Combination Therapy with Betamethasone and Josamycin Demonstrates Superior Therapeutic Efficacy in an NC/Nga Mouse Model of Atopic Dermatitis.

We have previously demonstrated the excellent bactericidal activity of josamycin against Staphylococcus aureus isolated from patients with atopic dermatitis (AD), with therapeutic efficacy equal to that of betamethasone. The present study was designed to evaluate the effectiveness of combination therapy with betamethasone and josamycin for AD. Betametasone (0.1%) and josamycin (0.1%) were topically administered to NC/Nga mice with severe AD-like skin lesions. Skin severity scores, histological changes in skin lesions, and serum immunoglobulin E (IgE) levels were assessed as indicators of therapeutic efficacy. Topical treatment with both drugs suppressed the skin severity score to a greater degree than betamethasone alone. This was associated with a reduction of epidermal thickening, a reduced density of dermal cellular infiltration, a decreased mast cell count in the dermis, and a reduced serum IgE level. In addition, both drugs in combination markedly reduced the expression of interferon (IFN)-γ and interleukin (IL)-4 in auricular lymph node cells, as well as the S. aureus count on the lesioned skin. These results show that simultaneous topical application of both drugs can ameliorate severe AD-like skin lesions in NC/Nga mice. It is suggested that combination therapy with betamethasone and josamycin would be beneficial for control of severe AD lesions colonized by S. aureus by inhibiting the development of both T helper (Th) type 1 (Th1) and Th2 cells and also through elimination of superficially located S. aureus.

Effects of Josamycin on Scratching Behavior in NC/Nga Mice with Atopic Dermatitis-Like Skin Lesions.

Our previous study showed that chronic skin colonization by Staphylococcus aureus exacerbated atopic dermatitis (AD) and that control of such skin colonization using antibiotic ointment might relieve AD-related skin inflammation. However, the role of S. aureus colonization in the pruritus accompanying AD was not elucidated. The aim of the present study was to evaluate the effect of topically applied josamycin, a macrolide antibiotic, on the scratching behavior of NC/Nga mice with AD-like skin lesions. Josamycin (0.1%) was topically administered to NC/Nga mice with AD-like skin lesions induced by a mite antigen, Dermatophagoides farinae extract, and the therapeutic effects of josamycin were assessed by measurement of the skin severity score, S. aureus colonization, scratching count, and interleukin (IL)-31 mRNA expression in the skin lesions. Topical treatment with josamycin ointment significantly suppressed the increase of the skin severity score in NC/Nga mice. This suppressive effect was associated with decreases in the S. aureus count on the lesioned skin, scratching behavior of mice and IL-31 mRNA expression in the lesions. The present results show that the severity of AD-like skin inflammation in NC/Nga mice is correlated with the level of S. aureus colonization and subsequent IL-31 production in the skin. Therefore, topical application of josamycin to AD lesions colonized by S. aureus would be beneficial for control of AD by eliminating superficially located S. aureus and by suppressing the IL-31-induced scratching behavior.

Randomized Trial of Clarithromycin for Mediterranean Spotted Fever.

The classic antibiotic treatment for Mediterranean spotted fever (MSF) is based on tetracyclines or chloramphenicol, but chloramphenicol's bone marrow toxicity makes tetracyclines the treatment of choice. However, it is convenient to have alternatives available for patients who are allergic to tetracyclines, pregnant women, and children <8 years old. We conducted a randomized clinical trial to compare clarithromycin with doxycycline or josamycin in the treatment of MSF. Forty patients were evaluated (23 male; mean age, 39.87 years); 13 patients were aged <14 years. Seventeen patients received clarithromycin, and 23 received doxycycline or josamycin. The interval between the onset of symptoms and the start of treatment was 4.04 ± 1.70 days in the clarithromycin group versus 4.11 ± 1.60 days in the doxycycline/josamycin group (P = not significant [NS]). Time to the disappearance of fever after treatment was 2.67 ± 1.55 days in the clarithromycin group versus 2.22 ± 1.35 days in the doxycycline/josamycin (P = NS). The symptoms had disappeared at 4.70 ± 2.25 days in the clarithromycin group versus at 4.75 ± 3.08 days in the doxycycline/josamycin (P = NS). There were no adverse reactions to treatment or relapses in either group. In conclusion, clarithromycin is a good alternative to doxycycline or josamycin in the treatment of MSF.

