Macrolides for the treatment of chronic bacterial prostatitis: an effective application of their unique pharmacokinetic and pharmacodynamic profile (Review).

Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate characterized by poor quality of life mainly due to frequent relapse episodes caused by incomplete eradication of causative pathogens. Aggressive antibacterial therapy is required to attenuate the severe symptoms of CBP and to achieve a permanent cure. Although fluoroquinolones are currently recommended as first-choice agents, macrolide antibiotics are emerging as a noteworthy option for the treatment of CBP. Macrolide antibiotics are characterized by an impressive array of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These properties include high intracellular accumulation in phagocytes and at sites of infection, including the prostate; broad antibiotic but also biofilm-inhibiting properties; immunomodulating and inflammation-resolving activities. These features offer particular advantages for the treatment of chronic infections of the prostate gland, which are not easily amenable to drug therapy. Macrolides may be exploited to counteract the unsatisfactory rates of clinical symptom improvement and pathogen eradication. The results of a number of clinical trials support this proposal.

A switch therapy protocol with intravenous azithromycin and ciprofloxacin combination for severe, relapsing chronic bacterial prostatitis: a prospective non-comparative pilot study.

Chronic bacterial prostatitis (CBP) is characterized by intense clinical symptoms, frequent relapse episodes and poor quality of life. Aggressive antibacterial therapy is warranted to eradicate the causative pathogens and to achieve a permanent cure. We administered a "switch-therapy" protocol to 30 patients showing severe CBP symptoms and two or more relapse episodes in the previous 12 months. Patients received intravenous azithromycin (500 mg/day) and ciprofloxacin (800 mg/day) for 3 days, followed by oral ciprofloxacin (1 g/day) for 25 days.Twenty-seven (90%) patients showed pathogen eradication at test-of-cure (TOC) visit. Five cases of infection relapse were detected at follow-up. At the TOC visit, 25 patients (83%) showed mild/absent symptoms, measured with the NIH-chronic prostatitis symptom index.These results indicate the efficacy of a "switch-therapy" protocol, based on combined azithromycin and ciprofloxacin. Comparative studies on larger CBP patient populations are warranted to confirm these encouraging results.

Eradication of Chlamydia trachomatis parallels symptom regression in chronic bacterial prostatitis patients treated with a fluoroquinolone-macrolide combination.

To investigate the association between eradication of Chlamydia trachomatis (CT) and symptom regression in chronic prostatitis, 55 symptomatic patients were subjected to segmented tests to localise CT in first voided urine (VB1), prostatic secretions (EPS), post-massage voided (VB3) or semen specimens. Patients were divided in three treatment groups: the 'urethral involvement' group ('U': VB1 positive, EPS/VB3/Semen negative) was treated with 500 mg day(-1) azithromycin for 3 days. The 'prostatitis' group ('P': VB1 negative, EPS/VB3/semen positive) with 4-week levofloxacin-azithromycin combination. A third group, 'U+P' (VB1, EPS/VB3/semen positive) received both treatments in sequence. In P patients, eradication of CT was paralleled by marked, sustained symptom improvement and by significant decrease of serum prostate-specific antigen (PSA) levels. Compared with U patients, undergoing rapid regression of symptoms related to painful micturition after short-term azithromycin, U+P patients showed symptom and pathogen persistence in VB3/EPS/semen and required additional treatment with 4-week levofloxacin-azithromycin to achieve pathogen eradication, symptom regression, and decrease of PSA. Our results support a causative role of CT in chronic bacterial prostatitis. In the presence of a positive urethral localisation of the pathogen, thorough microbiological investigation together with focused symptom analysis may reveal an underlying chlamydial prostatitis and direct effective therapy with appropriate antibacterial agents.

Is the clinical picture of Schnitzler syndrome always Schnitzler syndrome?

Here we present two cases, a female and a male patient with Schnitzler-like syndrome. Both patients had two major (monoclonal gammopathy and chronic urticaria) and almost all minor symptoms (e.g. arthralgia, bone pain, fever, etc.) of Schnitzler syndrome. It is considered that interleukine (IL)-1 has important influence on immunopathogenesis of Schnitzler syndrome. However, when looked at the immune response in our two patients, we found significant differences between them. In the sera of the female patient, IL-1beta was increased. However, the highest increase was found for granulocyte- colony stimulating factor (G-CSF), IL-32 alpha and IL-17E (IL-25). The male patient had a significant increase in the percentage of NK-cells, a decrease in CD4+ helper cells and no increase in cytokine levels. In both patients an increase in CD40L (CD154) was found. Our statement is that, besides clinical symptoms and signs, additional immune parameters should be tested before diagnosis of Schnitzler syndrome is established.

