Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID) in 10-25%. Transmission of M. genitalium occurs through direct mucosal contact.
UNASSIGNED: Asymptomatic infections are frequent. In men, urethritis, dysuria and discharge predominate. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. Symptoms are the main indication for diagnostic testing. Diagnosis is achievable only through nucleic acid amplification testing and must include investigation for macrolide resistance mutations.
METHODS: Therapy for M .genitalium is indicated if M. genitalium is detected. Doxycycline has a cure rate of 30-40%, but resistance is not increasing. Azithromycin has a cure rate of 85-95% in macrolide-susceptible infections. An extended course of azithromycin appears to have a higher cure rate, and pre-treatment with doxycycline may decrease organism load and the risk of macrolide resistance selection. Moxifloxacin can be used as second-line therapy but resistance is increasing.
UNASSIGNED: Uncomplicated M. genitalium infection without macrolide resistance mutations or resistance testing: Azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral). Second-line treatment and treatment for uncomplicated macrolide-resistant M. genitalium infection: Moxifloxacin 400 mg od for 7 days (oral). Third-line treatment for persistent M. genitalium infection after azithromycin and moxifloxacin: Doxycycline or minocycline 100 mg bid for 14 days (oral) may cure 40-70%. Pristinamycin 1 g qid for 10 days (oral) has a cure rate of around 75%. Complicated M. genitalium infection (PID, epididymitis): Moxifloxacin 400 mg od for 14 days. MAIN CHANGES FROM THE 2016 EUROPEAN M.
UNASSIGNED: Due to increasing antimicrobial resistance and warnings against moxifloxacin use, indications for testing and treatment have been narrowed to primarily involve symptomatic patients. The importance of macrolide resistance-guided therapy is emphasised.

New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects.

Mycoplasma genitalium is frequently associated with urogenital and rectal infections, with the number of cases of macrolide-resistant and quinolone-resistant M. genitalium infection continuing to increase. In this study, we examined the levels of resistance to these two common antibiotic treatments in geographically distinct locations in Queensland, Australia. Samples were screened for macrolide resistance-associated mutations using a commercially available kit (ResistancePlus MG; SpeeDx), and quinolone resistance-associated mutations were identified by PCR and DNA sequencing. Comparisons between antibiotic resistance mutations and location/gender were performed. The levels of M. genitalium macrolide resistance were high across both locations (62%). Quinolone resistance mutations were found in ∼10% of all samples, with a number of samples harboring mutations conferring resistance to both macrolides and quinolones. Quinolone resistance was higher in southeast Queensland than in north Queensland, and this was consistent in both males and females (P = 0.007). The M. genitalium isolates in rectal swab samples from males harbored high levels of macrolide (75.9%) and quinolone (19%) resistance, with 15.5% harboring resistance to both classes of antibiotics. Overall, the lowest observed level of resistance was to quinolones in females from north Queensland (1.6%). These data highlight the high levels of antibiotic resistance in M. genitalium isolates within Queensland and the challenges faced by sexually transmitted infection clinicians in managing these infections. The data do, however, show that the levels of antibiotic resistance may differ between populations within the same state, which has implications for clinical management and treatment guidelines. These findings also support the need for ongoing antibiotic resistance surveillance and tailored treatment.