[DOXYCYCLINE (UNIDOX SOLUTAB®) AND/OR JOSAMYCIN (WILPRAFEN®) IN TREATMENT OF PATIENTS WITH PROSTATITIS IN REAL CLINICAL PRACTICE. RESULTS OF THE TAURUS OBSERVATIONAL PROGRAM].

Treatment of chronic prostatitis is a vital and complicated problem, in which a large number of stamps and "stereotyped" approaches often result in uncured patients. The increasing use of intracellular microorganisms in prostatitis etiology requires a modification in the standard approaches. TAURUS study shows high efficacy of doxycycline (Unidox Solutab®) and/or josamycin (Wilprafen®) in chronic prostatitis. Therapy, studied in this program, according to physicians, was effective in 93.2% of patients. Treatment failure was observed in 1.3% of all patients, another 5.5% of patients had insufficient data for assessment. Low incidence of adverse reactions was observed. In the study population, adverse reactions occurred in 2.6% of patients, of them serious adverse events were registered in 0.7% of patients. The most common adverse event in all treatment groups was diarrhea.

Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin.

BACKGROUND: Azithromycin has been widely used for Mycoplasma genitalium treatment internationally. However, the eradication efficacy has substantially declined recent decade. In Russia, josamycin (another macrolide) is the recommended first-line treatment for M. genitalium infections, however, no data regarding treatment efficacy with josamycin and resistance in M. genitalium infections have been internationally published. We examined the M. genitalium prevalence in males attending an STI clinic in Moscow, Russia from December 2006 to January 2008, investigated treatment efficacy with josamycin in male urethritis, and monitored the M. genitalium DNA eradication dynamics and selection of macrolide resistance in M. genitalium during this treatment. METHODS: Microscopy and real-time PCRs were used to diagnose urethritis and non-viral STIs, respectively, in males (n = 320). M. genitalium positive patients were treated with recommended josamycin regimen and treatment efficacy was monitored using quantitative real-time PCR. Macrolide resistance mutations were identified using sequencing of the 23S rRNA gene. RESULTS: Forty-seven (14.7%) males were positive for M. genitalium only and most (85.1%) of these had symptoms and signs of urethritis. Forty-six (97.9%) males agreed to participate in the treatment efficacy monitoring. All the pre-treatment M. genitalium specimens had wild-type 23S rRNA. The elimination of M. genitalium DNA was substantially faster in patients with lower pre-treatment M. genitalium load, and the total eradication rate was 43/46 (93.5%). Of the six patients with high pre-treatment M. genitalium load, three (50%) remained positive post-treatment and these positive specimens contained macrolide resistance mutations in the 23S rRNA gene, i.e., A2059G (n = 2) and A2062G (n = 1). CONCLUSIONS: M. genitalium was a frequent cause of male urethritis in Moscow, Russia. The pre-treatment M. genitalium load might be an effective predictor of eradication efficacy with macrolides (and possibly additional antimicrobials) and selection of macrolide resistance. Additional in vivo and in vitro data are crucial to support the recommendation of using josamycin as first-line treatment for M. genitalium infections in Russia. It would be valuable to develop international M. genitalium management guidelines, and quantitative diagnostic PCRs determining also M. genitalium load and resistance mutations (for macrolides and ideally also moxifloxacin) should ideally be recommended.

[Update on SENLAT syndrome: scalp eschar and neck lymph adenopathy after a tick bite]. / Les nouveautés sur le syndrome SENLAT : Scalp Eschar and Neck LymphAdenopathy after Tick bite.

