The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were ß-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.

Sanguinarine, similar to the MICs of spectinomycin, exhibits good anti-Neisseria gonorrhoeae activity in vitro.

The increasing antibiotic resistance of Neisseria gonorrhoeae (NG) is an urgent need to explore new and effective drugs. The antibacterial activities of spectinomycin and sanguinarine against 117 clinical NG isolates and time-kill curve of sanguinarine were evaluated. Almost all isolates were resistant to penicillin (91.5%) and ciprofloxacin (96.5%), 8.5% showed resistance to azithromycin, 10.3% and 10.3% had decreased susceptibility/resistance to ceftriaxone and cefixime, respectively, whereas 100% were susceptible to spectinomycin. The minimum inhibitory concentration (MIC) ranges, MIC50, MIC90 and MICmean values of sanguinarine were 2-64 µg/ml, 16 µg/ml, 32 µg/ml and 16.9 µg/ml, respectively, and time-kill curve showed killing of bacteria in a dose-dependent manner during the assay time of 6h, very similar to spectinomycin. Sanguinarine has great potential as an effective and novel anti-NG agent.

Associations of antimicrobial use with antimicrobial susceptibility at the calf level in bacteria isolated from the respiratory and digestive tracts of veal calves before slaughter.

OBJECTIVES: Antimicrobial drugs are frequently administered in veal calves, but investigations on associations with antimicrobial susceptibility of bacteria are scarce and convey partly contradictory findings. The aim of this study was to investigate associations of antimicrobial use (AMU) during the fattening period with antimicrobial susceptibility shortly before slaughter. METHODS: Detailed treatment data of 1905 veal calves from 38 farms were collected prospectively during monthly farm visits for 1 year (n = 1864 treatments, n = 535 visits); 1582 Escherichia coli, 1059 Pasteurella multocida and 315 Mannheimia haemolytica were isolated from rectal and nasopharyngeal swabs collected before slaughter and subjected to antimicrobial susceptibility testing by microdilution. Associations of antimicrobial treatments with resistant isolates were investigated at the calf level. RESULTS: Associations of AMU with antimicrobial resistance were observed using generalized linear models. For E. coli, the odds of being resistant were increased with increased AMU (OR 1.36 when number of treatments >1, P = 0.066). Use of tetracyclines was associated with resistance to tetracycline (OR 1.86, P < 0.001) and use of penicillins was associated with resistance to ampicillin (OR 1.66, P = 0.014). No significant associations were observed for P. multocida (use of aminoglycosides: OR 3.66 for resistance to spectinomycin, P = 0.074). For M. haemolytica, the odds of being resistant were increased with increased AMU (OR 4.63, P < 0.001), and use of tetracyclines was associated with resistance to tetracycline (OR 6.49, P < 0.001). CONCLUSIONS: Occurrence of resistant bacteria shortly before slaughter was associated with AMU in veal calves. Prudent and appropriate use may contribute to limit the selection of resistant bacteria on veal farms.

In vitro susceptibility of Mycoplasma iowae isolates to antimicrobial agents.

ABSTRACTMycoplasma iowae, a potential re-emerging avian pathogen mainly affecting turkeys, has been reported from many parts of the world. Poor hatchability, embryonic death, joint and skeletal abnormalities, poor ossification, runting-stunting, poor feathering and airsacculitis may be observed in infected flocks. The reduction of the severity of clinical signs and short-term control of M. iowae are performed by antibiotic treatment. However, M. iowae develops resistance more rapidly and is considered to be more resistant to antimicrobials than other avian pathogenic mycoplasmas. The aim of the present study was to determine the in vitro susceptibility of 101 M. iowae isolates and strains to ten clinically important antimicrobial agents, and to analyse and compare the susceptibility patterns of isolates of various origins and from a wide time-period. The examined reference strains showed high susceptibility to all antimicrobials except for spectinomycin. Low concentrations of tiamulin, florfenicol and oxytetracycline inhibited the growth of the clinical isolates. Nevertheless, slow tendency of increasing minimum inhibitory concentration (MIC) values was observed over time in the case of the above mentioned agents, while MIC values of enrofloxacin showed relatively rapid changes. Spiramycin, erythromycin, tilmicosin, tylosin, lincomycin and spectinomycin did not inhibit the bacterial growth in most of the cases. Isolates originating from captive game birds showed similar susceptibility profiles to isolates from industrial turkey hosts. The widely detected low susceptibility of M. iowae isolates to macrolides, lincomycin and spectinomycin, and the increase of MIC values of frequently used antimicrobials against this pathogen, emphasize the importance of targeted antibiotic therapy.RESEARCH HIGHLIGHTSAntimicrobial susceptibilities of 101 Mycoplasma iowae isolates were determined.Minimum inhibitory concentrations were determined by broth micro-dilution method.Tiamulin, oxytetracycline and florfenicol showed low MIC values.Isolates rapidly adapted to antimicrobial pressure.

