rifampin and Endocarditis

Bartonella spp. are responsible for emerging and re-emerging diseases around the world. The majority of human infections are caused by Bartonella henselae, Bartonella quintana and Bartonella bacilliformis, although other Bartonella spp. have also been associated with clinical manifestations in humans. The severity of Bartonella infection correlates with the patient's immune status. Clinical manifestations can range from benign and self-limited to severe and life-threatening disease. Clinical conditions associated with Bartonella spp. include local lymphadenopathy, bacteraemia, endocarditis, and tissue colonisation resulting in bacillary angiomatosis and peliosis hepatis. Without treatment, Bartonella infection can cause high mortality. To date, no single treatment is effective for all Bartonella-associated diseases. In the absence of systematic reviews, treatment decisions for Bartonella infections are based on case reports that test a limited number of patients. Antibiotics do not significantly affect the cure rate in patients with Bartonella lymphadenopathy. Patients with Bartonella spp. bacteraemia should be treated with gentamicin and doxycycline, but chloramphenicol has been proposed for the treatment of B. bacilliformis bacteraemia. Gentamicin in combination with doxycycline is considered the best treatment regimen for endocarditis, and erythromycin is the first-line antibiotic therapy for the treatment of angioproliferative lesions. Rifampicin or streptomycin can be used to treat verruga peruana. In this review, we present recent data and recommendations related to the treatment of Bartonella infections based on the pathogenicity of Bartonella spp.

Topics: Angiomatosis, Bacillary; Anti-Bacterial Agents; Bacteremia; Bartonella; Bartonella Infections; Chloramphenicol; Doxycycline; Drug Administration Schedule; Endocarditis; Gentamicins; Humans; Lymphatic Diseases; Rifampin; Streptomycin; Treatment Outcome; Virulence

In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs).. Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated.. A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics.. For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Topics: Amoxicillin; Anti-Bacterial Agents; Dicloxacillin; Endocarditis; Endocarditis, Bacterial; Humans; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Rifampin

Topics: Anti-Bacterial Agents; Endocarditis; Endocarditis, Bacterial; Humans; Linezolid; Rifampin; Staphylococcal Infections

International guidelines recommend rifampin-based combinations for staphylococcal prosthetic valve endocarditis (PVE). However, no robust clinical data support this recommendation, and rifampin tolerability is an issue. We aimed to evaluate the impact of rifampin for the treatment of staphylococcal PVE.. An observational retrospective cohort study of all adults with staphylococcal PVE (modified Duke criteria) was conducted in 3 referral centers for endocarditis, during years 2000-2018. Primary outcome measurement was 1-year mortality.. We enrolled 180 patients with PVE due to Staphylococcus aureus (n = 114, 63.3%), or coagulase-negative staphylococci (n = 66, 36.7%), on bioprosthesis (n = 111, 61.7%), mechanical valve (n = 67, 37.2%), or both (n = 2). There were 132 males (73.3%), and mean age was 70.4 ± 12.4 years. Valvular surgery was performed in 51/180 (28.3%) cases. Despite all isolates were susceptible to rifampin, only 101 (56.1%) were treated with rifampin, for a median duration of 33.0 days, whereas 79 (43.9%) received no rifampin. Baseline characteristics were similar in both groups. One-year mortality was, respectively, 37.6% (38/101), and 31.6% (25/79), in patients treated with, or without, rifampin (P = .62). Relapse rates were 5.9% (6/101), and 8.9% (7/79), P = .65. Patients treated with rifampin had longer hospital length-of-stay: 42.3 ± 18.6 vs 31.3 ± 14.0 days (P < .0001). On multivariate analysis, only cerebral emboli (odds ratio [OR] 2.95, 95% confidence interval [CI], 1.30-6.70, P = .009), definite endocarditis (OR 7.15, 95% CI, 1.47-34.77, P = .018), and methicillin-resistant S. aureus (OR 6.04, 95% CI, 1.34-27.26, P = .019), were associated with 1-year mortality.. A large proportion (43.9%) of staphylococcal PVE received no rifampin. One-year survival and relapse rates were similar in patients treated with or without rifampin.

