Clinical Characteristics of Anorectal Mycoplasma genitalium Infection and Microbial Cure in Men Who Have Sex With Men.

BACKGROUND: We report clinical characteristics of proctitis caused solely by Mycoplasma genitalium (MG) compared with chlamydia and gonococcus. We determined the proportions cured with first-line (azithromycin) and second-line antimicrobials (moxifloxacin, pristinamycin). METHODS: A total of 166 patients attending Melbourne Sexual Health Centre from 2012 to 2016 with symptoms of proctitis were tested for MG, Chlamydia trachomatis, and Neisseria gonorrhoeae. Demographic characteristics, sexual behaviors, clinical symptoms, and signs were recorded. Multinomial multivariable logistic regression was used to test for significant differences in symptoms and signs for the pathogens detected. RESULTS: Seventeen percent of men had MG (95% confidence interval, 12-24), 21% had chlamydia (15-27), and 40% had gonococcal monoinfection (32-48), whereas 22% had MG coinfection (16-29). Relative to men with MG monoinfection, those with chlamydial monoinfection reported more anal pain (adjusted prevalence odds ratio (aPOR), 4.68 [1.41-14.19]), whereas men with gonococcal monoinfection reported more anal pain (aPOR, 6.75 [2.21-20.55]) and tenesmus (aPOR, 15.44 [1.62-146.90]), but less anal itch (aPOR, 0.32 [0.11-0.93]). The microbiological cure for MG using azithromycin was low at 35% (22-50), whereas moxifloxacin subsequently cured 92% (64-100) and pristinamycin cured 79% (54-94) of infections. CONCLUSIONS: M. genitalium was almost as common as chlamydia in men presenting to a sexual health center with symptoms of proctitis. Men with anorectal MG monoinfection were less likely to have symptoms and signs compared with those with chlamydia or gonococcus monoinfection. Cure for men with symptomatic anorectal MG by azithromycin was low. We suggest routine testing for MG in cases of proctitis, with test of cure after treatment being essential.

Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection.

High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.

Pristinamycin in the treatment of MSSA bone and joint infection.

OBJECTIVES: The aim of this study was to evaluate pristinamycin in the treatment of MSSA bone and joint infection (BJI). PATIENTS AND METHODS: A retrospective, single-centre cohort study (2001-11) investigated outcome in adults receiving pristinamycin for MSSA BJI and pristinamycin-related adverse events (AEs). RESULTS: One hundred and two MSSA BJIs were assessed in 98 patients [chronic infection, 33.3%; and orthopaedic device-related infection (ODI), 67.6%]. Surgery was performed in 77.5% of total cases, and in all but three ODIs, associated with antibiotic therapy of a median total duration of 29.2 weeks. Pristinamycin was prescribed as a part of the initial intensive treatment phase (29.4%) and/or included in final maintenance therapy (83.3%) at a dose of 47.6 (45.5-52.6) mg/kg/day for 9.3 (1.4-20.4) weeks. AEs occurred in 13.3% of patients, consisting of gastrointestinal disorder (76.9%) or allergic reaction (23.1%), leading to treatment interruption in 11 cases. AEs were related to daily dose (OR, 2.733 for each 10 additional mg/kg/day; P = 0.049). After a follow-up of 76.4 (29.6-146.9) weeks, the failure rate was 34.3%, associated with ODI (OR, 4.421; P = 0.006), particularly when the implant was retained (OR, 4.217; P = 0.007). In most patients, the pristinamycin companion drug was a fluoroquinolone (68.7%) or rifampicin (21.7%), without difference regarding outcome. CONCLUSIONS: Pristinamycin is an effective, well-tolerated alternative therapeutic option in MSSA BJI, on condition that a daily dosage of 50 mg/kg is respected.

Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens.