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

Azithromycin, minocycline, moxifloxacin and spectinomycin failure in a case with persistent Mycoplasma genitalium infection in Guangzhou, China.

We report a case of Mycoplasma genitalium-positive non-gonococcal urethritis who failed to respond to multiple different courses of antibiotics including azithromycin, minocycline, moxifloxacin and spectinomycin. Extracted M. genitalium DNA from urethral swabs obtained from the patient harbored mutations of 23S rRNA, parC and gyrA. Microbiological cure was eventually achieved by a 14-day course of doxycycline.

Antimicrobial Resistance of Neisseria Gonorrhoeae in a Newly Implemented Surveillance Program in Uganda: Surveillance Report.

BACKGROUND: Neisseria gonorrhoeae (commonly known as gonorrhea) has developed resistance to all first-line therapy in Southeast Asia. East Africa has historically had absent or rudimentary gonorrhea surveillance programs and, while the existence of antimicrobial-resistant gonorrhea is recognized, the extent of its resistance is largely unknown. In 2016, the World Health Organization's Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) was initiated in Uganda to monitor resistance trends. OBJECTIVE: This study characterizes gonorrhea and antibiotic resistance in a large surveillance program of men with urethral discharge syndrome from Kampala, Uganda. METHODS: Men attending sentinel clinics with urethritis provided demographic information, behavior data, and a urethral swab in line with the World Health Organization's EGASP protocols for culture, identification, and antibiotic-sensitivity testing using 2 methods-disk diffusion (Kirby-Bauer test) and Etest (BioMérieux Inc). A subset of samples underwent detailed antimicrobial resistance testing. RESULTS: Of 639 samples collected from September 2016 to February 2018, 400 (62.6%) were culture-positive though 414 (64.8%) had microscopic evidence of gonorrhea. The mean age of the men from whom the samples were collected was 26.9 (SD 9.6) years and 7.2% (46/639) reported having HIV. There was high-level resistance to ciprofloxacin, tetracycline, and penicillin (greater than 90%) by Kirby-Bauer disk diffusion and 2.1% (4/188) had reduced azithromycin sensitivity by Etest. Of the early isolates that underwent detailed characterization, 60.3% (70/116) were culture-positive, 94% (66/69) isolates were either ciprofloxacin-resistant or ciprofloxacin-intermediate by Etest, 96% (65/68) were azithromycin-sensitive, and 96% (66/69) were gentamicin-sensitive. Resistance profiles were comparable between methods except for ceftriaxone (disk diffusion: 68/69, 99%; Etest: 67/69, 97%) and for gentamicin (disk diffusion: 2/8, 25%; Etest: 66/69, 96%) sensitivity. CONCLUSIONS: This is the first report from a systematic gonorrhea surveillance program in Uganda. Findings demonstrated resistance or increased minimum inhibitory concentration to all key antigonococcal antibiotics. There was evidence of poor antibiotic stewardship, near-universal resistance to several antibiotics, and emerging resistance to others. Individuals in the population sampled were at exceptionally high risk of STI and HIV infection requiring intervention. Ongoing surveillance efforts to develop interventions to curtail antimicrobial-resistant gonorrhea are needed.

Aminomethyl spectinomycins: a novel antibacterial chemotype for biothreat pathogens.

