A microbiologic confirmatory test of cure is not needed for persons with a diagnosis of uncomplicated urogenital or rectal gonorrhea who are treated with any of the recommended or alternative regimens; however, anyone with pharyngeal gonorrhea who is treated with an alternative regimen should return 14 days after treatment for a test of cure using culture or a nucleic acid amplification test (NAAT). If the HAT is positive, a confirmatory culture should be attempted prior to retreatment. Antimicrobial susceptibility testing should be performed on all positive cultures. Symptoms that persist after treatment should be evaluated by culture for N. gonorrhoeae (with or without concurrent TAAN), and any gonococcal isolates should be tested to identify antimicrobial susceptibility (modified from Sexually Transmitted Diseases Treatment Guidelines, 2015).

A 34-year-old man consults the emergency department for dysuria and burning in the urethral meatus, with the presence of a thick, whitish discharge coming out through the meatus for the past three days. Which of the following answers is false?

A sample of urethral exudate should be obtained to make the etiological diagnosis.

Empirical treatment with intramuscular ceftriaxone and oral azithromycin in single doses, pending microbiological results.

Antibiogram should be performed in cases where gonorrhoeae is isolated.

2-3 weeks after treatment, new urethral samples should be obtained to confirm microbiological cure.

Haemophilus Species Isolated in Urethral Exudates as a Possible Causative Agent in Acute Urethritis: A Study of 38 Cases.

The incidence of urethritis due to Haemophilus species is increasing. The main aim of this study was to describe the clinical and microbiological characteristics of patients with this form of urethritis. A secondary aim was to discuss the adequacy of treatments in patients with different types of antibiotic resistance. We studied patients with a microbiologically confirmed diagnosis of urethritis seen at the Sexually Transmitted Infections Unit of our hospital between July 2015 and July 2018. We selected all patients in whom Haemophilus species were isolated on chocolate agar. Antibiotic resistance was tested using the disk-diffusion method. Cross-sectional data were collected prospectively during outpatient visits. Haemophilus species were isolated in 33.6% of cases. The most common clinical manifestation was urethral discharge (57.6%); 60% of the patients were men who have sex with men and in this subgroup Haemophilus species were significantly more common than either Neisseria or Chlamydia species. Haemophilus species were found in isolation in 39.5% of patients and the most common one was Haemophilus parainfluenzae (isolated in 84.2% of cases). In total, 34.2% of patients were resistant to azithromycin and 26.3% were resistant to both azithromycin and tetracycline. Empirical treatment achieved clinical and microbiologic cure in 11 of the patients who were not lost to follow-up (n=17; 44.7%). The remaining 6 patients required treatment with a new antibiotic. Haemophilus species are a new cause of nongonococcal urethritis, whose incidence is rising, particularly in men who have sex with men who engage in unprotected oral sex. The clinical manifestations are similar to those seen in gonococcal urethritis. Eradication of infection must be confirmed due to the high rate of antibiotic resistance associated with Haemophilus species.

Management of Urethritis: Is It Still the Time for Empirical Antibiotic Treatments?

Urethritis prevalence in Europe changed in the last years due to both the increase of migratory streams from North Africa and the more frequent exposition of males to relevant risk factors. Owing to these reasons, urethritis treatment should be optimized by accurate microbiological investigations to avoid the risk of persistence, recurrence, or reinfection. The aim of this systematic review is to optimize the treatments for urethritis and investigate the applicability of nucleic acid amplification test (NAAT) as the primary microbiological investigation. A literature search in Medline, Cochrane, and Google Scholar databases was conducted up to June 2018. Subject headings were selected as follows: Urethritis OR gonococcal urethritis OR non-gonococcal urethritis AND Antibiotics OR Recurrence. A total of 528 abstracts were identified and selected. Finally, 12 full-text articles were selected for a qualitative synthesis. The Preferred Reported Items for Systematic Reviews and Meta-Analyses statement was used to perform an accurate research checklist and report. Empirical treatments are no more recommended, although a broad spectrum of antibiotic therapy may be initiated while awaiting the results from pathogens' microbiological characterization. First-line treatment for gonococcal urethritis consists of a single dose of ceftriaxone/azithromycin combined therapy. Specific therapies should be initiated for nongonococcal urethritis according to each single pathogen involved in the infection process. Owing to this reason, NAAT is mandatory in the clinical approach to the disease, although the Gram stain of urethral discharge or smear remains applicable for some less frequent nongonococcal urethritis. Moreover, the urethritis "modern view" also includes noninfectious etiologies that occurred after traumas or injection of irritating compounds. Sexual abstinence of at least 7 d should be observed from the start of treatment to avoid reinfection, while sexual partners should evenly be treated. The treatment of urethritis implies accurate determination of pathogens involved in the infection process by NAAT with subsequent appropriate antibiotic therapy, thus avoiding the risk of antibiotic resistance and overuse of antibiotics indicated for empirical treatments. The population exposed to relevant risk factors should be adequately informed about the increased risk of developing infections and motivated toward the intensive use of condoms during sexual intercourses. Urethritis is a sexually transmitted disease generally characterized by urethral discharge or other symptoms such as itching, tingling, and apparent difficulties in having a regular urinary flow. Microbiological investigations are mandatory to obtain satisfactory results from the treatment. Multiple antibiotic treatments are often necessary due to the high risk of multiple pathogens responsible for the disease. Similarly, sexual partners should be investigated and treated in the same way. Several risk factors such as immunodeficiency, multiple sexual partners, homo- and bisexuality, and alcohol abuse may be related to the disease. In these cases, the use of condom is strongly recommended.