To describe a new grading system and associated treatment guidelines for the acute ocular manifestations of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Prospective case series.
Seventy-nine consecutive patients (158 eyes) evaluated and treated for acute ocular involvement in SJS or TEN during hospitalization.
Photographic and chart review of acute ocular findings, interventions received, and outcomes with regard to visual acuity, dry eye symptoms, and scarring sequelae at least 3 months after the acute illness.
Visual acuity, dry eye severity, and scarring of the ocular surface and eyelids were assessed after follow-up of at least 3 months.
Cases graded as mild or moderate were managed medically. All had best-corrected visual acuity (BCVA) of 20/20, no dry eye symptoms, and no scarring sequelae. Cases graded as severe or extremely severe were treated with urgent amniotic membrane transplantation (AMT) in addition to medical management. Severe cases all had BCVA of 20/20 and mild or no dry eye problems. Five of 28 patients had mild tarsal conjunctival scarring. No other scarring sequelae occurred. Nine of the 10 extremely severe cases had BCVA of 20/20 (1 was 20/30). Three of 10 had moderate scarring of the tarsal conjunctiva and lid margins and also moderate dry eyes with severe photophobia. Seven of 10 had only mild or no dry eye symptoms and scarring sequelae.
This grading system facilitates decision making in the evaluation and management of the acute ocular manifestations of SJS and TEN. Mild and moderate cases have a low risk of significant scarring or visual sequelae and may be monitored and treated medically if not worsening. Severe and extremely severe cases should receive urgent AMT to decrease the risk of scarring and visual sequelae.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

We present the updated British Association for Sexual Health and HIV guideline for the management of non-gonococcal urethritis in men. This document includes a review of the current literature on its aetiology, diagnosis and management. In particular it highlights the emerging evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium and that neither azithromycin 1 g nor doxycycline 100 mg twice daily for seven days achieves a cure rate of >90% for this micro-organism. Evidence-based diagnostic and management strategies for men presenting with symptoms suggestive of urethritis, those confirmed to have non-gonococcal urethritis and those with persistent symptoms following first-line treatment are detailed.

Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods.

OBJECTIVE: In an era of limited resources, policy makers and health care payers are concerned about the costs of treatment in addition to its effectiveness. However, guidelines do not tend to consider the cost-effectiveness of treatment options. This paper aims to conduct an international literature review with a view to assessing the impact of pharmaco-economic considerations of CAP treatment with moxifloxacin on recent guidelines.
METHODS: The pharmaco-economic state of the art of treating CAP with moxifloxacin is assessed and compared with guidelines issued by the European Respiratory Society and by the Infectious Diseases Society of America/American Thoracic Society. Also, evidence on moxifloxacin consumption and antimicrobial resistance, and the impact of resistance on the cost-effectiveness of moxifloxacin is reviewed. Studies were identified by searching PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, and EconLit up to January 2009.
RESULTS: The existing pharmaco-economic evidence indicates that moxifloxacin is a cost-effective treatment for CAP. However, data limitations and uncertainty surrounding the evolution of resistance emphasize the need for caution. As recommended by guidelines, the choice of antimicrobial should consider the local frequency of causative pathogens, the local pattern of antimicrobial resistance, and risk factors for resistant bacteria. The pharmaco-economic evidence corroborates the importance of these factors as they have an impact on the cost-effectiveness of treating CAP patients with moxifloxacin.
CONCLUSIONS: CAP guidelines need to take into account pharmaco-economic considerations by balancing the effectiveness of antimicrobial regimens against their costs. The pharmaco-economic value of moxifloxacin is influenced by the causative pathogens involved and resistance patterns. Therefore, it may be advisable to identify patient subgroups in which treatment with moxifloxacin is cost-effective and should be recommended by guidelines.

A summary of the key data presented to Clinical and Laboratory Standards Institute (CLSI, formerly National Committee for Clinical and Laboratory Standards) in determination of moxifloxacin anaerobic breakpoints is presented. The breakpoint analysis required review of a variety of data, including bacteriologic and clinical outcomes by MIC of anaerobic isolates from prospective clinical trials in patients with complicated intra-abdominal infections, human and animal pharmacokinetic/pharmacodynamic (PK/PD) information and in vitro models, MIC distributions of indicated organisms, and animal model efficacy data for strains with MIC values around prospective breakpoints. The compilation of the various components of this breakpoint analysis supports the US Food and Drug Administration (FDA) and CLSI moxifloxacin anaerobic breakpoints of < or =2 mg/L (susceptible), 4 mg/L (intermediate), and > or =8 mg/L (resistant), and provides information to European investigators for interpretation of MICs prior to establishment of the European Committee on Antimicrobial Susceptibility Testing breakpoints.