New antibiotics that are active against multi-drug-resistant strains and difficult-to-treat bacterial infections are needed. Synthetic modification of spectinomycin, a bacterial protein synthesis inhibitor, has been shown to increase antibacterial activity compared with spectinomycin. Aminomethyl spectinomycins are active against Gram-negative and Gram-positive bacterial pathogens. In this study, the ability of aminomethyl spectinomycins to treat biothreat pathogens is examined by MIC profiling, synergy testing, and in vivo efficacy experiments. Compound 1950 exhibited potent antibacterial activity against Gram-negative pathogens Brucella spp., Burkholderia mallei, and Francisella tularensis, but showed little to no growth inhibition against Burkholderia pseudomallei, Bacillus anthracis, and Yersinia pestis. Combination testing in checkerboard assays revealed that aminomethyl spectinomycin-antibiotic combinations had mainly an additive effect against the susceptible biodefense pathogens. The in vivo efficacy of compound 1950 was also demonstrated in mice infected with B. mallei (FMH) or F. tularensis (SchuS4). These results suggest that aminomethyl spectinomycins are promising new candidates for development of therapeutics against biodefense bacterial agents.

Efficacy of Aminomethyl Spectinomycins against Complex Upper Respiratory Tract Bacterial Infections.

The most frequent ailment for which antibiotics are prescribed is otitis media (ear infections), which is most commonly caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae Treatment of otitis media is complicated by the fact that the bacteria in the middle ear typically form biofilms, which can be recalcitrant to antibiotic treatment. Furthermore, bacterial respiratory infections can be greatly exacerbated by viral coinfection, which is particularly evidenced by the synergy between influenza and S. pneumoniae In this study, we sought to ascertain the in vivo efficacy of aminomethyl spectinomycin lead 1950, an effective antibacterial agent both in vitro and in vivo against Streptococcus pneumoniae in the context of complex respiratory infections and acute otitis media. A single dose of 1950 significantly reduced bacterial burden in the respiratory tract for all three pathogens, even when species were present in a coinfection model. Additionally, a single dose of 1950 effectively reduced pneumococcal acute otitis media from the middle ear. The agent 1950 also proved efficacious in the context of influenza-pneumococcal super infection. These data further support the development of this family of compounds as potential therapeutic agents against the common causes of complex upper respiratory tract infections and acute otitis media.

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016.

BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. RESULTS: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. CONCLUSIONS: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018.

We describe a gonorrhoea case with combined high-level azithromycin resistance and ceftriaxone resistance. In February 2018, a heterosexual male was diagnosed with gonorrhoea in the United Kingdom following sexual intercourse with a locally resident female in Thailand and failed treatment with ceftriaxone plus doxycycline and subsequently spectinomycin. Resistance arose from two mechanisms combining for the first time in a genetic background similar to a commonly circulating strain. Urgent action is essential to prevent further spread.

Resistência de Neisseria gonorrhoeae a antimicrobianos na prática clínica: como está o Brasil? / Antimicrobials resistance of Neisseria gonorrhoeae in clinical practice: where Brazil stands?

Estima-se que um milhão de infecções sexualmente transmissíveis (IST) sejam adquiridas por dia no mundo, segundo a Organização Mundial da Saúde. Elas podem ser causadas por diversos micro-organismos pelo contato sexual. Embora tratáveis, as infecções, como a clamidiana, sífilis, tricomoníase e gonorreia, são responsáveis por 350 milhões de novos casos de IST anualmente no mundo. A gonorreia é a segunda IST bacteriana mais prevalente no planeta e tem chamado atenção nos últimos anos em decorrência da baixa eficácia em seu tratamento. O agente etiológico é a Neisseria gonorrhoeae. Na maioria das mulheres, a infecção por esse micro-organismo é assintomática, dificultando ainda mais seu diagnóstico e tratamento e, portanto, aumentando o risco de desenvolvimento de suas complicações associadas. Mesmo quando diagnosticada, essa infecção está sujeita a um alto índice de insucesso terapêutico que se deve, principalmente, à grande plasticidade genética da N. gonorrhoeae para aquisição de genes cromossômicos ou plasmidiais de resistência. O aumento da resistência desse micro-organismo a antimicrobianos comumente utilizados no tratamento, como penicilina, tetraciclina e ciprofloxacina, tem sido relatado em diversos países. No Brasil, poucos estudos estão disponíveis, mas em alguns estados já foram relatadas linhagens resistentes à ciprofloxacina. Dessa forma, deve-se ressaltar a importância de novos estudos que visem descrever o perfil da resistência da N. gonorrhoeae a antimicrobianos. Tais achados certamente nortearão a implementação de sistemas de vigilância epidemiológica no país visto que, até o momento, as infecções por N. gonorrhoeae sequer estão incluídas na lista nacional de doenças e agravos de notificação compulsória.(AU)

