Ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic hepatitis C and bleeding disorders.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is prevalent among patients with inherited bleeding disorders and is a leading cause of mortality in those with haemophilia. AIM: We evaluated the efficacy and safety of ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic HCV genotype 1-4 infection and an inherited bleeding disorder. METHODS: Ledipasvir-sofosbuvir was administered for 12 weeks to patients with genotype 1 or 4 infection and for 12 or 24 weeks to treatment-experienced cirrhotic patients with genotype 1 infection. Patients with genotype 2 and 3 infection received sofosbuvir plus ribavirin for 12 and 24 weeks respectively. RESULTS: The majority of the 120 treated patients had a severe bleeding disorder (55%); overall, 65% of patients had haemophilia A and 26% of patients had haemophilia B; 22% were HIV coinfected. Sustained virologic response at 12 weeks posttreatment was 99% (98/99) in patients with genotype 1 or 4 infection; 100% (5/5) in treatment-experienced cirrhotic patients with genotype 1 infection; 100% (10/10) in patients with genotype 2 infection; and 83% (5/6) in patients with genotype 3 infection. There were no treatment discontinuations due to adverse events (AEs). The most frequent non-bleeding AEs were fatigue, headache, diarrhoea, nausea and insomnia. Bleeding AEs occurred in 22 patients, of which all but one were considered unrelated to treatment. CONCLUSION: Treatment with ledipasvir-sofosbuvir for patients with HCV genotype 1 or 4 infection or sofosbuvir plus ribavirin for patients with genotype 2 or 3 infection was highly effective and well tolerated among those with inherited bleeding disorders.

Examining self and partners for syphilis among men who have sex with men: five US cities, 2009-2011.

To increase self-examination for syphilis among men who have sex with men (MSM), we developed educational materials to increase knowledge of primary and secondary syphilis manifestations. Materials were piloted in five cities' infectious disease or MSM clinics. Self- and partner-examination behaviour was assessed with an anonymous questionnaire. Of 1459 participants, 914 men had had sex with a man in the previous three months; the 171 MSM who reported having read the materials were significantly more likely to examine themselves (anus, adjusted prevalence ratio [aPR] 1.3, 95% confidence interval [CI] 1.15-1.52), mouth, penis and skin, and their partners' anus (aPR 1.3, 95% CI 1.03-1.73) and mouth (aPR 1.6, 95% CI 1.1-2.26). Further research is needed to determine whether educational materials affect early detection and treatment of primary and secondary syphilis and reduce transmission.

Self-reported syphilis and gonorrhoea testing among men who have sex with men: national HIV behavioural surveillance system, 2003-5.

OBJECTIVES: The Centers for Disease Control and Prevention provides guidance on sexually transmitted disease (STD) testing specifically for men who have sex with men (MSM) in STD treatment guidelines to address increasing rates of gonorrhoea and syphilis among MSM in the USA. The guidelines recommend at least annual syphilis, gonorrhoea and chlamydia testing for sexually active MSM. The implementation of these guidelines was evaluated. METHODS: Data from the 2003-5 MSM cycle of the National HIV Behavioural Surveillance System were used. The proportion of sexually active HIV-negative MSM reporting syphilis and gonorrhoea testing during the previous year was determined and multivariate logistic regression was used to identify factors associated with testing. RESULTS: Of 10 030 MSM, 39% and 36% reported having been tested for syphilis and gonorrhoea in the previous year, respectively. Four factors were associated with syphilis and gonorrhoea testing, respectively: age 18-24 years versus > or =45 years (odds ratio (OR) 2.2, 95% CI 1.8 to 2.5; OR 2.7, 95% CI 2.3 to 3.2), black versus white race (OR 1.3, 95% CI 1.1 to 1.4; OR 1.4, 95% CI 1.2 to 1.6), private insurance versus no insurance (OR 1.3, 95% CI 1.1 to 1.4; OR 1.3, 95% CI 1.1 to 1.4) and disclosing male-male sex to a healthcare provider (OR 2.2, 95% CI 2.0 to 2.5; OR 2.1, 95% CI 1.9 to 2.3). CONCLUSIONS: Syphilis and gonorrhoea testing among MSM was low, despite specific testing recommendations in the STD treatment guidelines. To increase STD testing among MSM, healthcare providers should assess the risks of STD for male patients through routine enquiries about sexual activity.

Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure.

In vitro susceptibility testing and genotyping were done on urogenital isolates of Chlamydia trachomatis from 3 patients, 2 of whom showed evidence of clinical treatment failure with azithromycin and one of whom was the wife of a patient. All 3 isolates demonstrated multidrug resistance to doxycycline, azithromycin, and ofloxacin at concentrations >4.0 microg/mL. Recurrent disease due to relapsing infection with the same resistant isolate was documented on the basis of identical genotypes of both organisms. This first report of clinically significant multidrug-resistant C. trachomatis causing relapsing or persistent infection may portend an emerging problem to clinicians and public health officials.

Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases.

In preparing the 1998 sexually transmitted disease treatment guidelines of the Centers for Disease Control and Prevention, we reviewed evidence regarding the need to eradicate anaerobes when treating pelvic inflammatory disease (PID). Anaerobes are present in the upper genital tract during an episode of acute PID, with the prevalence dependent on the population under study. Vaginal anaerobes can facilitate acquisition of PID and cause tissue damage to the fallopian tube, either directly or indirectly through the host inflammatory response. Use of several broad-spectrum regimens appears to result in excellent clinical cure rates, despite the fact that some combinations fall short of providing comprehensive coverage of anaerobes. There are limited data on the long-term effects of failing to eradicate anaerobes from the upper genital tract. Concern that tissue damage may continue when anaerobes are suboptimally treated has prompted many experts to caution that therapeutic regimens should include comprehensive anaerobic coverage for optimal treatment of women with PID.

Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis.

The genus Scedosporium contains two medically significant species of emerging mycotic agents, S. apiospermum and S. prolificans, which have received scant attention. Scedosporium apiospermum is the anamorph, or asexual state, of the cosmopolitan fungus Pseudallescheria boydii, with both sharing the same risk factors for infection, clinical spectrum, and histopathologic features. Scedosporium prolificans is a recently recognized agent of bone, soft tissue, and joint infections that occurs with highest frequency in children and young adults. S. prolificans may also cause potentially fatal disseminated infections in immunocompromised persons. The drug sensitivities of both Scedosporium species are significantly different from those of most other fungi, and thus identification of these organisms is important. Unfortunately, the pathological features of Scedosporium infections may be easily confused with other mycotic agents, resulting in delayed or inappropriate medical therapy. Because many pathologists and clinicians are unfamiliar with the significance of Scedosporium spp. infection, this communication describes three persons with differing clinical and pathological presentations of S. apiospermum infection. In one patient with sickle cell disease and chronic mycotic sinusitis, fungal colonies of S. apiospermum removed from the sinuses showed a pattern of alternating zones of mycelial hypercellularity and hypocellularity associated with conidiation, similar to a previous report of P. boydii infection. The clinicopathologic features of an immunocompetent person with S. apiospermum osteomyelitis, and a patient with S. apiospermum infection of the brain after bone marrow transplantation, are also described.

Musculoskeletal infections in patients with human immunodeficiency virus infection.

