The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

Kirkcaldy, Robert D.; Weinstock, Hillard; Moore, Page C.; Philip, Susan; Wiesenfeld, Harold C.; Papp, John R.; Kerndt, Peter R.; Johnson, Shacondra M.; Ghanem, Khalil G.; Hook, Edward W.; Newman, Lori M.; Dowell, Deborah; Deal, Carolyn D.; Glock, Jonathan; Venkatasubramanian, Lalitha; McNeil, Linda M.; Perlowski, Charlotte; Lee, Jeannette; Lensing, Shelly; Trainor, Nikole; Fuller, Shannon; Herrera, Amelia; Carlson, Jonathan S.; Harbison, Hanne S.; Lenderman, Connie; Dixon, Paula; Whittington, A M; Macio, Ingrid; Priest, Carol L.; Jett, Abi; Campbell, Tracy; Uniyal, Apurva; Royal, LaShawnda; Mejia, Marisol; Vonghack, Jennifer; Tobias, Susan; Zenilman, Jonathan M.; Long, Jill; Harvey, Alesia; Pettus, Kevin; Sharpe, Samera

doi:10.1093/cid/ciu521

Cited by 130 publications

(125 citation statements)

References 26 publications

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“…Preliminary findings from a recent American study examining the effectiveness of the combination of gentamicin with azithromycin suggested high efficacy of this regimen (11). However, this study did not determine the efficacy of the individual antibiotics or of gentamicin for extragenital infections.…”

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confidence: 91%

“…Gentamicin has been used for the past 2 decades in the management of gonorrhea in Malawi (8,9). Gentamicin has been considered an option for the treatment of infections due to the MDR and XDR strains and for future treatment of gonorrhea particularly in dual therapy in other geographic regions (10)(11)(12).…”

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confidence: 99%

“…Gentamicin is an effective and inexpensive and a relatively safe antibiotic that has shown high in vivo efficacy in Malawi and the United States (9,11). ESC-resistant gonococci are unlikely to exhibit cross-resistance to gentamicin, as cephalosporins act on bacterial cell wall synthesis, whereas gentamicin disrupts protein synthesis.…”

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confidence: 99%

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Gentamicin Susceptibility among a Sample of Multidrug-Resistant Neisseria gonorrhoeae Isolates in India

Bala

Singh

Bhargava

et al. 2016

Antimicrob Agents Chemother

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bAntimicrobial susceptibility testing of 258 Neisseria gonorrhoeae isolates by Etest determined that 60.1% were multidrug resistant (MDR), while 5% of the strains had decreased susceptibility to currently recommended extended-spectrum cephalosporins (ESCs). Among these, 84.5% of MDR strains and 76.9% of strains that had decreased susceptibility to ESCs were susceptible to gentamicin. No MDR isolate was resistant to gentamicin. These in vitro results suggest that gentamicin might be an effective treatment option for the MDR strains and in dual therapy for gonorrhea. However, further research regarding the clinical treatment outcomes is essential. N eisseria gonorrhoeae clinical isolates resistant to extendedspectrum cephalosporins (ESCs), the last remaining options for empirical therapy, and most other antimicrobials have been reported worldwide in recent years (1-4). Organizations such as the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC) are considering infections caused by multidrug-resistant (MDR) and extensively drugresistant (XDR) N. gonorrhoeae major public health problems (5-7). With the increasing prevalence of drug resistance, there is an urgent need for new and effective treatment options. Gentamicin has been used for the past 2 decades in the management of gonorrhea in Malawi (8, 9). Gentamicin has been considered an option for the treatment of infections due to the MDR and XDR strains and for future treatment of gonorrhea particularly in dual therapy in other geographic regions (10-12).Earlier studies focused on the in vitro susceptibility of N. gonorrhoeae to gentamicin (8,(13)(14)(15)(16)(17). Some of these studies were on a limited number of isolates (13,17). To the best of our knowledge, no study has analyzed the in vitro susceptibility of gentamicin against MDR strains. Therefore, this study was aimed at determining the (i) trend of in vitro susceptibility of N. gonorrhoeae isolates to gentamicin during 2010 to 2015, (ii) status of gentamicin susceptibility for MDR strains and strains with decreased susceptibility to ESCs, and (iii) profile of gentamicin-less-susceptible (LS) strains for eight other antimicrobials recommended currently and in the past for treatment of gonorrhea.A total of 258 N. gonorrhoeae isolates obtained from consecutive patients attending a sexually transmitted disease (STD) clinic from August 2010 to December 2015 were identified on the basis of colony morphology, Gram staining, and oxidase, superoxol, and carbohydrate utilization tests (18). Susceptibility testing for gentamicin and other antimicrobials, such as ESCs (ceftriaxone, cefpodoxime, cefixime), penicillin, tetracycline, ciprofloxacin, spectinomycin, and azithromycin, was performed using the Etest strip per manufacturer instructions (bioMérieux SA, France) on GC agar (Becton, Dickinson and Company [BD], Sparks, MD) containing 1% vitamin growth supplement (HiMedia, India) or Isovitalex (BD). Susceptibilit...