Effective treatment of urethritis. A practical guide.

Most cases of urethritis can be readily treated using recommended regimens. The most important causes of urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae, and initial treatment is directed at them. Optimal management requires obtaining a thorough sexual history, evaluation for objective clinical and laboratory evidence of infection, antimicrobial therapy directed towards the major aetiologies, and evaluation and treatment of sexual partners. Treatment of gonorrhoea requires a single-dose regimen active against N. gonorrhoeae, plus a regimen active against C. trachomatis and nongonococcal urethritis. The usually recommended treatment for N. gonorrhoeae is a single dose of ceftriaxone 250mg intramuscularly, but there are many alternatives, including oral ones. Only in very restricted geographical areas and under restricted situations are penicillins still reliable against N. gonorrhoeae. Recommended optimal treatment of C. trachomatis or nongonococcal urethritis currently requires 7 days' treatment with a tetracycline. Some guidelines now propose ofloxacin 300 mg orally twice daily for 7 days as an equivalent alternative, and there are very promising data with a single dose therapy with azithromycin, a long-acting macrolide antimicrobial. Using recommended regimens, microbiological failure is infrequent in compliant patients. Recurrent urethritis is, however, frequent. For patients who receive recommended treatment and do well, no follow-up cultures are needed. Patients with persistent or recurrent symptoms require careful re-evaluation of the patient, documentation of urethritis, and retreatment with antimicrobial agents a second time if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leucocytes in urethral secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Mycoplasma genitalium: a mycoplasma still underestimated.

Three men referred to the emergency department with suspected sexually transmitted infection like urethritis. After collection of several clinical specimens, they are sent home with a probabilistic treatment. Mycoplasma genitalium research is performed in first line, as Neisseria gonorrhoeae and Chlamydia trachomatis, and comes back positive. Patients are recalled in order to evaluate probabilistic treatment efficiency. M. genitalium, still underestimated because of its recent discovery, is responsible for 10 to 35% of non gonococcal acute and chronical urethritis. Its research is performed by PCR from urogenital specimens like genital swab or first void urine. Until recently, M. genitalium treatment included azithromycin 1g, antibiotic recommended in association with ceftriaxone in the probabilistic treatment of sexually transmitted infections. However, since the discovery of therapeutic failures and the emergence of resistance to azithromycin monodose, azithromycin in extended treatment (500 mg on the first day followed by 250 mg daily during 4 days) is now recommended as first-line agent when M. genitalium is well identified. A control by PCR is expected 4 or 5 weeks after treatment.

Gonorrhoea in men: clinical and diagnostic aspects.

To review the features of gonococcal infection in men in the 1990s. A retrospective study of all men with gonorrhoea presenting to an inner city department of genitourinary medicine in the years 1990 to 1992. 1749 cases of gonorrhoea were seen in 1382 men. A high incidence of gonorrhoea was found in attenders of African or Caribbean extraction. In 228 men with a known date of infection, the incubation period, a mean of 8.3 days, was longer than previously described. The mean infectious period was 12.0 days. By 14 days 86.2% of men had developed symptoms. Of 1615 men with urethral infection 81.9% complained of discharge, while dysuria occurred in 52.8%. Discharge with dysuria were present in only 48.1% of patients. In 10.2% episodes of urethral infection the patients had no symptoms referable to their gonorrhoea. Urethral gonorrhoea was diagnosed by microscopy in 94.4% of symptomatic men and in only 81.1% of asymptomatic men. Microscopy of rectal samples were positive in 46.4% of cases. In this population, a dose of 2 g of ampicillin with 1 g of probenecid gave a high cure rate of gonorrhoea as long as infection was not due to penicillinase-producing organisms. These data suggest that the incubation and infectious period of urethral gonorrhoea has increased compared with previous studies and that symptoms have altered. Only 48.1% of men described the classical symptoms of discharge with dysuria. Microscopy of urethral smears remains useful in symptomatic men but is less sensitive in those without symptoms.

A clinicopathological study of urethritis in males.

