Desmopressin Nasal Spray for Treatment of Nocturia: Proceed With Caution

SOURCE: Fralick M, Kesselheim AS. JAMA 2017;317:2059-2060.

Nocturia is a symptom than can reflect a variety of underlying pathologies, including heart failure, diabetes, and benign prostatic hyperplasia. Although it might be tempting to go directly to pharmacologic treatment, with the recent approval of an agent designed to treat such symptoms, caution is in order. The indication for the recently approved desmopressin nasal spray (Noctiva) is specified for “treatment of nocturia due to nocturnal polyuria in adults who awaken at least two times per night to void.” Fralick and Kesselheim reinforced the FDA labeling, indicating that the use of desmopressin should be preceded by elimination of underlying serious pathology (e.g., bladder cancer, pituitary pathology) as well as confirmation of polyuria with a 24-hour urine collection.

Adverse effects of desmopressin include hyponatremia, which can be severe. Although clinical trial data demonstrated severe hyponatremia (≤ 125 mmol/L), only rare (0.7% of desmopressin recipients vs. 0.3% of placebo subjects), moderate hyponatremia (126-129 mmol/L) is substantially more common (2.2% of desmopressin subjects vs. no placebo subjects). Finally, the mean change in nocturia episodes decreased from about 3.3 episodes per night to about 1.9/night with desmopressin treatment, which many of us might consider only a modest symptomatic improvement.

Because desmopressin can result in serious adverse events, it is important that clinicians become fully familiar with FDA labeling of the new product and be confident that no underlying serious pathology is present before prescribing.


Efficacy of Cephalexin Monotherapy for Cellulitis

SOURCE: Moran GJ, Krishnadasan A, Mower WR, et al. JAMA 2017;317:2088-2096.

The past decade has seen methicillin-resistant Staphylococcus aureus (MRSA) maintain sufficient prevalence in cases of acute cutaneous abscesses that treatment oriented to that pathogen, typically trimethoprim-sulfamethoxazole or doxycycline, has become routine adjunctive treatment to incision and drainage. The pathogen responsible for cellulitis without abscess often has been assumed to involve MRSA frequently, leading to similar treatment regimens. Although nailing down with certainty the etiologic agent of cellulitis presents greater difficulty than an abscess, the currently predominant cellulitis pathogen is believed to be beta-hemolytic strep. In typical clinical settings, the pathogen usually is not identified prior to treatment initiation. If MRSA is not a major player in simple cellulitis (without abscess), might agents to address MRSA be omitted safely?

A randomized, clinical trial of cellulitis patients (n = 500) without evidence of abscess compared cephalexin + trimethoprim-sulfamethoxazole to cephalexin monotherapy. The primary outcome was clinical cure.

There was no statistically significant difference in the primary outcomes for the two groups, with a higher than 80% success rate in both treatment arms. In the absence of evidence of purulent infection, these data support the use of cephalexin treatment (500 mg four times daily for seven days) as a simpler, less expensive antimicrobial regimen.


Combination Treatment for Patients Hospitalized With Influenza

SOURCE: Hung IFN, To KKW, Chan JFW, et al. Chest 2017;15:1069-1080.

Was I the only clinician who was unaware that either clarithromycin or naproxen possess antiviral activity? In their opening discussion of the topic, Hung et al commented, “In vitro and animal studies have shown that ... clarithromycin and naproxen ... both possess antiviral activity. ... In addition, macrolides have effects on the host response to influenza virus infection.” Who knew?

In the United States, thousands of people die each year from influenza. The effect of “traditional” antiviral therapy, most commonly neuraminidase inhibitors, often is limited by the fact that patients are admitted more than 48 hours after symptom onset, rendering neuraminidase inhibitors less effective.

Patients admitted to the hospital (n = 217) with confirmed influenza A (H3N2) were randomized to five days of treatment with oseltamivir 75 mg twice daily, plus either clarithromycin 500 mg + naproxen 200 mg twice daily for the first two days or placebo.

There was a dramatic, statistically significant effect of the combination therapy on mortality. Of the 10 deaths in the 30-day follow-up, nine were in the neuraminidase monotherapy group. Confirming that this is unlikely to be related to the antibacterial effects of clarithromycin, the authors indicated that < 5% of these patients had confirmation of bacterial coinfection at presentation. Clinicians may want to consider such a regimen for hospitalized influenza pneumonia patients.