Research and business - the yin and yang in modern medicine.

Yin and yang is a concept of dualism in Chinese philosophy, describing how opposite or contrary forces may be complementary, interconnected and interdependent, and how they may give rise to each other as they interrelate with one another. In line with this, modern clinical research and business can definitely be described as yin and yang. With the increasing need for funding, researchers at a very early stage during the development of a new concept may be forced or tempted to enter the business world. Furthermore, researchers are encouraged and supported by their own universities to collaborate with possible future business partners, not only to acquire funding, but also to explore potential patenting. This collaboration between the business world and research can definitely be very fruitful and provide benefit for both parties, patients and society as a whole, but it may also introduce the risk of premature materialization.

Susceptibility patterns in Neisseria gonorrhoeae in Nuuk, Greenland, 2015-2018: a short communication.

Antimicrobial resistance in Neisseria gonorrhoeae (GC) has made gonorrhoea control and treatment more complex globally. In Greenland, the incidence of gonorrhoea is high and there is a need for continued surveillance of antimicrobial susceptibility.This study investigated gonococcal isolates obtained in Greenland's capital Nuuk between January 2015 and June 2018. Subsequent to collection, isolates were tested for ciprofloxacin and ceftriaxone susceptibility in order to monitor the resistance pattern among GC strains. 150 GC strains were isolated in Nuuk during the observation period (139 males, 93%; 11 females, 7%). All strains were fully susceptible to ceftriaxone. 49% of the GC strains were susceptible to ciprofloxacin. The median minimal inhibitory concentration (MIC) for ceftriaxone among GC strains resistant to ciprofloxacin was higher than among GC strains susceptible to ciprofloxacin. No differences in ciprofloxacin susceptibility and median MICs for ceftriaxone were observed by collection year. In conclusion no ceftriaxone resistance has been found in Nuuk to date. Continued easy access to diagnostics and treatment combined with increased and more systematic surveillance of antimicrobial susceptibility in Nuuk is recommended. Further, it is advisable to investigate the possibilities for intermittent sampling in Greenland outside of Nuuk, if obstacles in relation to sending sampling material to Nuuk can be bypassed.

Macrolide-resistant Mycoplasma genitalium infections in Cuban patients: an underestimated health problem.

BACKGROUND: The increasing prevalence of macrolide resistant Mycoplasma genitalium is a major concern worldwide. In Cuba, several cases of clinical treatment failure with 1 g single dose and extended azithromycin regimen have been detected and the aim of the present investigation was to retrospectively determine the prevalence of macrolide-resistance mediating mutations (MRMM) in M. genitalium-positive samples conserved at the Cuban National Reference Laboratory of Mycoplasma Research between 2009 and 2016. METHODS: A total of 280 positive DNA extracts were analysed by a 5' nuclease assay for detection of M. genitalium MRMM. Ten urogenital specimens from patients with azithromycin treatment failure and MRMM were inoculated in Vero cell to obtain the isolates for subsequent determination of antimicrobial susceptibility. RESULTS: The overall prevalence of MRMM was 32%. No MRMM was detected in samples collected between 2009 and 2013 but since 2014 a dramatic increase to 90% (95% CI, 76-96%) in 2016 was seen. Three new M. genitalium isolates were isolated in Vero cell cultures and confirmed phenotypic resistance to macrolides in a cell-culture assisted susceptibility test. Preliminary observations suggest that combination therapy with levofloxacin and doxycycline may represent an affordable option for treatment of macrolide resistant M. genitalium infections. CONCLUSIONS: This investigation showed the rapid emergence and high prevalence of MRMM in M. genitalium-infected patients in Cuba and confirmed the phenotypic resistance in isolates carrying MRMM. We suggest that Cuban guidelines for sexually transmitted infections are modified to include testing for M. genitalium and detection of MRMM in patients with failure of syndromic treatment, to ensure that in these cases, the treatment will be guided by etiologic diagnosis.

Efficacy of Antimicrobial Therapy for Mycoplasma genitalium Infections.

Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed.

Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women.