Musculoskeletal infections constitute an unusual clinical manifestation in patients with human immunodeficiency virus (HIV) infection. Available information about patients' characteristics and their clinical course has been obtained mainly from case reports and small retrospective studies. Our retrospective study is the largest in the literature providing detailed information about the clinical and laboratory characteristics of HIV-infected patients with different musculoskeletal infections. We identified 30 patients with various infections of the musculoskeletal system during a 5-year period among a cohort of 3,000-4,000 HIV-infected patients, and we describe them along with all cases of musculoskeletal infections in patients with HIV reported in the literature since 1985. Septic arthritis was the most commonly reported infection of the musculoskeletal system. It usually affects young men with a median CD4 count of 241. The exact contribution of a previous history of intravenous drug abuse in the pathogenesis of septic arthritis is unclear from the present and previous studies. Staphylococcus aureus was the most commonly isolated agent (31.3%). Numerous atypical pathogens were also identified as causes of septic arthritis. Approximately 90% of patients recovered with appropriate antibiotic treatment. Osteomyelitis was a more serious infection which also affected young individuals but with lower CD4 counts (median, 41). Half the cases were due to atypical mycobacteria. The mortality rate in the previously reported cases and in our series was high (20%). Pyomyositis is an increasingly recognized infection of the striated muscles in HIV-infected patients. It affects almost exclusively males with advanced HIV infection (median CD4 count, 24). Most cases are due to Staphylococcus aureus (67%). Drainage of the involved muscle(s) accompanied by proper antibiotic treatment resulted in resolution of the infection in the majority of patients (90%). Although the incidence of musculoskeletal infections in patients with HIV from this and previous studies appears to be low (0.3%-3.5%), these infections add a significant morbidity and mortality in the affected individuals. Better understanding of their pathogenesis and clinical course would aid the proper diagnosis and management of these infections.

Enterococcal arthritis: case report and review.

We report a case of septic arthritis due to Enterococcus species and review 18 additional cases reported in the literature from 1966 through 1993 for which clinical or treatment data were available. In 11 of the 19 cases, prosthetic joints were affected (9 knees, 2 hips) and in 8 cases, native joints were affected. Of those patients with prosthetic joint infections, 6 had preexisting osteoarthritis and 3 had rheumatoid arthritis; only one patient with native joint infection had a recognized (although unspecified), preexisting joint abnormality. Pain, fever (temperature, > 37 degrees C), and tenderness were the most common clinical findings in patients with native joint infections. The microbiological diagnosis was made by culture of synovial fluid or synovial tissue (16 of 19), blood (1 of 19), or an unstated specimen (2 of 19). Polymicrobial infection was present in 6 (32%) of 19 patients. Of fourteen patients treated with either a parenteral penicillin (11 of 19) or a glycopeptide (3 of 19), 11 made an uncomplicated recovery. An aminoglycoside was also used to treat 7 of these 14 patients (4 of these 7 had prosthetic joints). All 11 prosthetic joint infections were ultimately clinically cured; for most of these patients, the original prosthesis was removed. For two patients with native joint infections, amputation of the infected limb was necessary to cure the infection.

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

OBJECTIVE: To evaluate the use of single-dose azithromycin for empirical treatment of nongonococcal urethritis. DESIGN: 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. SETTING: Eleven sexually transmitted disease clinics throughout the United States. PATIENTS: A total of 452 men aged 18 years or older with symptomatic nongonococcal urethritis of less than 14 days' duration. INTERVENTION: 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. MAIN OUTCOME MEASURES: Clinical resolution of symptoms and signs of nongonococcal urethritis, microbiological cure of C trachomatis and U urealyticum, and occurrence of adverse experiences. RESULTS: 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. CONCLUSIONS: 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.

Clinical manifestations of genital infection due to Chlamydia trachomatis in women: differences related to serovar.

The relationship between the infecting Chlamydia trachomatis serovar and the clinical manifestations of genital tract infection was evaluated in a study of 155 women attending a sexually transmitted diseases clinic; 99 women had lower genital tract infection and 56 had Chlamydia-associated pelvic inflammatory disease (PID). In the group with lower genital tract infection, women with serovar F differed from those with serovars of class B or C in that they exhibited fewer signs of cervical infection, including easily induced bleeding (P = .04), edema of the zone of cervical ectopy (P = .06), and colposcopic evidence of mucopurulent endocervical discharge (P = .007). Serovar F also produced fewer infections with inclusion counts of > or = 1,000 and fewer rectal infections (P = .04). There was no apparent association of any specific serovar with PID. Thus, in this population, serovar F was associated with fewer objective clinical manifestations of mucopurulent endocervical discharge, and the distribution of chlamydial serovars found in PID reflected that found in lower genital tract infection.