To determine the etiology and frequency of different types of urethritis in adult males. A case series. The Dermatology Department of PNS Shifa Hospital, Karachi, from June 2004 to December 2007. One hundred male patients having complaints of urethral discharge and dysuria reporting in the skin OPD were included in the study. Patients who had received systemic treatment for their complaints and those who had other systemic infections were excluded. A detailed history including history of sexual contact was taken. Dermatological examination including examination of external genitalia was also performed. All these patients were subjected to complete physical examination, complete urine examination, urethral pus for gram staining and culture, endo-urethral swab with urethral loop for seeing Chlamydia antigen by fluorescent microscopy, cultures for ureaplasma and Wet mount specimen microscopy for trichomonas along with HIV (serum ELISA) test. Non-gonococcal urethritis was diagnosed on the presence of more than five polymorphonuclear leucocytes per high power field in at least five fields of Gram stained urethral smear, in the absence of Gram negative diplococci. The mean age was 29.2 + or - 5.8 years. Seventy (70%) cases were diagnosed as gonococcal urethritis and 30 (30%) cases as non-gonococcal urethritis (NGU). History of illicit sexual exposure was available in 25 (25%) patients. The interval period between initiation of symptoms and reporting of patient in gonococcal urethritis was 4 to 30 days (mean 12.8 days) and 4 days to 2 months (mean 20.7 days) in non-gonococcal urethritis. The patients with gonococcal urethritis presented with purulent discharge in 66 (84%) cases, and dysuria in 49 (70%) cases. In the NGU group, 25 (80%) cases had mucoid discharge and 18 (65%) had dysuria. in 70%, Neisseria gonorrhoeae was isolated, Chlamydia trachomatis in 16%, ureaplasma in 8%, and Trichomonas vaginalis in 4%. No organism could be detected in 2% cases. HIV test was negative in all cases. Gonococcal urethritis was the commonest urethritis seen followed by Chlamydia infection in the studied group of adult males.

Single dose (direct observed) azithromycin therapy for Neisseria gonorrhoeae and Chlamydia trachomatis in STD clinic attenders with genital discharge in Trinidad and Tobago.

The purpose of this study was to determine the prevalence and to assess the efficacy of a single one gram oral dose of azithromycin under direct observed therapy of genital discharge due to Neisseria gonorrhoeae and Chlamydia trachomatis infections in STD clinic attenders in Trinidad and Tobago. All patients with genital discharge and their contacts were given one gram oral dose of azithromycin under direct supervision after collection of urethral and cervical swabs for N gonorrhoeae culture and smear and for C trachomatis antigen detection by ELISA. Clinical and microbiological evaluation was done on those who returned after 7-10 days for follow-up. Of the 735 patients who were enrolled in the study, 319 (43.4%) had N gonorrhoeae and 100 (13.6%) had C trachomatis. Only 151 (36%) of the 419 patients with a pathogenic isolate returned for clinical and microbiological assessment. The remaining 268 (64%) of the 419 patients were lost to follow-up. One hundred and forty-three patients (94.7%) had total abatement of signs and symptoms after taking azithromycin. One patient (0.65%), who had both N gonorrhoeae and C trachomatis, improved clinically with the drug. Seven patients (six with N gonorrhoeae and one with C trachomatis) failed to respond clinically to azithromycin. Microbiological eradication was achieved in 115 (100%) patients who had single infection with N gonorrhoeae and in 23 patients (96%) with C trachomatis infection. Of 12 patients with combined infections, N gonorrhoeae and C trachomatis were eradicated in 10 and 12 patients, respectively, after initial treatment. In two patients with combined infection, N gonorrhoeae continued to be isolated after treatment with azithromycin. A single one gram oral dose of azithromycin under direct supervision is useful in the treatment of uncomplicated genital infection with N gonorrhoeae and C trachomatis in STD clinic attenders in Trinidad.

Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial.

Azithromycin or doxycycline is recommended for nongonococcal urethritis (NGU); recent evidence suggests their efficacy has declined. We compared azithromycin and doxycycline in men with NGU, hypothesizing that azithromycin was more effective than doxycycline. From January 2007 to July 2011, English-speaking males ≥16 years, attending a sexually transmitted diseases clinic in Seattle, Washington, with NGU (visible urethral discharge or ≥5 polymorphonuclear leukocytes per high-power field [PMNs/HPF]) were eligible for this double-blind, parallel-group superiority trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice daily for 7 days) + placebo azithromycin. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Ureaplasma urealyticum biovar 2 (UU-2), and Trichomonas vaginalis (TV) using nucleic acid amplification tests. Clinical cure (<5 PMNs/HPF with or without urethral symptoms and absence of discharge) and microbiologic cure (negative tests for CT, MG, and/or UU-2) were determined after 3 weeks. Of 606 men, 304 were randomized to azithromycin and 302 to doxycycline; CT, MG, TV, and UU-2 were detected in 24%, 13%, 2%, and 23%, respectively. In modified intent-to-treat analyses, 172 of 216 (80%; 95% confidence interval [CI], 74%-85%) receiving azithromycin and 157 of 206 (76%; 95% CI, 70%-82%) receiving doxycycline experienced clinical cure (P = .40). In pathogen-specific analyses, clinical cure did not differ by arm, nor did microbiologic cure differ for CT (86% vs 90%, P = .56), MG (40% vs 30%, P = .41), or UU-2 (75% vs 70%, P = .50). No unexpected adverse events occurred. Clinical and microbiologic cure rates for NGU were somewhat low and there was no significant difference between azithromycin and doxycycline. Mycoplasma genitalium treatment failure was extremely common. Clinical Trials Registration.NCT00358462.

