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Department of Defense (DOD) is assembling a group of at least 10 medical centers to study “secondary” bacterial and fungal infections in these patients and the antibiotics being used to prevent them. Crushing coronavirus means ‘breaking the habits of a lifetime.’ Behavior scientists have some tips.

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Hospitals, particularly intensive care units, are hotbeds of antimicrobial resistance, and they have long been struggling to rein in the use of antibiotics. Centers for Disease Control and Prevention requires medical centers to report their antibiotic use and the rates of infections acquired in the facility, Nori and other physicians say compliance has fallen off in the pandemic.

Some researchers suggest the pandemic could slow the spread of both bacteria and antibiotic resistance within hospitals.

Surgeries, which account for many hospital-acquired infections, have largely been canceled to keep beds open for COVID-19 patients, and hospital staff routinely wear robes, masks, and other personal protective equipment (PPE) during patient care. “Nothing gets people’s attention like a

new

But Bo Shopsin, an infectious disease physician at New York University’s Langone Health Center who is involved in DOD’s planned study, notes that some hospitals are being forced to reuse PPE and share ventilators between patients.

“It’s quite clear that COVID is transmitting in hospitals and if it is, [resistant bacteria are] too.” More important, antibiotic use appears to be surging. Several recent studies from China suggest that nearly all serious cases of COVID-19 are treated with antibiotics, and anecdotally, many U.S.

But often the antibiotics are necessary, researchers say.

Many COVID-19 patients die of secondary infections rather than the virus itself, growing evidence suggests. A recent paper in The Lancet detailing the outcomes of 247 hospitalized COVID-19 patients in Wuhan, China, found that 15% of them—and half of those who died—acquired bacterial infections.

Major outbreaks of other respiratory viruses illustrate the concern: up to half the 300,000 people who died of the 2009 H1N1 flu and the majority of deaths from the 1918 flu actually died of bacterial pneumonia.

“We do have some guidelines on when to treat and when not to treat,” says Leopoldo Segal, a pulmonologist at Langone.” But in the current situation, it’s hard to imagine those guidelines are totally applicable.” Several of his COVID-19 patients, he says, have antibiotic-resistant infections, and nearly all are receiving azithromycin: a widely used antibiotic that kills both of the two major classes of bacteria.

In combination with the antimalarial drug hydroxychloroquine, azithromycin has become a popular treatment for COVID-19 patients after President Donald Trump and others highlighted small, uncontrolled studies that appeared to show the combination was effective. It is impossible to know how often the combination is prescribed, but the rate is high enough to have caused an azithromycin shortage in the United States. Infectious disease physician Marisa Holubar of Stanford University says it’s still too early to know the extent to which COVID-19 will affect global antibiotic resistance rates.

But in some parts of the United States, 30% to 40% of some common types of bacteria were already resistant to the class of drugs that includes azithromycin, and overuse could render those or other antibiotics even less effective. “In terms of a nightmare scenario, it’s quite scary,” Clancy says. The DOD

study

The results should help experts develop guidelines for when and how doctors should prescribe antibiotics to COVID-19 patients, as well as provide a data set on potentially thousands of

patients

Linda French, MD Michigan State University, East Lansing, Mich.

Jennifer Horton, DO Genesys Regional Medical Center Family Practice Residency, Grand Blanc, Mich. Michelle Matousek, DO Henry Ford Health System, Detroit, Mich.

Hillier SL, Lipinski C, Briselden AM, Eschenbach DA.

Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis.

Comparison of different metronidazole therapeutic regimens for bacterial vaginosis.

Ferris DG, Litaker MS, Woodward L, Mathis D, Hendrich J. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. Fischbach F, Petersen EE, Weissenbacher ER, Martius J, Hosmann J, Mayer H. Efficacy of clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis.

Hillier S, Krohn MA, Watts DH, Wolner-Hanssen P, Eschenbach D. Microbiologic efficacy of intravaginal clindamycin cream for the treatment of bacterial vaginosis.

Effect of early oral clindamycin on late miscarriage and preterm

delivery

Mikamo H, Kawazoe K, Izumi K, Watanabe K, Ueno K, Tamaya T. Comparative study on vaginal or oral treatment of bacterial vaginosis. The treatment of bacterial vaginosis with a 3 day course of 2% clindamycin cream: results of a multicentre, double blind, placebo controlled trial. Bacterial vaginosis: treatment with clindamycin cream versus oral metronidazole. Vaginal clindamycin and oral metronidazole for bacterial vaginosis: a randomized trial.

In vitro activities of 10 antimicrobial agents against bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women.

Shalev E, Battino S, Weiner E, Colodner R, Keness Y. Ingestion of yogurt containing Lactobacillus acidophilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis.

The efficacy of vaginal clindamycin for the treatment of abnormal genital tract flora in pregnancy.

A comparative clinical evaluation of econazole nitrate, miconazole, and nystatin in the treatment of vaginal candidiasis. Placebo controlled trial of itraconazole for treatment of acute vaginal candidiasis.

Van der Pas H,

Peeters

Treatment of vaginal candidosis with oral ketoconazole.