Topics: Adult; Aged; Aged, 80 and over; Endocarditis; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections

Cellulosimicrobium cellulans is a gram-positive filamentous bacterium found primarily in soil and sewage that rarely causes human infection, especially in previously healthy adults, but when it does, it often indicates a poor prognosis.. We report a case of endocarditis and intracranial infection caused by C. cellulans in a 52-year-old woman with normal immune function and no implants in vivo. The patient started with a febrile headache that progressed to impaired consciousness after 20 days, and she finally died after treatment with vancomycin combined with rifampicin. C. cellulans was isolated from her blood cultures for 3 consecutive days after her admission; however, there was only evidence of C. cellulans sequences for two samples in the second-generation sequencing data generated from her peripheral blood, which were ignored by the technicians. No C. cellulans bands were detected in her cerebrospinal fluid by second-generation sequencing.. Second-generation sequencing seems to have limitations for certain specific strains of bacteria.

Topics: Actinobacteria; Actinomycetales Infections; Blood Culture; Diagnosis, Differential; Endocarditis; Fatal Outcome; Female; Humans; Middle Aged; Rifampin; Sequence Analysis, DNA; Vancomycin

Topics: Aged, 80 and over; Diabetes Mellitus, Type 2; Doxycycline; Echocardiography; Electroencephalography; Embolism; Endocarditis; Fever; Fluorodeoxyglucose F18; Heart Valve Prosthesis; Humans; Hypertension; Magnetic Resonance Imaging; Male; Myocardial Infarction; Positron Emission Tomography Computed Tomography; Rifampin; Treatment Outcome

Daptomycin is a bactericidal antibiotic approved for the treatment of skin and soft tissue infections and right-side endocarditis. However, there is a lack of published data outlining its usefulness in vascular graft infections (VGI). The aim of this study was to describe the clinical experience of daptomycin use in the treatment of VGI caused by Gram-positive bacteria.. This was a retrospective cohort study of patients diagnosed with VGI receiving daptomycin at a tertiary care hospital during the period January 2010 to December 2012.. Of a total 1066 consecutive patients who had undergone vascular grafts (VG), 25 were diagnosed with VGI. Fifteen of these patients (11 prosthetic VG, three autologous VG, one both types) received daptomycin (median dose 6.7mg/kg/day, range 4.1-7.1mg/kg/day; median age 69 years, range 45-83 years; 80% male). The infected bypass was removed in 13 cases. The most common reason for selecting daptomycin was kidney failure (53%). The Gram-positive organisms isolated were coagulase-negative Staphylococcus (n=10), Staphylococcus aureus (n=3) (two methicillin-resistant S. aureus), Enterococcus faecium (n=2), and Enterococcus faecalis (n=1). The mean follow-up was 69 months (interquartile range 48-72 months). Ten patients (66.7%) achieved complete healing of the VGI. A recurrence of the infection was observed in 100% of patients in whom the bypass was not removed. Among patients who did not achieve complete healing, one needed a supracondylar amputation and one died as a consequence of infection. Five patients received treatment with rifampicin in addition to daptomycin and they were all cured.. The use of daptomycin and surgery for Gram-positive VGI was effective and well tolerated, and this may be a good alternative for the treatment of VGI in patients with peripheral arterial disease in whom renal insufficiency is common.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Daptomycin; Endocarditis; Enterococcus faecalis; Enterococcus faecium; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Recurrence; Retrospective Studies; Rifampin; Skin Diseases, Infectious; Soft Tissue Infections; Staphylococcus aureus; Treatment Outcome; Vascular Grafting; Wound Healing

The cytochrome P450 is a superfamily of isoenzymes that are responsible for the metabolism of many drugs. Significant changes in pharmacokinetics and drug interactions may be due to induction of hepatic cytochrome P450 enzymes. Rifampicin is a common inducer of CYP3A4. We report a case of a 57-year-old woman who was suspected for endocarditis and therefore treated with rifampicin. Due to previous mechanical aortic valve replacement, she also received phenprocoumon for anticoagulation. Although continuing anticoagulant therapy, antibiotic coadministration led to normal international normalised ratio (INR) level. Fifteen days after the treatment with rifampicin ended, INR returned to therapeutic level.