Comparative analysis of azithromycin and clarithromycin efficacy and tolerability in the treatment of chronic prostatitis caused by Chlamydia trachomatis.

A total of 123 patients, older than 18 years of age, with symptoms of chronic prostatitis and inflammatory findings as well as the presence of Chlamydia trachomatis confirmed by DNA/RNA DIGENE hybridization method in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage, were examined. The patients were randomized to receive a total of 4.5 g of azithromycin for 3 weeks, given as a 3-day therapy of 1 x 500 mg weekly or clarithromycin 500 mg b.i.d. for 15 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy were evaluated 4-6 weeks after the end of therapy. In the group of patients with chronic chlamydial prostatitis the eradication rates (azithromycin 37/46, clarithromycin 36/45) and the clinical cure rates (azithromycin 32/46, clarithromycin 32/45) were not significantly different with regards to the administered drug (p > 0.05). In the group of patients with asymptomatic chlamydial prostatitis the eradication rates (azithromycin 11/16, clarithromycin 10/15) were not significantly different with regards to the administered drug (p = 1.00, OR = 1.1).

Gentamicin concentrations in urine, cortex and medulla in an acutely obstructed kidney animal model.

Gentamicin was administered intraperitoneally, three times in 12 h to Hartley type guinea-pigs which had undergone complete unilateral ureteral obstruction with normal contralateral ureteral function for either 24 hours, 7 days or 21 days. Two hours after the last drug dose urine samples were collected from urinary bladder and obstructed ureter. Healthy and obstructed kidneys were then surgically removed from all sacrificed animals. Gentamicin concentration in urine of healthy kidney was 112-266 microg/ml, and in obstructed kidney 18-53 microg/ml, with a tendency of linear decrease over a 3-week obstruction period. The gentamicin concentration in obstructed renal cortex never exceeded one-third of the gentamicin concentration in unobstructed renal cortex. The maximum gentamicin concentration in obstructed renal medulla was 75% of the gentamicin concentration in unobstructed renal medulla.

Duration of clinical symptoms in female patients with acute urethral syndrome caused by Chlamydia trachomatis treated with azithromycin or doxycycline.

One hundred fifty-one female patients with acute urethral syndrome caused by Chlamydia trachomatis were examined. First, patients were divided into two groups, those with clinical symptoms present < 3 weeks before the start of treatment, and those with clinical symptoms > or = 3 weeks prior to the beginning of therapy. Then patients were further divided into groups and randomized to receive azithromycin once daily in a single dose of 1.0 g or 500 mg once daily for 6 days, or to receive doxycycline 100 mg b.i.d. for 14 days or 100 mg b.i.d. for 7 days (8 study groups in all). Clinical and bacteriological efficacy was evaluated 3 weeks after the end of therapy. In the group of patients with disease symptoms lasting for 3 weeks or longer, the eradication and clinical cure rates were significantly higher after administration of azithromycin in a dose of 1x500 mg/6 days than after a single dose of 1.0 g (p<0.01), and after administration of doxycycline 2x100 mg/14 days than by using doxycycline 2x100 mg/7 days (p<0.05).

[Antimicrobial therapy of urinary tract infections]. / Antimikrobno lijecenje infekcija mokracnog sustava.

Urinary tract infections (UTIs), according to localization of infection, can be subdivided into urethritis, cystitis, prostatitis and pyelonephritis, according to type of infection into symptomatic, asymptomatic, acute (first or single), recurrent, chronic, complicated and uncomplicated. Clinical symptoms of cystitis and leukocyturia are sufficient reason for early initiation of a three-day empirical antimicrobial therapy of acute uncomplicated cystitis in young women. Urine culture should be performed prior to the initiation of antimicrobial therapy in pregnant women, diabetics, recurrent UTIs, in case of unsuccessful prior treatment and in patients with pyelonephritis. All symptomatic UTIs should be treated, as well as asymptomatic bacteriuria in pregnant women, diabetics, preschool children and prior to urologic-gynecologic surgery. In complicated UTIs it is especially important to determine and try to eliminate or at least put under control the factors that complicate UTIs. Antimicrobial therapy of UTIs includes fluoroquinolones, co-trimoxazole, betalactam antibiotics, aminoglycosides and nitrofurantoin, tetracyclines, macrolides, and azalydes in case of sexually transmitted diseases caused by Chlamydia trachomatis and Ureaplasma urealyticum. Cystitis is treated for 1, 3 or 7 days, asymptomatic bacteriuria 3-7 days, uncomplicated pyelonephritis 10-14 days, bacterial prostatitis 4-8 weeks, and chronic nonbacterial prostatitis 2-4 weeks. Recommended therapy for chronic and complicated UTIs is 7-14 days only in relapses and reinfections, and in some patients it can last for several weeks, up to 6 months. Chemoprophylaxis in recurrent uncomplicated UTIs should be employed for at least 6 months.