SENLAT syndrome, also known as TIBOLA/DEBONEL, is an emerging disease in France. The major symptoms are necrotic eschar on the scalp associated with painful cervical lymphadenopathy. It occurs mainly in women and children during the cold seasons after a bite by a Dermacentor tick, responsible for transmitting Rickettsia slovaca or Rickettsia raoultii. Cutaneous swabs are safe, easy and reliable tools that should be used routinely by physicians to confirm diagnosis. In this particular disease, they should be preferred to serology, which is less sensitive. Doxycycline is the antibiotic of choice for this syndrome.

[Unusual presentation of a severe Mycoplasma pneumoniae infection: report of 2 cases]. / Présentation inhabituelle d'une infection grave à Mycoplasma pneumoniae, à propos de 2 observations.

Mycoplasma pneumonia is responsible for multisystemic infection. Pulmonary symptoms are most common in children. We describe herein two unusual severe forms of M. pneumoniae infection without initial pulmonary symptoms. The first case is an 8-month-old boy who was hospitalized in the pediatric intensive care unit with severe sepsis. There were no initial pulmonary symptoms, nor obvious clinical infection. Initial blood tests and x-ray did not aid the diagnosis. The blood tests came back positive for M. pneumonia. Pulmonary symptoms eventually appeared 24h later, and there was a pneumonia outbreak on the chest radiograph. The boy was given josamycin and improved quickly. The second case concerns an 8-year-old child who was hospitalized in the pediatric intensive care unit with toxic shock. No clinical infectious origin was found. A broad-spectrum antibiotic therapy was started with ceftriaxone and josamycin. The M. pneumoniae blood test came back positive, which confirmed the diagnosis of septic shock in M. pneumoniae, requiring adjustment of the antibiotic therapy. Current guidelines for the choice of probabilistic antibiotic therapy in case of severe sepsis do not include the case of M. pneumoniae. The early initiation of antibiotic therapy plays a major role in the prognosis of these patients. It seems useful to search for M. pneumoniae in cases of severe atypical infections, particularly in the absence of pulmonary symptoms.

Acute encephalitis associated to a respiratory infection due to Chlamydophila pneumoniae.

OBJECTIVE: Chlamydophila pneumoniae is a common agent of respiratory infections. Severe acute neurological infections are very infrequently linked to this bacterium. We report such a case and give a rapid overview of published cases of acute encephalitis occurring after a respiratory infection due to C. pneumoniae. PATIENT AND METHODS: A 12-year-old child without any prior medical history was hospitalized for encephalitis associated to respiratory symptoms. RESULTS: C. pneumoniae DNA was identified by multiplex PCR assay in respiratory secretions and C. pneumoniae IgM and IgG antibodies were assessed in the serum. This bacterium was not detected in CSF, nor was any other pathogen. A macrolide treatment was prescribed for two weeks. The outcome was good without any sequels. CONCLUSIONS: This observation correlates to the few similar cases reported in the medical literature. C. pneumoniae must be suggested in the etiological diagnosis of acute encephalitis, notably in a context of respiratory infection, when no more common cause can be identified.

[Diagnostic and treatment patterns in management of male patients with nongonococcal urethritis: results of Russian multicentral cross-sectional study].

The aim of the study was to estimate the diagnostic and treatment patterns in the management of acute nongonococcal urethritis (NGU) in males in some cities of Russia. Retrospective cross-sectional study was conducted in 2009 in 5 centers of 4 cities in the Central Part of Russia (Kaluga, Pskov, Smolensk - 2 centres and Tula). The data on the diagnostic and treatment approaches to the management of NGU in male subjects >16 years old were collected and analyzed with the use of specially designed case report forms. 556 cases of acute urethritis were analyzed during the study. The diagnosis of NGU was confirmed in 401 cases. The average age of the patients was 29.8 years (16-68 years). The following diagnostic methods were used in 95% of the cases: urethral smear microscopy (314/82.4%), C. trachomatis - PCR (113/29.7%), ELISA (155/40.7%); T. vaginalis - PCR (106/27.8%); U. urealyricum and M. hominis, respectively - bacteriology (140/36.7% and 126/33.1%), PCR (110/28.9% and 108/28.3%); M. genitalium - PCR (110/28.9%). The treatment patterns included antimicrobials AMs alone in 60.3, and AMs + non-AMs in 37.8% of the cases. The most frequently prescribed AMs were azithromycin (27.5%), fluconazole (16.4%), doxycycline (13.6%), metronidazole (11.2%), ofloxacine (7.3%), ceftriaxone (4.4%), josamycin (4.2). According to the results use of the standard methods for NGU diagnosis was rather rare. The use of PCR for atypical pathogens was the following: C. trachomatis 29.7%, U. urealyticum 36.7%, M. hominis 28.9%, M. genitalium 28.3%. Doubtful culture methods were used for detection of U. urealyticum and M. hominis (36.7% and 33.1%). The AMs treatment in some cases was not in compliance with the up-to-date practical guidelines for STD and NGU.