OBJECTIVES: The objectives of this study were to evaluate the time to a Mycoplasma genitalium-negative test after start of treatment and to monitor if and when antibiotic resistance developed. METHODS: Sexually transmitted disease (STD) clinic attendees with suspected or verified M. genitalium infection were treated with azithromycin (5 days, 1.5 g; n = 85) or moxifloxacin (n = 5). Subjects with symptomatic urethritis or cervicitis of unknown aetiology were randomized to either doxycycline (n = 49) or 1 g of azithromycin as a single dose (n = 51). Women collected vaginal specimens and men collected first-catch urine 12 times during 4 weeks. Specimens were tested for M. genitalium with a quantitative MgPa PCR and for macrolide resistance-mediating mutations with a PCR targeting 23S rRNA. CLINICAL TRIALS REGISTRATION: NCT01661985. RESULTS: Ninety M. genitalium cases were enrolled. Of 56 patients with macrolide-susceptible strains before treatment with azithromycin (1.5 g, n = 46; 1 g single oral dose, n = 10), 54 (96%) had a negative PCR test within 8 days. In four patients, M. genitalium converted from macrolide susceptible to resistant after a 10 day lag time with negative tests (azithromycin 1.5 g, n = 3; 1 g single oral dose, n = 1). Moxifloxacin-treated subjects (n = 4) were PCR negative within 1 week. Six of eight (75%) remained positive despite doxycycline treatment. CONCLUSIONS: PCR for M. genitalium rapidly became negative after azithromycin treatment. Macrolide-resistant strains were detected after initially negative tests. Test of cure should be recommended no earlier than 3-4 weeks.

Management of Mycoplasma genitalium infections - can we hit a moving target?

Mycoplasma genitalium is an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few M. genitalium strains are available for determination of the activity of currently used and new antimicrobial agents.Recent clinical trials have demonstrated that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, which is likely to be attributed to the widespread use of 1 g single dose azithromycin. Second line treatment with moxifloxacin is similarly under pressure from emerging resistance. The era of single dose monotherapy for uncomplicated STIs such as M. genitalium and N. gonorrhoeae, while convenient for patients and physicians, has been associated with escalating resistance and treatment failure and is now drawing to a close. There is a critical need for trials of combinations of existing registered drugs and new antimicrobial compounds, implementation of diagnostic testing combined with molecular detection of resistance, and antimicrobial surveillance.

Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae strains in Nuuk, Greenland: time to reconsider preventive and treatment strategies.

OBJECTIVES: Sexually transmitted infections (STIs), including infections with Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011, GC testing has been performed on urine with nucleic acid amplification tests (NAATs) by strand displacement amplification (Becton Dickinson ProbeTec). Monitoring of GC antibiotic susceptibility by culture was introduced in Nuuk in 2012. Until 2014, no cases of ciprofloxacin-resistant GC strains were reported. In this paper, we report the finding of ciprofloxacin-resistant GC and describe the most recent incidence of GC infections in Greenland. METHODS: The number of urine NAATs and culture-positive swabs from January to October 2014 were obtained from the Central Laboratory at Queens Ingrid's Hospital in Nuuk and stratified on gender, place and period of testing. Incidence rates were estimated as number of urine NAAT * (12/10) per 100,000 inhabitants. Men in Nuuk with a positive NAAT for GC were encouraged to provide a urethral swab for culture and susceptibility testing. RESULTS: From January to October 2014, a total of 5,436 urine GC NAATs were performed on patients from Nuuk and 9,031 from the rest of Greenland. Of these, 422 (8%) and 820 (9%) were positive, respectively. From January to August, 6 (15%) cultures from Nuuk were ciprofloxacin resistant while in September and October, 26 (59%) were ciprofloxacin resistant (p<0.01). In total, 35 (40%) of 88 culture-positive isolates showed ciprofloxacin resistance. GC incidence in Nuuk was 3,017 per 100,000 inhabitants per year, compared to 2,491 per 100,000 inhabitants per year in the rest of Greenland. CONCLUSION: Within a short period, a rapid and dramatic change in ciprofloxacin susceptibility among GC strains isolated in Nuuk was documented and recommendation for first line treatments has changed. Continued monitoring and rethinking of primary and secondary preventive initiatives is highly recommended in this high GC incidence setting.

High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea.

We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n=250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most other currently or previously recommended antimicrobials. AZD0914 should be further evaluated, including in vitro selection, in vivo emergence and mechanisms of resistance, pharmacokinetics/pharmacodynamics in humans, optimal dosing, and performance, in appropriate randomized and controlled clinical trials.

Low prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae in Nuuk, Greenland.

During a 35-day period, 32 isolates of Neisseria gonorrhoeae strains were collected by culture from patients with positive nucleic acid amplification test results in Nuuk, Greenland, where ciprofloxacin is the preferred treatment. All isolates were quinolone susceptible, suggesting that resistance is rare. Sampling patients for culture before treatment may prove useful in reestablishing surveillance.