BACKGROUND: Our aim was to determine the efficacy of 1 g azithromycin and alternative antibiotic regimens in a prospective cohort of Mycoplasma genitalium-infected participants, and factors associated with azithromycin failure. METHODS: Consecutive eligible M. genitalium-infected men and women attending the Melbourne Sexual Health Centre between July 2012 and June 2013 were treated with 1 g of azithromycin and retested by polymerase chain reaction (PCR) on days 14 and 28. Cure was defined as PCR negative on day 28. Cases failing azithromycin were treated with moxifloxacin, and those failing moxifloxacin were treated with pristinamycin. Pre- and posttreatment samples were assessed for macrolide resistance mutations (MRMs) by high-resolution melt analysis. Mycoplasma genitalium samples from cases failing moxifloxacin were sequenced for fluoroquinolone resistance mutations. Multivariable analysis was used to examine associations with azithromycin failure. RESULTS: Of 155 participants treated with 1 g azithromycin, 95 (61% [95% confidence interval {CI}, 53%-69%]) were cured. Pretreatment MRM was detected in 56 (36% [95% CI, 28%-43%]) participants, and strongly associated with treatment failure (87% [95% CI, 76%-94%]; adjusted odds ratio, 47.0 [95% CI, 17.1-129.0]). All 11 participants who had MRM detected in posttreatment samples failed azithromycin. Moxifloxacin was effective in 53(88% [95% CI, 78%-94%]) of 60 cases failing azithromycin; all failures had gyrA and parC mutations detected in pretreatment samples. Six of 7 patients failing moxifloxacin treatment received pristinamycin, and all were PCR negative 28 days after pristinamycin treatment. CONCLUSIONS: We report a high azithromycin failure rate (39%) in an M. genitalium-infected cohort in association with high levels of pretreatment macrolide resistance. Moxifloxacin failure occurred in 12% of patients who received moxifloxacin; all had pretreatment fluoroquinolone mutations detected. Pristinamycin was highly effective in treating macrolide- and quinolone-resistant strains.

Pristinamycin: old drug, new tricks?

Osteoarticular infections with Gram positive bacteria present an increasing challenge in an era of multidrug-resistant organisms. Prolonged intravenous antibiotic treatment is often required, with associated risks, costs and difficulties with administration; a safe, effective oral option would be ideal for this indication. Pristinamycin, an oral streptogramin antibiotic with bactericidal activity against Gram positive organisms including methicillin-resistant Staphylococcus aureus, has been used for over 50 years in Europe for the treatment of osteoarticular infections. We review the published evidence for the treatment of native bone and prosthesis-related osteoarticular infections with pristinamycin.

Streptogramins - two are better than one!

Streptogramins are potent drugs against numerous highly resistant pathogens and therefore are used as antibiotics of last-resort human therapy. They consist of a mixture of two different types of chemical substances - the group A streptogramins, which are polyunsaturated macrolactones, and the group B streptogramins, representing cyclic hexadepsipeptides. Streptogramins are unique in their mode of action: each component alone exhibits a moderate bacteriostatic activity by binding to the bacterial 50S ribosomal subunit and thereby blocking translation, whereas the synergic combination of both substances is up to hundred fold more effective than the single compounds, resulting in a bactericidal activity. The streptogramin biosynthetic genes are organized as large antibiotic superclusters. These clusters harbour numerous regulatory genes, which encode different types of regulators that together form a complex hierarchical signalling system, which governs the regulation of streptogramin biosynthesis. Resistance is also regulated by this cascade. However, whereas resistance against streptogramins is quite well understood in diverse pathogenic organisms, only little is known about how the natural producer strains protect themselves against these toxic compounds. Here, we give an overview about the recent advances in streptogramin investigations with a main focus on the best-studied representatives, pristinamycin and virginiamycin. We concentrate on the biosynthesis of these compounds, their regulation and resistance determinants as well as their application in medicine and food industry.

[An uncommon cutaneous presentation of cat scratch disease]. / Présentation cutanée atypique d'une maladie des griffes du chat.

BACKGROUND: Herein we report a case of cat scratch disease on account of its atypical presentation. PATIENTS AND METHODS: A 21-year-old woman presented erythema nodosum associated with painful bilateral inguinal adenopathy, odynophagia, joint pain and evening urticaria in a setting of impaired general condition. Initial serological testing for Bartonella henselae was negative. PCR for Bartonella henselae performed on an adenectomy fragment was positive. A favourable outcome was achieved with azithromycin. COMMENTS: This case shows an atypical and severe presentation of cat scratch disease and raises the problem of sensitivity of serotyping.

Emergence of Staphylococcus aureus strains resistant to pristinamycin in Sfax (Tunisia).