Urethritis

Individuals displaying persistence or recurrence of symptoms should be instructed for possible re-evaluation. Although there is no standard definition, persistent urethritis is defined as urethritis that has failed to display improvement within the first week of initial therapy. Additionally, recurrent urethritis is defined as urethritis reappearing within 6 weeks after a previous episode of non-gonococcal urethritis. If recurrent symptoms are supported by microscopic evidence of urethritis, then re-treatment is appropriate. The following treatment recommendations are limited and based on clinical experience, expert opinions and guidelines for recurrent or persistent non-gonococcal urethritis: If doxycycline was prescribed as initial therapy, give azithromycin 500 mg or 1 gram for the first day, then give azithromycin 250 mg once daily for 4 days plus metronidazole 400 – 500 mg twice daily for 5 days

Urethra

Infection of the urethra is urethritis, which often causes purulent urethral discharge. It is most often due to a sexually transmitted infection such as gonorrhoea or chlamydia, and less commonly due to other bacteria such as ureaplasma or mycoplasma; trichomonas vaginalis; or the viruses herpes simplex virus and adenovirus. Investigations such as a gram stain of the discharge might reveal the cause; nucleic acid testing based on the first urine sample passed in a day, or a swab of the urethra sent for bacterial culture and sensitivity may also be used. Treatment usually involves antibiotics that treat both gonorrhoea and chlamydia, as these often occur together. A person being treated for urethritis should not have sex until the infection is treated, so that they do not spread the infection to others. Because of this spread, which may occur during an incubation period before a person gets symptoms, there is often contact tracing so that sexual partners of an affected person can be

Randomized controlled clinical trial on the efficacy of fosfomycin trometamol for uncomplicated gonococcal urethritis in men.

We assessed the efficacy of fosfomycin trometamol in treating uncomplicated gonococcal urethritis in men. We conducted an open randomized controlled trial in 152 consecutive men with any main complaints suggestive of uncomplicated gonococcal urethritis in Dujiangyan Medical Center between 1 September 2013 and 31 August 2015. In total, 126 patients completed all aspects of this study. Sixty were provided therapy with fosfomycin trometamol 3 g orally on days 1, 3 and 5 in the intervention group; the other 61 were provided ceftriaxone 250 mg intramuscularly plus azithromycin 1 g orally simultaneously as a single dose in the control group. The primary outcomes involved clinical and microbiologic cure on days 7 and 14 after receipt of all the study medications. At the day 7 follow-up visit, all the 121 participants had complete resolution of clinical symptoms and signs. In addition, five patients (two in the intervention group and three in the control group) discontinued intervention because of unsuccessful treatment. After receipt of all the study medications, these five patients still had urethral purulent discharge and were switched to other unknown treatment regimens by other doctors. The bacterial smears and cultures of urethral or urine specimens in the 121 patients who completed all aspects of the study were negative on a test-of-cure visit. In the per-protocol analysis, both clinical and microbiologic cure were experienced by 96.8% (60/62 patients) in the intervention group and 95.3% (61/64 patients) in the control group. There were no recurrences at the day 14 test-of-cure visit. This trial indicates that fosfomycin trometamol exhibits excellent efficacy for treatment of uncomplicated gonococcal urethritis in men. Serious adverse effects are rare.

Urethritis

A variety of drugs may be prescribed based on the cause of urethritis: Gonococcal urethritis (caused by N. gonorrhoeae): The CDC recommends administering an injection dose of ceftriaxone 250 mg intramuscularly and oral dose of azithromycin 1g simultaneously. Cefixime 400 mg oral single dose can be used as an alternative if ceftriaxone is not available. Non-gonococcal urethritis (caused by Chlamydia trachomatis): The CDC recommends administering an oral single dose of azithromycin 1g or a 7-day course of doxycycline 100 mg orally twice daily.' Alternative treatments can also be used when the above options are not available: Erythromycin base 500 mg orally four times daily for 7 days Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days Levofloxacin 500 mg orally once daily for 7 days Ofloxacin 300 mg orally twice daily for 7 days

Periurethral gland abscess: aetiology and treatment.

To establish some characteristics of patients with periurethral gland abscess, its microbiological profile, and response to treatment. The patients were seen at the Khami Road Clinic, Bulawayo, a municipal STD referral clinic, serving an urban population. Twenty consecutive men with periurethral abscesses were studied. Demographic data and a sexual history were obtained from each patient. Aspirates from the abscess cavities and urethral swabs were collected for microbiology, and blood samples taken for syphilis and HIV serology. The patients were treated by aspiration of the abscess cavities, followed by a single injection of kanamycin 2.0 g followed by a 1 week course of oral doxycycline 100 mg twice daily. Neisseria gonorrhoeae was cultured from three aspirates and five urethral specimens. Chlamydia trachomatis was found in two aspirates and three urethral specimens. Other organisms isolated included Gram negative and anaerobic bacilli. HIV antibody was detected in 13 of 18 patients tested. The response to initial treatment was good, but the abscesses ruptured in two patients, one of whom developed a urinary fistula. One patient required treatment with an alternative antimicrobial regimen. This study demonstrated a role for N gonorrhoeae and possibly for C trachomatis in the aetiology of periurethral abscess. The prevalence of HIV infection in these patients was high. The results of treatment of periurethral abscess by aspiration of pus and followed by antimicrobial therapy covering both N gonorrhoeae and C trachomatis were acceptable.