Long-term eradication of Chlamydia trachomatis genital infection after antimicrobial therapy. Evidence against persistent infection.

OBJECTIVE: To determine whether Chlamydia trachomatis urogenital infections persist or relapse after antimicrobial therapy by serial measurement of chlamydial-specific DNA using the polymerase chain reaction (PCR), cell cultures, and serological studies. DESIGN: Prospective evaluation of an inception cohort. SETTING: University student health clinic. PARTICIPANTS: Twenty women with culture-proven and PCR-proven C trachomatis urogenital infections. MEASUREMENTS: Incidence of persistent infection as determined by PCR, culture, and serial measurement of local and systemic antibody to C trachomatis for 5 months after doxycycline therapy. RESULTS: Prior to therapy, C trachomatis was isolated in cell culture from the cervix in 19 of 20 women, from the urethra in 13 women, and from the rectum in 13 women. All culture-positive specimens were also PCR-positive. Immediately after completion of antimicrobial therapy, all women had negative cell cultures for chlamydia. Ten of 20 culture-negative cervical specimens and two culture-negative urethral specimens had chlamydial DNA present immediately after treatment. In addition, three women had detectable DNA from cervical specimens 1 week after treatment. The presence of cervicitis (P = .01), high inclusion counts (P = .004), and serological evidence of recent infection (P = .0004) were each significantly associated with PCR positivity after treatment. All 384 subsequent cervical, rectal, and urethral specimens collected over 5 months were negative by both PCR and culture with the exception of one woman who was reinfected. Serum immunoglobulin M (IgM) titers, geometric mean serum immunoglobulin G (IgG) titers, and prevalence of local antibody to chlamydia progressively declined after treatment. CONCLUSIONS: Standard antimicrobial therapy is effective in the long-term microbiologic eradication of uncomplicated C trachomatis urogenital infections. The presence of chlamydial DNA after antimicrobial therapy is of short duration and reflects excretion of nonviable organisms rather than persistent infection.

Association of genital infection with specific Chlamydia trachomatis serovars and race.

Black race is an important risk marker for Chlamydia trachomatis genital infection. To define whether C. trachomatis serovars differ by ethnic distribution, a panel of monoclonal antibodies was used to serotype 934 urethral and 581 cervical isolates from patients attending a sexually transmitted diseases clinic over 2 years. The overall serovar distribution in cervical and urethral infections was comparable, with B class serovars predominating. Significantly higher inclusion counts were observed both in younger women and in nonblacks regardless of serovar. Serovar D was less frequent among blacks at the urethral site (P = .001), while serovar Ia was more frequent in blacks at both sites (urethral, P < .001; cervical, P = .02). These associations remained significant after adjusting for age and number of inclusion-forming units by multivariate analysis. Thus, specific serovars may be associated with particular racial groups; either behavioral or biologic factors could explain these findings.

Systemic Bacillus species infection mimicking listeriosis of pregnancy.

Bacillus species are increasingly recognized as agents of infection in humans. These organisms are ubiquitous in nature and can cause clinical illness ranging from transient bacteremia to serious systemic infection. We describe a pregnant intravenous drug abuser with fever, constitutional symptoms, and premature labor. Her blood cultures yielded gram-positive bacilli, and her clinical course was consistent with systemic listeriosis of pregnancy. Pathological examination of the placenta revealed acute villitis, and Bacillus species grew from cultures of both placenta and blood. Through biochemical testing the isolate was identified as Bacillus pumilis. To our knowledge, this is the first reported case of premature labor induced by Bacillus species infection.