AIM: We report the emergence of Staphylococcus aureus resistant to pristinamycin in Tunisia, and the characterization of the mechanisms of resistance to macrolides and streptogramins. METHODS AND RESULTS: Five strains of S. aureus resistant to pristinamycin were recovered from the department of dermatology in a Tunisian university hospital from skin samples after oral use of pristinamycin between 2004 and 2007. Susceptibility testing showed that all isolates were resistant to quinupristin-dalfopristin (MIC=4-32mg/L), lincomycin, gentamicin, kanamycin, tobramycin, tetracycline and rifampin. One isolate was susceptible to erythromycin. All five strains were closely related after analysis by pulsed-field gel electrophoresis. erm(C) was amplified from three strains and erm(A) from one strain. vga and vat genes were amplified from all strains. None of the isolates carried the vgb gene. The vga and vat genes were typed as vga(B) and vat(B) by restriction profiles analysis after electrophoresis. CONCLUSION: This is the first report of clonal emergence of S. aureus resistant to pristinamycin carrying vga and vat genes in Tunisia. The role of selective pressure of pristinamycin use is certainly the main explanation of this emergence. So we must reduce the utilisation of this antibiotic for the treatment of cutaneous and bone infectious disease caused by multidrug resistant bacteria.

[Antibiotic resistance as a public health problem: the case of genital mycoplasmoses]. / L'antibiotico resistenza un problema di sanità pubblica: il caso delle micoplasmosi genitali.

Antibiotic resistance is an emerging public health problem especially due to the continuous use of antibiotics that selects more aggressive and resistant species. In the present study the authors determined the antibiotic sensitivity of 128 Mycoplasma hominis strains obtained from urethral swabs of male patients (mean age 36 years). The Mycoplasma IST 2 strip was used to test antibiotic susceptibility: 88% of analysed strains were found to be resistant to erythromycin and azithromycin, 75% to clarithromycin, 50% to ofloxacin and ciprofloxacin, and 12% to tetracycline. All strains were susceptible to josamycin, doxycycline and pristinamycin. Results were comparable to those of a recent study by Savarino-Mattei which also showed high resistance of M hominis to macrolide antibiotics and to ciprofloxacin and susceptibility to tetracyclines. Doxycycline is currently the antibiotic of first choice for treating M hominis infections.

Mycobacterium abscessus skin infection after tattooing: first case report and review of the literature.

Mycobacterium abscessus is a species of rapidly growing mycobacteria (RGM). This species can cause skin and soft tissue infections after trauma or surgical procedures, pulmonary infections and disseminated diseases in immunocompromised patients. It has been rarely documented after tattoo procedures. Herein we describe the case of a 51-year- old man who presented with erythematous papules over a tattoo on the back 10 days after a tattoo session. Culture revealed M. abscessus. Tattoo infections, clinical features and treatment options due to RGM are reviewed.

Use of pristinamycin for infections by gram-positive bacteria: clinical experience at an Australian hospital.

Thirty-six patients were treated with pristinamycin for 46 different microbiological isolates between April 2007 and July 2009. Pathogens included 9 methicillin-resistant Staphylococcus aureus isolates, 13 methicillin-resistant coagulase negative staphylococci, and 9 vancomycin-resistant enterococci. Sites of infections included 12 osteomyelitis cases, 10 prosthetic joints, 4 other prostheses, and 1 epidural abscess. Five patients ceased treatment due to side effects. Ten patients were cured of their infections, and 21 patients had infections successfully suppressed.

[Cutaneous ulcers and glycogen storage disease type 1b]. / Ulcères cutanés au cours d'une glycogénose de type 1b.

BACKGROUND: Glycogen storage disease type 1b is a rare disorder caused by 6-glucose-phosphatase transport deficiency. It is characterised primarily by metabolic disorders combined with hypoglycaemia and hyperlactacidaemia and a predisposition to staphylococcal infections associated with polynuclear neutrophil abnormality. Herein, we report the case of a patient with glycogen storage disease type 1b who developed ulcers of the lower limbs and we discuss the possible significance of this association which, to our knowledge, has not yet been described in the medical literature. PATIENTS AND METHODS: A 38-year-old man, presenting glycogen storage disease type 1b diagnosed when he was 13 months old, was hospitalised for ulcers of the lower limbs occurring over the preceding five years. The patient had a quantitative polynuclear neutrophil deficit that was treated with filgrastim. The various ulcers all developed according to the same pattern, namely pustules progressing towards necrosis followed by painful ulceration. No fever or collection of pus was observed. A number of samples of pustules proved sterile while others contained Staphylococcus aureus, sensitive to numerous antibiotics. Histopathological examination proved relatively inconclusive and laboratory tests showed no vascular cause of the ulcers. DISCUSSION: Hypothetical diagnoses of staphylococcal ecthyma suggested by the neutrophil deficiency and of pyoderma gangrenosum were proposed but could not be confirmed with certainty. Involvement of other predisposing factors independent of the patient's glycogen storage disease cannot be ruled out. This combination, not previously reported, nevertheless deserves to be singled out, despite its as yet unclear significance.