Topics: Anti-Bacterial Agents; Anticoagulants; Aortic Valve Insufficiency; Cytochrome P-450 Enzyme System; Drug Interactions; Endocarditis; Female; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Middle Aged; Phenprocoumon; Rifampin; Treatment Outcome; Vitamin K

Topics: Adult; Anti-Bacterial Agents; Computed Tomography Angiography; Echocardiography; Endocarditis; Floxacillin; Fluorodeoxyglucose F18; Heart Septal Defects, Ventricular; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Positron-Emission Tomography; Prosthesis-Related Infections; Pulmonary Atresia; Pulmonary Valve; Radiopharmaceuticals; Rifampin

Bacillus cereus is a ubiquitous telluric organism. B. cereus endocarditis is a rare condition seen mostly in prosthetic heart valves and among intravenous drug users. We report a new case of a patient without risk factors and with a good clinical outcome not requiring valve replacement.. In October 2014, a 50-year-old woman was referred to the dermatology department of Lille University Hospital for lower-limb wounds developing 6 months earlier. She presented fever without clinical signs of infection, except for the lower-limbs wounds. Blood cultures revealed the presence of B. cereus. Transesophageal echocardiography was performed and revealed two foci of aortic valve vegetation with a diameter of 5mm. After bacterial sensitivity testing, rifampicin and levofloxacin treatment was given for six weeks, with complete remission. A skin graft was performed and good improvement was seen.. Nineteen cases of B. cereus endocarditis have been described previously, only one of which was without risk factors. We described a case of complete remission after a 6-week course of antibiotics. Our case demonstrates that BC should not be considered as a blood culture contamination, and that treatment may be complex due to antibiotic resistance.

Topics: Anti-Bacterial Agents; Bacillus cereus; Drug Therapy, Combination; Endocarditis; Female; Humans; Leg Ulcer; Levofloxacin; Middle Aged; Rifampin; Risk Factors; Time Factors; Treatment Outcome

Topics: Abscess; Adolescent; Allografts; Aorta; Aortic Rupture; Aortic Valve; Aortic Valve Insufficiency; Bicuspid Aortic Valve Disease; Cardiac Surgical Procedures; Chest Pain; Drug Resistance, Bacterial; Dyspnea; Endocarditis; Gentamicins; Heart Murmurs; Heart Valve Diseases; Humans; Male; Nafcillin; Pericardial Effusion; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis; Vancomycin; Vascular Grafting

Staphylococcus aureus is the main causal pathogen of infective endocarditis (IE), which may have distinct origins, namely, community, nosocomial, or non-nosocomial healthcare-associated (NNHCA). We report the first case of NNHCA-IE caused by methicillin-resistant S. aureus strain USA400/SCCmec IV in which the combination therapy of rifampin and vancomycin had a favorable outcome for the patient.

Topics: Adult; Anti-Bacterial Agents; Brazil; Echocardiography, Transesophageal; Endocarditis; Genotype; Health Facilities; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Molecular Typing; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Topics: Aged; Anti-Bacterial Agents; Contraindications; Daptomycin; Disease Progression; Drug Substitution; Echocardiography, Transesophageal; Endocarditis; Fatal Outcome; Fluid Therapy; Hepatic Encephalopathy; Hepatorenal Syndrome; Humans; Kidney Function Tests; Liver Transplantation; Male; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis; Vancomycin

This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Topics: Animals; Daptomycin; Endocarditis; Glycopeptides; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rabbits; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Topics: Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis; Fatal Outcome; Humans; Infant; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Anti-Bacterial Agents; Body Fluids; Community-Acquired Infections; Daptomycin; Echocardiography, Transesophageal; Endocarditis; Female; Humans; Italy; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pericardiocentesis; Rifampin; Staphylococcal Infections; Treatment Outcome