According to the World Health Organization, approximately one million sexually transmitted infections (STI) are acquired daily in the world. These infections can be caused by several microorganisms via contact. The treatable STI, such as chlamydia, syphilis, trichomoniasis and gonorrhea, account for 350 million new cases of STI each year worldwide. Gonorrhoea is caused by Neisseria gonorrhoeae and is the second most common bacterial STI in the world. It has drawn more attention in the last years due to the low efficacy in its treatment. Most women with this infection are asymptomatic, which makes its diagnosis and treatment troublesome increasing the risk for its associated complications. Even when diagnosed, this infection is subject to a high rate of therapeutic failure mainly due to the great genetic plasticity of N. gonorrhoeae for the acquisition of chromosomal or resistance plasmid enes. Increased resistance of this microorganism to antimicrobials commonly used in treatment such as penicillin, tetracycline and ciprofloxacin has been reported in several countries. In Brazil, few studies are available, but in some states strains resistant to ciprofloxacin were alreadyreported. The refore, it is important to highlight the importance of new studies aimed at describing the resistance profile of N. gonorrhoeae to antimicrobials in Brazil context. These findings will certainly guide the implementation of epidemiological surveillance systems in the country, since until now N. gonorrhoeae infections do not figure into the national list of compulsorily notifiable diseases.(AU)

Antibiotics for treating gonorrhoea in pregnancy.

BACKGROUND: Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth, and can cause gonococcal ophthalmia neonatorum as well as systemic neonatal infections. It can also cause endometritis and pelvic sepsis in the mother. This review updates and replaces an earlier Cochrane Review on antibiotics for treating this infectious condition. OBJECTIVES: To assess the clinical effectiveness and harms of antibiotics for treating gonorrhoea in pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2017), LILACS database (1982 to April 5, 2017), the WHO International Clinical Trials Registry Platform (ICTRP; April 5, 2017), ClinicalTrials.gov (April 5, 2017), the ISRCTN Registry (April 5, 2017), and Epistemonikos (April 5, 2017). We also searched reference lists of all retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the use of antibiotics for treating gonorrhoea in pregnancy. The antibiotics could have been used alone or in combination, were administered parenterally, orally, or both, and were compared with another antibiotic.We included RCTs regardless of their publication status (published, unpublished, published as an article, an abstract, or a letter), language, or country. We applied no limits on the length of follow-up.We excluded RCTs using a cluster- or cross-over design, or quasi-RCTs. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. MAIN RESULTS: We included two RCTs, that randomised 514 pregnant women (347 women analysed) at a mean gestational age of 22 weeks. Both trials were conducted in the outpatient department of the same two hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One of the trials was sponsored by a drug company. We considered both trials to be at a high risk of bias.One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include the spectinomycin data because this medication is no longer produced. We were unable to conduct meta-analysis because the trials compared different medications.We found inconclusive evidence that there were clear differences in the cure of gonococcal infections (genital, extragenital, or both) between intramuscular ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91 to 1.08; one RCT; 95 women; very low-quality evidence).Neither of the trials reported on two of this review's primary maternal outcomes: incidence of obstetric complications (miscarriage, premature rupture of membranes, preterm delivery, or fetal death), or disseminated gonococcal infection, or on the incidence of neonatorum ophthalmia in the neonates.One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not quantify it. Hyperberbilurrubinemia was more frequent in neonates whose mothers were exposed to ceftriaxone. There were no clear differences between groups for neonatal malformation. AUTHORS' CONCLUSIONS: This Cochrane Review found high levels of cure of gonococcal infections in pregnancy with the given antibiotic regimens. However, the evidence in this review is inconclusive as it does not support one particular regimen over another. This conclusion was based on very low-quality evidence (downgraded for poor trial design, imprecision) from two trials (involving 514 women), which we assessed to be at a high risk of bias for a number of domains. The harm profiles of the antibiotic regimes featured in this review remain unknown.High-quality RCTs are needed, with sufficient power to assess the clinical effectiveness and potential harms of antibiotics in pregnant women with gonorrhoea. These should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient-Centered Outcomes Research Institute (PCORI) outcomes.

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections.