InternalMed_Harrison

To culture bacterial, fungal, or viral pathogens, an appropriate sample must be placed into the proper medium for growth. The success of efforts to identify a specific pathogen often depends on the collection and transport process coupled to a laboratory-processing algorithm suitable for the specific sample/agent. In some instances, it is better for specimens to be plated at the time of collection rather than first being transported to the laboratory (e.g., urethral swabs being cultured for Neisseria gonorrhoeae). In general, the more rapidly a specimen is plated onto appropriate media, the better the chance is for isolating bacterial pathogens. Deep tissue or fluid (pus) samples are more likely to give useful culture results than are superficial swab specimens. Table 150e-2 lists procedures for collection and transport of common specimens. Because there are many pathogen-specific paradigms for these procedures, it is important to seek advice from the microbiology laboratory when in

InternalMed_Harrison

Evaluate for gonococcal and chlamydial infection. An absence of typical gram-negative diplococci on Gram’s-stained smear of urethral exudate containing inflammatory cells warrants a preliminary diagnosis of NGU, as this test is 98% sensitive for the diagnosis of gonococcal urethral infection. However, an increasing proportion of men with symptoms and/or signs of urethritis are simultaneously assessed for infection with N. gonorrhoeae and C. trachomatis by “multiplex” NAATs of first-voided urine. The urine specimen tested should consist of the first 10–15 mL of the stream, and, if possible, patients should not have voided for the prior 2 h. Culture or NAAT for N. gonorrhoeae may yield positive results when Gram’s staining is negative; certain strains of N. gonorrhoeae can result in negative urethral Gram’s stains in up to 30% of cases of urethral infection. Results of tests for gonococcal and chlamydial infection predict the patient’s prognosis (with greater risk for recurrent NGU if

Management of non-gonococcal urethritis.

Non-gonococcal urethritis (NGU), or inflammation of the urethra, is the most common treatable sexually transmitted syndrome in men, with approximately 20-50 % of cases being due to infection with Chlamydia trachomatis and 10-30 % Mycoplasma genitalium. Other causes are Ureaplasma urealyticum, Trichomonas vaginalis, anaerobes, Herpes simplex virus (HSV) and adenovirus. Up to half of the cases are non-specific. Urethritis is characterized by discharge, dysuria and/or urethral discomfort but may be asymptomatic. The diagnosis of urethritis is confirmed by demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained smear. An excess of mononuclear leucocytes in the smear indicates a viral etiology. In patients presenting with symptoms of urethritis, the diagnosis should be confirmed by microscopy of a stained smear, ruling out gonorrhea. Nucleid acid amplifications tests (NAAT) for Neisseria gonorrhoeae, C. trachomatis and for M. genitalium. If viral or protozoan aetiology is suspected, NAAT for HSV, adenovirus and T. vaginalis, if available. If marked symptoms and urethritis is confirmed, syndromic treatment should be given at the first appointment without waiting for the laboratory results. Treatment options are doxycycline 100 mg x 2 for one week or azithromycin 1 gram single dose or 1,5 gram distributed in five days. However, azithromycin as first line treatment without test of cure for M. genitalium and subsequent Moxifloxacin treatment of macrolide resistant strains will select and increase the macrolide resistant strains in the population. If positive for M. genitalium, test of cure samples should be collected no earlier than three weeks after start of treatment. If positive in test of cure, moxifloxacin 400 mg 7-14 days is indicated. Current partner(s) should be tested and treated with the same regimen. They should abstain from intercourse until both have completed treatment. Persistent or recurrent NGU must be confirmed with microscopy. Reinfection and compliance must be considered. Evidence for the following recommendations is limited, and is based on clinical experience and guidelines. If doxycycline was given as first therapy, azithromycin five days plus metronidazole 4-500 mg twice daily for 5-7 days should be given. If azithromycin was prescribed as first therapy, doxycycline 100 mg x 2 for one week plus metronidazole, or moxifloxacin 400 mg orally once daily for 7-14 days should be given.

[Clinical studies of Chlamydia trachomatis in male urethritis].

From January through December 1986, the urethral smear specimens from 132 male urethritis patients were examined by using Chlamydia trachomatis direct specimen test (Micro Trak). C. trachomatis was detected in 59 (44.7%) out of 132 male urethritis patients, 8 (30.8%) out of 26 patients with gonococcal urethritis (GU), and 51 (48.1%) out of 106 patients with non-gonococcal urethritis (NGU). In 5 (31.3%) out of 16 cases, already treated in other hospitals, infection of C. trachomatis was revealed. The age distribution of the patients with chlamydial urethritis (NGU-C) was between 19 and 52 years old, and the average was 30.9 years old. The peak incubation periods of GU and NGU-C were seen within 7 days and between 8 and 14 days, respectively. In NGU-C patients, 70.6% of them showed WBC less than or equal to 9/hpf in first voided urine sediment. The source of infection was a non-prostitute in 22.2% and a prostitute in 72.2% of GU, while in NGU-C 23.5% was infected from a non-prostitute, and 62.7% from a prostitute. Ofloxacin (OFLX) was administered in a daily dosage of 600 mg (in 3 divided oral doses) for 5 to 14 days in 38 NGU-C patients, and C. trachomatis was eliminated in all cases after the treatment.