The findings of clinical and in vitro research support the theory that infective endocarditis (IE)-causing bacteria form biofilms and that biofilms negatively affect treatment outcomes. The purpose of the present study was to quantify the biofilm formation of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates obtained from patients with IE and to evaluate the in vitro activities of daptomycin and vancomycin alone and in combination with rifampin (rifampicin) or gentamicin while monitoring the isolates for the development of resistance. A high-inoculum, stationary-phase infection model of IE was used to simulate the pharmacokinetics in humans of daptomycin at 6 mg/kg of body weight/day, vancomycin at 1.25 g every 12 h (q12h) alone and in combination with rifampin at 300 mg every 8 h, and gentamicin at 1.3 mg/kg q12h. Two randomly selected clinical MRSA isolates were obtained from patients with IE; both MRSA isolates quantitatively produced biofilms. The time to bactericidal activity in the presence of daptomycin was isolate dependent but was achieved by 24 h for both MRSA isolates. Vancomycin did not achieve bactericidal activity throughout the experiment. At 24, 48, and 72 h, daptomycin-containing regimens had significantly more activity (greater declines in the mean number of CFU/g) than any of the vancomycin-containing regimens (P = 0.03). Rifampin and gentamicin antagonized or delayed the bactericidal activity of daptomycin (against MRSA B346846 for rifampin and against both isolates for gentamicin) in the first 24 h. Increases in the daptomycin and vancomycin MICs were not observed. We conclude that in an IE model of biofilm-forming MRSA, daptomycin monotherapy has better in vitro activity than daptomycin in combination with rifampin or gentamicin or any vancomycin-containing regimen studied within the first 24 h. Further investigations are needed to understand the initial delay in bactericidal activity observed when gentamicin or rifampin is combined with daptomycin.

Topics: Anti-Bacterial Agents; Biofilms; Daptomycin; Endocarditis; Gentamicins; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Vancomycin

A 73-year-old woman with endocarditis was treated with flucloxacillin and rifampicin. She already used the anticoagulant acenocoumarol because of a recent heart valve replacement. After starting rifampicin therapy the sensitivity for the acenocoumarol was reduced. The international normalised ratio (INR) did not exceed 2.0, while values of 2.5-3.5 were required. Increase of the daily dose of acenocoumarol with a factor 6 compared to the dose which resulted in a therapeutic INR before hospitalisation, proved insufficient to obtain a therapeutic INR during long-term rifampicin therapy. 21 days after rifampicin discontinuation the INR finally responded to high coumarin dosages. The breakdown of coumarins in the liver is increased by rifampicin due to induction of several isoenzymes of the cytochrome P450-system. This case illustrates that sensitivity to coumarins can be decreased profoundly even after discontinuation of rifampicin therapy. INR should be monitored closely not only at the start and discontinuation of rifampicin therapy, but also during the weeks after discontinuation of rifampicin treatment.

Topics: Acenocoumarol; Aged; Anti-Bacterial Agents; Anticoagulants; Dose-Response Relationship, Drug; Drug Interactions; Endocarditis; Female; Heart Valve Prosthesis; Humans; International Normalized Ratio; Liver; Rifampin; Time Factors