Bacterial sexually transmitted infections are widespread and common, with Neisseria gonorrhoeae (gonorrhea) and Chlamydia trachomatis (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy, and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial coinfections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections. The need for new antibiotics is great, but the pipeline for new drugs is alarmingly small. The aminomethyl spectinomycins, a new class of semisynthetic analogs of the antibiotic spectinomycin, were developed on the basis of a computational analysis of the spectinomycin binding site of the bacterial 30S ribosome and structure-guided synthesis. The compounds display particular potency against common respiratory tract pathogens as well as the sexually transmitted pathogens that cause gonorrhea and chlamydia. Here, we demonstrate the in vitro potencies of several compounds of this class against both bacterial species; the compounds displayed increased potencies against N. gonorrhoeae compared to that of spectinomycin and, significantly, demonstrated activity against C. trachomatis that is not observed with spectinomycin. Efficacies of the compounds were compared to those of spectinomycin and gentamicin in a murine model of infection caused by ceftriaxone/azithromycin-resistant N. gonorrhoeae; the aminomethyl spectinomycins significantly reduced the colonization load and were as potent as the comparator compounds. In summary, data produced by this study support aminomethyl spectinomycins as a promising replacement for spectinomycin and antibiotics such as ceftriaxone for treating drug-resistant gonorrhea, with the added benefit of treating chlamydial coinfections.

Aminoglycoside susceptibility of Pasteurella multocida isolates from bovine respiratory infections in China and mutations in ribosomal protein S5 associated with high-level induced spectinomycin resistance.

Twenty-three isolates of Pasteurella multocida were tested for susceptibility to six aminoglycoside agents and screened by polymerase chain reaction for the presence of aminoglycoside resistance genes. In addition, mutations in the resistance-determining region of strains showing a high level of induced resistance to spectinomycin strains were examined. Susceptibility testing showed that all of the isolates were resistant to at least two types of aminoglycosides, and that the most effective antimicrobial was spectinomycin. The resistance genes aphA1, strB and aacA4 were present in all 23 isolates. In the three induced spectinomycin-resistant strains, a 9-bp deletion in rpsE that encodes ribosomal protein S5 was detected.

New Horizons in Mycoplasma genitalium Treatment.

Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human disease has been hampered by its slow growth in culture, difficulty in isolating it, and lack of commercial molecular-based tests for rapid detection. Comparatively few in vitro data on antimicrobial susceptibility are available due to the scarcity of clinical isolates and difficulty in performing susceptibility tests to determine minimum inhibitory concentrations for M. genitalium. Antimicrobial agents that inhibit protein synthesis such as macrolides, along with fluoroquinolones that inhibit DNA replication, have been the treatments of choice for M. genitalium infections. Even though international guidelines recommend azithromycin as first-line treatment, rapid spread of macrolide resistance as well as emergence of quinolone resistance has occurred. Increasing rates of treatment failure have resulted in an urgent need for new therapies and renewed interest in other classes such as aminocyclitols, phenicols, and streptogramins as treatment alternatives. Limited data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin. However, agents with completely new targets and/or mechanisms that would be less likely to show cross-resistance with currently available drugs may hold the greatest promise. Lefamulin, a pleuromutilin, and new nonquinolone topoisomerase inhibitors are attractive possibilities that require further investigation.

Patterns and predictors of antimicrobial resistance among Staphylococcus spp. from canine clinical cases presented at a veterinary academic hospital in South Africa.