[The influence of ultrasonic radiation on the factors of antimicrobial resistance in the women of reproductive age presenting with mycoplasma infection of the urogenital tract].

The present clinical immunological study included 90 women of reproductive age presenting with mycoplasma infection of the lower urogenital tract. Low-frequency ultrasonic radiation was shown to successfully correct the disbalance in the system of congenital immunity that manifested itself as marked dysfunction of neutrophil granulocytes. The local application of low-frequency ultrasonic radiation normalized concentration of neutrophil defensins in cervical secretion as well as the number and function of neutrophils themselves.

[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.

[Streptococcal perianal dermatitis and guttate psoriasis]. / Anite streptococcique et psoriasis en gouttes.

BACKGROUND: The link between guttate psoriasis and streptococcal infection is acknowledged. This form of psoriasis generally follows pharyngitis, but a small number of cases have been described as being triggered by a streptococcal infection other than in the throat. We report the case of a child with streptococcal anitis followed by guttate psoriasis. CASE REPORT: A 4-year-old boy presented painful perianal erythema present for two weeks with diffuse lesions of guttate psoriasis present since the second week. Group A beta-haemolytic streptococcus was found during bacterial examination of the anal region. After one month of antibiotic treatment with josamycin combined with daily application of desonide 0.05% topical cream, all symptoms subsided without relapse in the ensuing 6 months. DISCUSSION: This case demonstrates the need for careful clinical examination, both of the nose and throat but also of the perianal region, in children consulting for guttate psoriasis. It also demonstrates the strong link between guttate psoriasis and streptococcal infections in certain patients.

[Is it safe to use josamycin in the obstetrics practice in Russia?].

The present situation with the use of antimicrobial drugs for the management of Chlamydia trachomatis infection during pregnancy in the Russian Federation was evaluated. The efficacy and safety of various macrolides in the treatment of chlamydial infection in practical obstetrics were analyzed. It was conclude that josamycin was inferior to azithromycin by a number of pharmacologic parameters, compliance and safety and therefore should not be used in pregnant women.

[Evaluation of efficacy and safety of josamycin (Vilprafen) in the treatment of patients with community-acquired pneumonia].

Clinical and bacteriological efficacy ofjosamycin (Vilprafen), a macrolide antibiotic, was studied in 30 out- and inpatients at the age of 18 to 68 years (the average of 43.4+/-16.7 years old) with nonsevere (PORT) community-acquired pneumonia in the case histories. Josamycin was administered orally in a dose of 500 mg every 8 hours for 7 to 10 days. The treatment course was 5 to 10 days (the average of 7.7+/-1.3 days). The recovery was stated in 28 (93.3%) patients and the pathogen eradication was recorded in 16 (88.9%) patients. Moderate side effects not requiring discontinuation of the drug use were observed in 3 patients. The results of the treatment were indicative of the josamycin high efficacy in the treatment of the patients with nonsevere community-acquired pneumonia.

Treatment failure of nosocomial pertussis infection in a very-low-birth-weight neonate.

We describe a case of nosocomial maternal transmission of Bordetella pertussis to a very-low-birth-weight (VLBW) neonate in whom treatment was unsuccessful. This case underscores the need for rapid and sensitive PCR diagnosis in VLBW neonates and in parents with clinical signs of pertussis and suggests that standard treatment may not be appropriate for VLBW neonates.