Infective endocarditis is an uncommon disease but retains a high mortality. Glycopeptides are used for patients with resistant pathogens, those allergic to penicillins or for those outside the hospital. The once daily administration of teicoplanin and its low toxicity suggest that it would be suitable for use in the long courses required for endocarditis. However, the dosage and combinations to be used require further study. A retrospective review has been made of 104 episodes of endocarditis treated with teicoplanin in 101 patients seen over 7 years. Most patients had been referred to major London hospitals following failure of medical treatment. After three loading doses of 400 mg, teicoplanin was given at a dose of 400 mg/day in combination with other antibiotics such as gentamicin. Follow up was for one year. The most common pathogens were Streptococcus sanguis (15 cases), Staphylococcus aureus (13 cases) and Staphylococcus epidermidis (10 cases). Of 80 patients febrile at the start of treatment with teicoplanin, 63 (79%) lost their fever within a median of 2 days (1-35 days). Cure without surgery was effected in 50 (48%) and 75% of patients survived. Other antibiotics, usually gentamicin or rifampicin, were used in 92 (90%) of patients. Two strains of Streptococcus spp. were said to be resistant but there was no relationship between MIC of teicoplanin and outcome. Pathogens with a high MBC tended to be more likely to resist treatment. Adverse effects resulted in the withdrawal of teicoplanin in 20 cases (19%) but most events were mild and renal deterioration occurred in only five patients. Teicoplanin was effective in the treatment of endocarditis and appeared to be safe given the severity of disease in the patients treated.

Topics: Adult; Aged; Anti-Bacterial Agents; Aortic Valve; Endocarditis; Female; Fever; Fusidic Acid; Gentamicins; Humans; London; Male; Microbial Sensitivity Tests; Middle Aged; Prostheses and Implants; Retrospective Studies; Rifampin; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus sanguis; Teicoplanin; Time Factors; Treatment Outcome

Wangiella dermatitidis is an infrequently encountered dematiacious fungus that usually causes localized infections of the skin and subcutaneous tissues. This report presents the first well-documented case of natural valve infection caused by this organism as it occurred in intravenous drug abuser. His course has been complicated by relapsing infection of two aortic prostheses and dissemination to the vertebral spine. Treatment with a combination of amphotericin B, rifampin, and ketoconazole has arrested the progression of his infection. The microbiologic features and existing clinical information regarding this fungus are reviewed and in vitro susceptibility data for the present isolate are presented.

Topics: Adult; Amphotericin B; Aortic Valve; Drug Therapy, Combination; Endocarditis; Heart Valve Diseases; Heroin Dependence; Humans; Ketoconazole; Male; Mitosporic Fungi; Mycoses; Recurrence; Reoperation; Rifampin

Antibiotic therapy of methicillin-resistant Staphylococcus epidermidis endocarditis was investigated with the rabbit endocarditis model. Time-kill studies in vitro demonstrated that gentamicin and rifampin had the most rapid early bactericidal rates. With rifampin alone, rifampin-resistant subpopulations emerged. Combinations of antibiotics with gentamicin or rifampin in vitro did not significantly alter the killing rate but prevented emergence of subpopulations resistant to the latter. In the rabbit endocarditis model, gentamicin and vancomycin were the most effective single antibiotic regimens in terms of ability to reduce the bacterial densities on cardiac valve vegetations. Five treatment regimens were equally effective, including vancomycin, gentamicin, vancomycin plus rifampin or gentamicin, and rifampin plus gentamicin. The three-drug combination of vancomycin, rifampin, and gentamicin did not significantly improve the results. Cephalothin therapy was significantly less effective than any of the regimens noted above. It was no more effective than no treatment at 2 days and was only slightly more effective at 4 days. This result with cephalothin treatment was not predicted by routine types of in vitro antibiotic susceptibility testing. Treatment of rabbits with methicillin or cephalothin was associated with an increase in the subpopulation of bacteria resistant to the respective drugs. A number of regimens show potential for therapy of these infections, including vancomycin plus rifampin or gentamicin, rifampin plus gentamicin, and vancomycin alone.

Topics: Animals; Anti-Bacterial Agents; Cephalothin; Disease Models, Animal; Drug Therapy, Combination; Endocarditis; Gentamicins; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Drug Interactions; Endocarditis; Humans; Rifampin; Warfarin

Topics: Aortic Valve; Aortic Valve Insufficiency; Chlamydia; Complement Fixation Tests; Endocarditis; Heart Valve Prosthesis; Humans; Male; Microscopy, Electron; Middle Aged; Rifampin; Tetracycline