[Criteria of recovery from gonorrhea].

A total of 563 case histories of gonorrhea patients and 218 ones of patients with gonorrhea recurrences are analyzed. 86.7-87.5% of recurrences were recorded in the first week after treatment for acute or chronic condition (before the provocation test). The relapses develop earlier after the treatment for acute or subacute gonorrhea than for the chronic condition, and are most common between the third and seventh days after therapy. The share of patients timely consulting the doctors is in inverse proportion with the time of the check-ups (the criterion of cure being 96.2%, the first control 84.1%, the second one 62%). The validity of cure should better be checked up on the fifth-sixth days after therapy, and not on days 7-10. Patients with complicated urogenital diseases (prostatitis, orchiepididymitis, infiltrative urethritis) should be followed up after the first check-up.

When should adenoviral non-gonococcal urethritis be suspected? Two case reports.

The impact of Adenovirus as agent of non-gonococcal urethritis (NGU) is still poorly documented in the literature. We describe two cases showing that adenoviral infection should be reasonably hypothesized in men with dysuria and scant urethral discharge in addition to meatus inflammation and/or edema (meatitis) or conjunctivitis. Case 1: a 55-year-old man came to our observation in July 2012 referring a 5-day-history of intense dysuria and scant mucoid urethral discharge. Physical examination revealed the urethral discharge referred, but also modest meatitis and an intense conjunctival hyperemia on his right eye. Adenoviral infection was investigated and Adenovirus DNA (type 37) was detected in both the urethral and conjunctival swabs. Case 2: a 43-year-old man with intense dysuria, started 4-5 days earlier, came to our attention with his wife in August 2012. Scant urethral mucoid secretions, severe meatal inflammation of the male patient were revealed during physical examination. His wife instead complained of a 2-day history of intense burning eyes. Adenoviral infection was investigated and Adenovirus DNA (type 37) was positive both in the male urethral swab and in his wife's conjunctival swab. Adenovirus seems to cause a distinct and recognisable clinical syndrome in men presenting with urethritis. Studies on the prevalence and role of Adenovirus as a causative agent of urethritis are limited. Moreover, as rapid advanced molecular microbiology is now available, we believe that extending the search to Adenovirus in sexually active men with dysuria, scant discharge in addition to meatitis or conjunctivitis, should be a useful approach improving our understanding about adenoviral NGU, and especially avoiding or stopping unnecessary empirical antibiotic therapy.

Male urethral gonorrhoea -- 5,700 pounds per positive test?

We audited all male urethral gonorrhoea cases from 2003 to determine the additional yield of culture following negative microscopy. Sixty-one episodes were reviewed, of which six were diagnosed by culture alone. In all, 475 cultures were performed to diagnose each case of microscopy-negative infection. As resources in sexual health clinics are limited, it may be appropriate to reconsider our policy of universal male urethral gonococcal culture.

Correlation between In vitro susceptibility and treatment outcome with azithromycin in gonorrhoea: a prospective study.

This prospective study was carried out to determine the antimicrobial susceptibility of Neisseria gonorrhoeae isolates by disc diffusion method and minimum inhibitory concentration (MIC) by E -test with special reference to azithromycin. Also, the correlation between in vitro susceptibility and treatment outcome with single 2 g oral dose azithromycin was assessed. The study included 75 gonococcal isolates from males with urethritis, females with endocervicitis and their sexual contacts. All isolates were subjected to susceptibility testing for penicillin, ciprofloxacin, tetracycline, ceftriaxone, spectinomycin, cefixime and azithromycin. Males with gonococcal urethritis were randomised to receive a single dose of either azithromycin or ceftriaxone. Forty-two men with urethritis received 2 g single oral dose azithromycin, while all other patients were given 250 mg parentral ceftriaxone. All patients were called for follow-up to assess clinical and microbiological cure rates. While all the isolates were susceptible to ceftriaxone, spectinomycin, cefixime and azithromycin; 74 (98.7%), 24 (32%) and 23 (30.7%) strains were resistant to ciprofloxacin, penicillin and tetracycline respectively, by both disc diffusion method and E -test. The MIC range, MIC50 and MIC90 of N. gonorrhoeae strains, to azithromycin were 0.016-0.25, 0.064 and 0.19 microg/mL, respectively. Follow-up attendance of the patients was 52.4 with 100% clinical and microbiological cure rates. Results of our study indicate that 2 g single oral dose azithromycin is safe and effective in the treatment of uncomplicated gonorrhoea.

[Male urethral duplication infection: experience with 9 cases].

