compound reduced with a buffered organic peroxide; when the test trip is exposed to an oxidizing substrate in urine, a color reaction occurs. In the case of hemoglobin, pseudoperoxidase activity oxidizes the benzidine compound. Since a positive result depends on the presence of any oxidizing substrate, not just those present in blood, and other compounds can interfere with the oxidation reaction that would otherwise occur, false positives and false negatives, respectively, can occur. Examples of substances in urine other than blood that can cause a false positive include free hemoglobin and myoglobin, semen, peroxidases from vegetable or bacterial sources. Examples of substances that can cause a false negative include ascorbic acid (vitamin C) and captopril (and other sulfhydryl-containing compounds); in addition, a pH < 5.1 and/or the presence of proteinuria can also produce a false negative result. For this reason, any heme-positive dipstick test must be followed up by microscopic examination to confirm true hematuria, with additional testing required to potentially determine its cause. Despite the potential for false negative and false positive results, the urine dipstick test remains useful in initial assessment for hematuria, as it is inexpensive, widely available, and a fairly rapid test, with a sensitivity for 1+ blood or greater of 91-100% and specificity of 65-99%.

References: American Family Physician- Urinalysis: A Comprehensive Review