BACKGROUND: Antimicrobial resistance in staphylococci, often associated with treatment failure, is increasingly reported in veterinary medicine. The aim of this study was to investigate patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolates from canine samples submitted to the bacteriology laboratory at the University of Pretoria academic veterinary hospital between 2007 and 2012. Retrospective data of 334 Staphylococcus isolates were used to calculate the proportion of samples resistant to 15 antimicrobial agents. The Cochran-Armitage trend test was used to investigate temporal trends and logistic regression models were used to investigate predictors of antimicrobial resistance in Staphylococcus aureus and Staphylococcus pseudintermedius. RESULTS: Results show that 98.2% (55/56) of the S. aureus isolates were resistant to at least one drug while 42.9% were multidrug resistant. Seventy-seven percent (214/278) of the S. pseudintermedius isolates were resistant to at least one drug and 25.9% (72/278) were multidrug resistant. Resistance to lincospectin was more common among S. aureus (64.3%) than S. pseudintermedius (38.9%). Similarly, resistance to clindamycin was higher in S. aureus (51.8%) than S. pseudintermedius (31.7%) isolates. There was a significant (p = 0.005) increase in S. aureus resistance to enrofloxacin over the study period. Similarly, S. pseudintermedius exhibited significant increasing temporal trend in resistance to trimethoprim-sulphamethoxazole (p = 0.004), clindamycin (p = 0.022) and orbifloxacin (p = 0.042). However, there was a significant decreasing temporal trend in the proportion of isolates resistant to doxycycline (p = 0.041), tylosin (p = 0.008), kanamycin (p = 0.017) and amoxicillin/clavulanic acid (p = 0.032). CONCLUSIONS: High levels of multidrug resistance and the increasing levels of resistance to sulphonamides, lincosamides and fluoroquinolones among Staphylococcus spp. isolates in this study are concerning. Future studies will need to investigate local drivers of antimicrobial resistance to better guide control efforts to address the problem.

Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models.

Objectives: New drug regimens employing combinations of existing and experimental antimicrobial agents are needed to shorten treatment of tuberculosis (TB) in humans. The spectinamides are narrow-spectrum semisynthetic analogues of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead 1599, have been previously shown to exhibit a promising therapeutic profile in mice as single agents. Here we explore the in vivo activity of lead spectinamides when combined with other agents. Methods: The efficacy of 1599 or 1810 was tested in combination in three increasingly advanced TB mouse models. Mice were infected by aerosol and allowed to establish acute or chronic infection, followed by treatment (≤4 weeks) with the spectinamides alone or in two- and three-drug combination regimens with existing and novel therapeutic agents. Bacteria were enumerated from lungs by plating for cfu. Results: Herein we show the following: (i) 1599 exhibits additive or synergistic activity with most of the first-line agents; (ii) 1599 in combination with rifampicin and pyrazinamide or with bedaquiline and pyrazinamide promotes significantly improved efficacy in the high-dose aerosol model; (iii) 1599 enhances efficacy of rifampicin or pyrazinamide in chronically infected BALB/c mice; and (iv) 1599 is synergistic when administered in combination with rifampicin and pyrazinamide in the C3HeB/FeJ mouse model showing caseous necrotic pulmonary lesions. Conclusions: Spectinamides were effective partner agents for multiple anti-TB agents including bedaquiline, rifampicin and pyrazinamide. None of these in vivo synergistic interactions was predicted from in vitro MIC chequerboard assays. These data support further development of the spectinamides as combination partners with existing and experimental anti-TB agents.

Factors Associated With Primary Care Physician Knowledge of the Recommended Regimen for Treating Gonorrhea.

BACKGROUND: The recommended regimen for treating uncomplicated gonorrhea has changed over time, due to the emergence of antimicrobial resistance. We assessed physician knowledge of the recommendation for treating uncomplicated urogenital gonorrhea in adolescents and adults using ceftriaxone and azithromycin dual therapy. METHODS: We analyzed DocStyles 2015 survey data from 1357 primary care physicians practicing for at least 3 years who provided screening, diagnosis, or treatment for sexually transmitted diseases to one or more patients in an average month. Logistic regression and χ analyses were used to identify factors associated with knowledge of dual therapy. RESULTS: Among the options of treatment with ceftriaxone alone, azithromycin alone, both of these, or spectinomycin plus levofloxacin, 64% of physicians correctly preferred ceftriaxone plus azithromycin. Knowledge of the recommended dual therapy decreased with increasing years of practice, ranging from 74% among physicians with 3-9 years of practice to 57% among those practicing for ≥24 years (adjusted odds ratio, ORa, for ≥24 vs 3-9 years of practice, 0.50; 95% confidence interval [CI], 0.35-0.70). Knowledge of dual therapy decreased with higher socioeconomic status of patients (ORa for high income vs poor/lower middle income patients, 0.47; 95% CI, 0.32-0.69). Physicians who pursued continuing medical education using journals, podcasts, and government health agencies were more likely to report dual therapy than those who did not use these sources (ORa, 2.09; 95% CI, 1.31-3.33). CONCLUSIONS: Knowledge of the recommended regimen for treating gonorrhea decreased with increasing years of practice and with higher socioeconomic status of patients.