Factors associated with emergence of pristinamycin-resistant Staphylococcus aureus in a dermatology department: a case-control study.

BACKGROUND: Pristinamycin is used for the treatment of Staphylococcus aureus skin infection. Staphylococcus aureus pristinamycin resistance is usually low. The frequency of pristinamycin-resistant S. aureus (PRSA) increased in the Caen University Hospital dermatology department from 1% in 1998 to >11% in 1999-2002. OBJECTIVES: This study aimed to identify the factors associated with PRSA acquisition. METHODS: Incidences of PRSA and pristinamycin consumption were calculated for the dermatology department and for the rest of the hospital from 1997 to 2007. Individual factors of PRSA acquisition in the dermatology department from 2000 to 2001 were analysed in a retrospective case-control study including 23 cases of PRSA skin colonization or infection and 46 controls with pristinamycin-susceptible S. aureus. Clonal relatedness of isolates was analysed by pulsed-field gel electrophoresis and pristinamycin resistance genes were detected by polymerase chain reaction. Conditional logistic regression was performed to analyse the relationship between pristinamycin resistance and epidemiological and microbiological data. RESULTS: PRSA frequency and pristinamycin consumption were significantly higher in the dermatology department than in other hospital departments. Two epidemic clones of two and six isolates were found for periods of 1 and 2 months, respectively. Thirteen of the 23 PRSA isolates (57%), including all isolates of the two epidemic clones, were found 48 h after the hospitalization or later. PRSA was associated with pristinamycin use during the previous year [odds ratio (OR) 5.60, 95% confidence interval (CI) 1.41-22.22], cumulative use of antibiotics exceeding 1 week during the previous year (OR 4.63, 95% CI 1.47-14.54) and methicillin resistance (OR 6.35, 95% CI 1.38-29.15). CONCLUSIONS: Results suggest that antimicrobial selective pressure and microbial cross-transmission are involved in PRSA acquisition.

Superficial community-acquired skin infections: prevalence of bacteria and antibiotic susceptibility in France.

OBJECTIVE: Evaluation of the susceptibility to currently used antibiotics of bacteria, particularly S. aureus isolated from superficial community- acquired skin infection and to compare results with those from an earlier study. METHODS: Every dermatologist in community practice participating in the study was asked to include the first two patients consulting them for superficial cutaneous bacterial infection. Swab specimens collected from the skin infection were sent to a central laboratory. RESULTS: The dermatologist enrolled 390 patients in the study. The rate of positive culture was 49%, 259 bacterial strains were isolated. S. aureus was the major species (56.8% of all isolated strains). S. aureus was resistant to methicillin in 4%. All strains of S. aureus were susceptible to pristinamycin and mupirocin. CONCLUSIONS: The results of the two epidemiological studies of superficial community acquired skin infections with a comparable methodology at a 6-year interval demonstrated that the prevalence of CA-MRSA skin infection remained low in this setting.

[Staphylococcic necrotizing pneumopathy due to Panton-Valentine leukocidin toxin with good outcome]. / Pneumopathie nécrosante staphylococcique productrice de leucocidine de Panton-Valentine d'évolution favorable.

Panton-Valentine leukocidin (PLV) is a toxin produced by Staphylococcus aureus. Previously described as responsible for furunculoses and cutaneous abscesses, it was recently found to cause necrotizing pneumonia, generally lethal. We describe a case of necrotizing pneumonia caused by S. aureus containing PLV with an atypical form (bubble form), which had a good outcome despite several risk factors for death: hemoptysis, leukopenia, erythrodermia.