To study the clinical characteristics of male urethral duplication infection and offer some guidelines for the diagnosis and treatment of the disease. We analyzed the pathological types, clinical characteristics, therapeutic processes and follow-up results of 9 cases of male urethral duplication. Among the 9 cases of urethral duplication, 7 turned out to be of Type I, 1 Type II A2 and 1 Type II B. The disease courses varied from 2 to 420 days, with an average of 77.2 +/- 141.5 days. Four cases with longer disease duration were identified with a history of repeated use of various antibiotics for treatment. Their clinical manifestations varied, with the outflow of excretions or pus from the duplicate or normal urethra as the cardinal symptoms. The pathogens detected from the secretions were mainly Neisseria gonorrhoeae, Ureaplasma urealyticum, and Chlamydia trachomatis. The consistency rate of the same pathogens detected in the vaginal or cervical secretions from the sex partners of the patients was 87.5%. All the symptoms disappeared after a sufficient-course treatment with sensitive antibiotics, and the patients' sex partners received the same medication simultaneously. No recurrence was found during a 3-month follow-up. Urethral duplication infection has various clinical manifestations, and thus is easily missed in diagnosis. Sufficient-course treatment with sensitive antibiotics is recommended for those that prefer conservative therapy, and their sex partners should be treated simultaneously.

[Various approaches to the length of time of outpatient observation of male patients with gonorrhea].

The authors analyze the findings of clinical and laboratory examinations of 400 male patients with gonorrhea, carried out after the treatment, and correlate these findings with similar data obtained during the clinical diagnosis and therapy. In 288 subjects (62%) three-stage control examinations have yielded favourable results. This fact has called for the development of specific criteria for this patient population; it is suggested that a universal clinical and laboratory examination be carried out in 10-14 days after the treatment. Introduction of a universal reliable criterion of cure for gonorrhea patients will help cut down the periods of post-treatment follow-up.

InternalMed_Harrison

U. urealyticum—but not U. parvum—is associated with NGU. Coliform bacteria can cause urethritis in men who practice insertive anal intercourse. The initial diagnosis of urethritis in men currently includes specific tests only for N. gonorrhoeae and C. trachomatis; it does not yet include testing for Mycoplasma or Ureaplasma species. The following summarizes the approach to the patient with suspected urethritis: 1. Establish the presence of urethritis. If proximal-to-distal “milking” of the urethra does not express a purulent or mucopurulent discharge, even after the patient has not voided for several hours (or preferably overnight), a Gram’s-stained smear of an anterior urethral specimen obtained by passage of a small urethrogenital swab 2–3 cm into the urethra usually reveals ≥5 neutrophils per 1000× field in areas containing cells; in gonococcal infection, such a smear usually reveals gram-negative intracellular diplococci as well. Alternatively, the centrifuged sediment of the

Non-gonococcal urethritis

Nongonococcal urethritis (NGU) is an inflammation of the urethra that is not caused by gonorrheal infection. For treatment purposes, doctors usually classify infectious urethritis in two categories: gonococcal urethritis, caused by gonorrhea, and nongonococcal urethritis (NGU). Symptoms The symptoms of urethritis can include pain or a burning sensation upon urination (dysuria), a white/cloudy discharge and a feeling that one needs to pass urine frequently. For men, the signs and symptoms are discharge from the penis, burning or pain when urinating, itching, irritation, or tenderness. In women, the signs and symptoms are discharge from vagina, burning or pain when urinating, anal or oral infections, abdominal pain, or abnormal vaginal bleeding, which may be an indication that the infection has progressed to Pelvic Inflammatory Disease. NGU is transmitted by touching the mouth, penis, vagina or anus by penis, vagina or anus of a person who has NGU.

A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin.

[Bacteriological finding in the urethra in men with and without non-gonococcal urethritis].

Non-gonococcal urethritis (NGU) is a very common sexually transmitted disease. The etiology of the disease is complex and not completely solved. The aim of this study was to determine the bacteriological finding in the urethra in men with and without non-gonococcal urethritis. The study group comprised 200 men with symptoms of urethritis. The control group consisted of 60 men without symptoms of urethritis. The diagnosis of nongonococcal infection was made by finding of an increased number of polymorphonuclear leukocytes (> or = 5) under the microscope in a sample of Gram-stain of urethral smear (x 1 000) and without evidence of Neisseria. gonorrhoeae in specimens (negative direct microscopy and cell culture). Bacteriological examination included: direct microscopy with the Gram-stained and methylblue-stained smears of urethral discharges, and cultivation of specimens under the aerobic/unaerobic conditions. In addition to standard bacterial examination and performinig direct imunofluorescence test to detect Chlamydia trachomatis (bioMerieux, France), urethral smears were also examined for the presence of Ureaplasma urealyticum and Mycoplasma hominis by commercially available Mycofast Evolution 2 test (International Microbio, France). The finding of mycoplasmas > or = 10(4) CCU/ml was positive. The data were statistically analyzed using Pearson chi2 and Student t test. C. trachomatis was predominant bacterial species found in urethra in men with nongonococcal urethritis. It was isolated alone and/or mixed with mycoplasmas and/or other bacteria in 86 (43.0%) of examinees. There was statistically significant difference in finding of C. trachomatis between the study group and the control group (p < 0.001). U. urealyticum was found in men with NGU: 30.2% were with C. trachomatis and 36.0% were without C. trachomatis (p > 0.05). In 16 (8.0%) men with NGU, C. trachomatis was isolated alone, while in 13.0% examinees it occurred with U. urealyticum. Staphylococcus saprophyticus was isolated in one subject with NGU, alone. Streptococcus agalactiae was found in 1.5% of men with urethritis. Anaerobic bacteria were found in 38 (19.0%) subjects with NGU and in 7 (11.7%) subjects from the control group. C. trachomatis was predominant bacterial species found in urethra in men with nongonococcal urthretitis. Mixed infections were frequent.

Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study.

To evaluate the use of single-dose azithromycin for empirical treatment of nongonococcal urethritis. Randomized, double-blind, multicenter trial comparing azithromycin vs doxycycline therapy, with a 2:1 randomization ratio. Patients were evaluated clinically and microbiologically for Chlamydia trachomatis and Ureaplasma urealyticum infection before therapy and at 2 and 5 weeks after study entry. Eleven sexually transmitted disease clinics throughout the United States. A total of 452 men aged 18 years or older with symptomatic nongonococcal urethritis of less than 14 days' duration. Patients were treated with either 1.0 g of azithromycin as a single oral dose or 100 mg of doxycycline taken orally twice daily for 7 days. Clinical resolution of symptoms and signs of nongonococcal urethritis, microbiological cure of C trachomatis and U urealyticum, and occurrence of adverse experiences. Of the 452 patients enrolled, 248 in the azithromycin-treated group and 123 in the doxycycline-treated group were evaluable for clinical response. The two treatment groups were comparable in terms of age, weight, ethnic distribution, sexual preference, sexual activity, and history of prior nongonococcal urethritis or gonorrhea. Sixteen percent of the azithromycin group and 24% of the doxycycline group were culture positive for C trachomatis before therapy, while 38% and 28%, respectively, were culture positive for U urealyticum. The cumulative clinical cure rate was 81% (95% confidence interval [CI], 75% to 85%) in the azithromycin-treated group and 77% (95% CI, 69% to 84%) in the doxycycline-treated group. Clinical cure rates in the two groups were also comparable when patients were stratified by presence or absence of infection with C trachomatis or U urealyticum prior to therapy. Among those infected with C trachomatis, overall microbiological cure rates were 83% (95% CI, 65% to 94%) for azithromycin-treated patients (n = 30) and 90% (95% CI, 68% to 98%) for doxycycline-treated patients (n = 21). Among those infected with U urealyticum, overall microbiological cure rates were 45% (95% CI, 34% to 57%) for azithromycin-treated patients (n = 75) and 47% (95% CI, 30% to 65%) for doxycycline-treated patients (n = 32). Adverse reactions were generally mild to moderate and occurred in 23% of the azithromycin-treated group and 29% of the doxycycline-treated group. For empirical treatment of the acute nongonococcal urethritis syndrome in men, a single oral dose of azithromycin was as effective as a standard 7-day course of doxycycline in achieving clinical cure. Further, clinical cure rates were comparable with either regimen, regardless of the presence or absence of Chlamydia or Ureaplasma infection.

[Epidemiologic and therapeutic study on gonorrheal infections--one shot therapy by aztreonam].

A clinical study of a new monocyclic beta-lactam antibiotic, AZTREONAM (hereafter referred to as AZT) for gonorrheal infections as well as epidemiologic study of gonorrheal infections were made Epidemiology: There was a reflection of the increasing sexual activity of the younger generation; both male and female patients in their twenties were most frequent (male 49.5%, female 43.7%) and the percent of teen age patients was 15.1% (male) and 34.4% (female). Forty two strains (17.2%) out of 244 clinically isolated gonococci were PPNG. Residue of serious secretion was observed in a little less than 20% suggesting a complication by Chlamydia trachomatis. Clinical Result: One shot (1-2 g) therapy by AZT was given to 244 gonorrheal infection cases (212 urethritis cases of males. 32 cervicitis cases of females) with the following highly effective rate. Although beta-lactamase producing MIC of AZT at 10(6) CFU/ml showed a peak of 0.025 microgram/ml and ranged between less than 0.0125 microgram/ml to 0.2 microgram/ml. The time required for the elimination of gonococci was studied by the administration of 1 g and 2 g AZT. Gonococci became extinct in 1-8 hours or 4-4.5 hours on average. The difference between n 1 g and 2 g was scarcely observed. Clinical effect of 1 g one shot and 2 g one shot AZT was examined on the 3rd treatment day for 244 male and females cases. The effective rate was high; 90.7% by 1 g, 97.1% by 2 g for male urethritis, 100% by 1 g also by 2 g for female cervicitis. This therapeutic efficacy was kept even in PPNG, isolated cases. There were two side effects (0.8%), one case each of numbness and, redness and swelling of both hands, out of 244 cases, but both of them were minor ones without clinical complication.

Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis.

We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability. We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients. The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3. A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable.

Two gram single dose amoxycillin in treatment of gonococcal and other urethritides.

In a trial of 2 grams oral single dose of amoxycillin on 70 patients with acute gonococcal urethritis, 64 patients had full bacteriological cure, 4 patients were lost to follow up and presumed cured, two patients, still had gonococcal urethritis one week after treatment but one admitted to re-exposure and subsequently recovered with a second 2 gram single dose of "amoxil". Among 30 patients with non gonococcal Urethritis (N.G.U.) treated similarly, a fairly good response was obtained in those patients in whom Staph. Aureas was absent from the urethral discharge. However single dose therapy was considered unsuitable for non gonococcal urethritis.

Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.