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confidence: 91%

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confidence: 99%

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Gentamicin Susceptibility among a Sample of Multidrug-Resistant Neisseria gonorrhoeae Isolates in India

Bala

Singh

Bhargava

et al. 2016

Antimicrob Agents Chemother

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“…However, there were no antagonistic outcomes with either of the antibiotics when used to assess the in vitro growth of N. gonorrhoeae, and this may be an important observation for using fluoroquinolones other than ciprofloxacin in combination with azithromycin. A recently completed clinical trial demonstrated 100% and 99.5% successes in patients with uncomplicated gonorrhea infections receiving azithromycin combined with gentamicin or gemifloxacin, respectively (8). In vitro assessments with antibiotic combinations were not performed in that study, but our data support the observed clinical utility of these antibiotic combinations.…”

mentioning

confidence: 57%

In Vitro Assessment of Dual Drug Combinations To Inhibit Growth of Neisseria gonorrhoeae

Pettus¹,

Sharpe²,

Papp³

2015

Antimicrob Agents Chemother

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The development of resistance to first-line antimicrobial therapies has led to recommendations for combination therapies for the treatment of gonorrhea infection. Recent studies have shown the success of combination therapies in treating patients, but few have reported on thein vitroactivities of these drug combinations. Anin vitroassessment of azithromycin in combination with gentamicin demonstrated inhibition of growth and suggests that clinical trials may be warranted to assess the utility of this combination in treating gonorrhea infections.

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“…Injectable ceftriaxone, in combination with oral azithromycin, is now the last antibiotic remaining as recommended firstline treatment [7]. Although other antibiotics are being tested for their safety and efficacy for N. gonorrhoeae treatment [8], no new classes of antibiotics are currently available [4] and management of antibiotics is urgently needed to preserve their efficacy. The current management strategy tries to counteract resistance spread by expanded screening and treatment of hosts [9,10], but the outcome of this strategy is uncertain.…”

Section: Introductionmentioning

confidence: 99%

Antibiotic-resistant Neisseria gonorrhoeae spread faster with more treatment, not more sexual partners

Fingerhuth

Bonhoeffer²,

Low

et al. 2015

Preprint

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The sexually transmitted bacterium Neisseria gonorrhoeae has developed resistance to all antibiotic classes that have been used for treatment and strains resistant to multiple antibiotic classes have evolved. In many countries, there is only one antibiotic remaining for empirical N. gonorrhoeae treatment and antibiotic management to counteract resistance spread is urgently needed. Understanding dynamics and drivers of resistance spread can provide rationales for antibiotic management. In our study, we first used antibiotic resistance surveillance data to estimate the rates at which antibiotic-resistant N. gonorrhoeae spread in two host populations, heterosexual men (HetM) and men who have sex with men (MSM). We found higher rates of spread for MSM (0.86 to 2.38 y −1 , mean doubling time: 6 months) compared to HetM (0.24 to 0.86 y −1 , mean doubling time: 16 months). We then developed a dynamic transmission model to reproduce the observed dynamics of N. gonorrhoeae transmission in populations of heterosexual men and women (HMW) and MSM. We parameterized the model using sexual behavior data and calibrated it to N. gonorrhoeae prevalence and incidence data. In the model, antibiotic-resistant N. gonorrhoeae spread with a median rate of 0.88 y −1 in HMW and 3.12 y −1 in MSM. These rates correspond to median doubling times of 9 (HMW) and 3 (MSM) months. The model shows the difference in the host population's treatment rate rather than the difference in the number of sexual partners explains the differential spread of resistance. As higher treatment rates result in faster spread of antibiotic resistance, treatment recommendations for N. gonorrhoeae should carefully balance prevention of infection and avoidance of resistance spread.

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The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

Cited by 130 publications

References 26 publications

Gentamicin Susceptibility among a Sample of Multidrug-Resistant Neisseria gonorrhoeae Isolates in India

Gentamicin Susceptibility among a Sample of Multidrug-Resistant Neisseria gonorrhoeae Isolates in India

In Vitro Assessment of Dual Drug Combinations To Inhibit Growth of Neisseria gonorrhoeae

Antibiotic-resistant Neisseria gonorrhoeae spread faster with more treatment, not more sexual partners

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