Azithromycin and doxycycline in the treatment of female patients with acute urethral syndrome caused by Ureaplasma urealyticum: significance of duration of clinical symptoms.

One hundred ninety-two female patients with acute urethral syndrome caused by Ureaplasma urealyticum were examined. First, patients were divided into two groups: those with clinical symptoms present for less than 3 weeks before the start of treatment and those with clinical symptoms 3 weeks or longer before the beginning of therapy. The patients were then further divided into groups and randomized to receive azithromycin once daily in a single dose of 1 g or 500 mg once daily for 6 days, or to receive doxycycline 100 mg b.i.d. for 14 days or 100 mg b.i.d. for 7 days (eight study groups in all). Clinical and bacteriological efficacy were evaluated 3 weeks after the end of therapy. In the group of patients with disease symptoms lasting for 3 weeks or longer, eradication and clinical cure rates were significantly higher after the administration of azithromycin at a dose of 1 x 500 mg/6 days than after a single dose of 1 g (p < 0.001).

Urinary tract infections in HIV disease.

HIV-positive patients are liable to acquire opportunistic infections. Their liability to acquire other common infectious conditions is less frequently reported. In order to determine the frequency of urinary tract infections (UTI) in HIV-positive patients, we performed a retrospective analysis. The control group was formed from patients with community acquired pneumonia. We reviewed charts of 96 HIV-positive patients and of 314 patients in the control study group. The analysis has shown that patients with HIV had a UTI more frequently than the controls. Besides the difference in the frequency, we observed the difference in the etiology. Enterococci were the most frequent isolates in patients with HIV disease, whereas Escherichia coli was most frequently isolated in the controls. These facts should be taken into consideration when treatment of a UTI with suspected bacteremia in AIDS patients is initiated.

Azithromycin: single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome--a randomized study.

An open comparative study was undertaken in order to assess the efficacy and safety of a single dose of azithromycin in the treatment of community-acquired atypical pneumonia. A total of 100 adult patients with atypical pneumonia syndrome were randomized to receive 1.5 g of azithromycin as a single dose, or 500 mg once daily for 3 days. The presence of Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, and Legionella pneumophila infection was diagnosed by serological tests. Control clinical examinations were performed 72 h, 10-12 days and 4 weeks after treatment initiation. Among 96 patients (48 in each group) who were evaluable for clinical efficacy M. pneumoniae infection was confirmed in 24, C. pneumoniae in nine, C. psittaci in five, C. burnetii in six, and L. pneumophila in five. Forty-seven patients (97.9%) in each group were cured. Side effects were observed in two patients in the single-dose group, and one patient in the 3-day group. In conclusion, a single 1.5 g dose of azithromycin may be an alternative to the standard 3-day azithromycin regimen in the treatment of outpatients with atypical pneumonia syndrome.

[Cholinesterase in plasma and cerebrospinal fluid in patients with viral meningitis]. / Kolinesteraza u plazmi i cerebrospinalnom likvoru bolesnika s virusnim meningitisom.

Pseudocholinesterase activity (PChE) in human plasma and cerebrospinal fluid was determined in 30 patients; in 15 patients with acute viral meningitis and in 15 patients with meningism. Concentration of total proteins in cerebrospinal fluid was also determined. PChE activity and protein concentration in cerebrospinal fluid of patients with meningitis is significantly higher than in control group (P < 0.001). Relationship of PChE activity and protein concentrations in cerebrospinal fluid of patients with meningitis does not differ from that in the control group patients. Thus, the increase of PChE activity in the cerebrospinal fluid of patients with viral meningitis suggests an alteration in the blood-brain barrier, leading to an increase in the passage of serum components.