Randomized comparative trial of three regimens of itraconazole for treatment of vaginal mycoses. Itraconazole versus placebo in the management of vaginal candidiasis. Watson MC, Grimshaw JM, Bond CM, Mollison J, Ludbrook A. Oral versus intravaginal imidazole and triazole anti-fungal agents for the treatment of uncomplicated vulvovaginal candidiasis (thrush): a systematic review. Single-dose oral fluconazole versus single-dose topical miconazole for the treatment of acute vulvovaginal candidosis.

Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole.

Creatsas GC, Charalambidis VM, Zagotzidou EH, Anthopoulou HN, Michailidis DC, Aravantinos DI. Chronic or recurrent vaginal candidosis: short-term treatment and prophylaxis with

itraconazole

Singh S, Sobel JD, Bhargava P, Boikov D, Vazquez JA. Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy. Cross-Resistance of clinical isolates of Candida albicans and Candida glabrata to over-the-counter azoles used in the treatment of vaginitis. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy.

Interventions for treating trichomoniasis in women.

A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis.

Tidwell BH, Lushbaugh WB, Laughlin MD, Cleary JD, Finley RW.

A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis.

The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study. Clinical and microbiological aspects of Trichomonas vaginalis. Trichomoniasis: trends in diagnosis and management. Intravenous therapy of metronidazole-resistant Trichomonas vaginalis.

An incremental dosing protocol for women with severe vaginal trichomoniasis and adverse reaction to metronidazole. Nyirjesy P, Sobel JD, Weitz MV, Leaman DJ, Gelone SP.

Difficult-to-treat trichomoniasis: results with paromomycin cream. Tinidazole therapy for metronidazole resistant vaginal trichomoniasis. Antifungal medications for intravaginal use have been available in the United States for more than a decade.

Women may be inclined to self-diagnose yeast infections with any vaginal discharge or other vulvovaginal symptoms that they deem abnormal.

As we saw in the first part of this article, “Abnormal vaginal discharge: Using office diagnostic

testing

vaginosis

also

The standard treatment for bacterial vaginosis (BV) has been oral metronidazole (Flagyl) 500 mg twice daily for 5 to 7 days. Intravaginal 0.75% metronidazole gel (MetroGel) has been shown to be as effective as oral metronidazole (SOR: A amoxicillin 1 gm ). Oral metronidazole can cause nausea and abdominal pain in some patients; vaginal treatment may be preferable for them.

A meta-analysis of 52 studies of regimens of oral metronidazole at a dose of 2 g daily of varying duration showed similar initial cure rates of 85%, 87%, 86%, and 87% for 1, 2, 5, and 7 days, respectively (strength of recommendation [SOR]: A ).

3 Single-dose therapy may improve adherence (SOR: C ). Clindamycin (Cleocin), orally or in vaginal cream, for 5 days is also effective for BV (SOR: A ).

4-8 Clindamycin cream is used at a dose of 5 g daily and a concentration of 2%.

6 Oral regimens range from 300 mg twice daily to 450 mg 3 times daily.

Oral and vaginal preparations have shown equal efficacy in direct comparisons (SOR: A ).

8 A 3-day course of vaginal clindamycin is as effective as a 5-day course (SOR: B ).

Several studies have compared clindamycin and metronidazole head to head.

They have shown similar cure rates that were not statistically different in the 75% to 90% range (SOR: A ).

4,5,10,11 Other antibiotics that have shown in vitro efficacy for treating the spectrum of microbes associated with BV are amoxicillin-clavulanate (Augmentin), imipenem (Primaxin), and cefmetazole (Zefazone) (SOR: C ). 8,12 Some Mobiluncus strains show resistance to metronidazole (SOR: C ).

The initial regimen or an alternative regimen may be used.

A longer, 10- to 14-day, course of antibiotic therapy has been recommended by one expert for treating relapses (SOR: C ). 13 Recolonizing the vagina with lactobacilli by eating yogurt or using bacteria-containing suppositories is an approach that deserves further study (SOR: C ).

14 Suppressive therapy such as intravaginal metronidazole twice weekly may also be considered as maintenance therapy to prevent recurrences (SOR: C ). A number of studies have been published on screening for BV in pregnancy using Gram stain and on treating positive cases with antibiotics.

While studies that used metronidazole for treatment have not shown consistently good results, more recent studies using clindamycin orally or intravaginally have been promising (SOR: B ). 7,15 Oral dosing at 300 mg twice daily, at 12 to 22 weeks gestation, has reduced preterm delivery for pregnant women with BV diagnosed by Nugent’s criteria (number needed to treat [NNT]=10). 7 Likewise, for women with BV treated at 13 to 20 weeks gestation, intravaginal clindamycin therapy for 3 days has reduced the incidence of preterm births (NNT=17).

Clindamycin appears to be the treatment of choice for BV in pregnancy (SOR: C ) since it is considered safe (category B) throughout pregnancy, and because use of metronidazole in the first trimester is controversial. Treating vulvovaginal candidiasis (VVC) with intravaginal imidazoles reduces symptoms with NNT=3 after 1 month (SOR: A ) ( Table ).