Efficacy Of Rifampin Research Articles

Rifampin in device-related infections: Assessing the modern evidence.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Rifampin is commonly used to treat device-related infections (DRIs) due to its activity against biofilms, despite a history of limited clinical evidence to support its use. Evidence published since 2011 regarding rifampin use for DRIs is reviewed to describe the contemporary findings and ongoing considerations for rifampin use in these infections. A literature review was performed by searching PubMed and Google Scholar to identify relevant studies evaluating systemic rifampin use for the treatment of DRIs published from 2011 to 2023. References of identified studies were also screened for additional pertinent studies. Sixty-eight studies were identified, and 48 met the inclusion criteria. Rifampin efficacy was evaluated as both a primary outcome for cardiac device infections (n = 3) and prosthetic joint infections (n = 21) and as a nonprimary outcome (n = 24). Overall, the studies were primarily retrospective (n = 36) and small, with sample sizes ranging from 14 to 842 patients, and varied greatly with respect to prosthesis site, surgical intervention, pathogen, infection time frame, and antibiotic combination and duration. Efficacy outcome results varied greatly, with statistically significant evidence for the efficacy of rifampin combination in DRIs limited to a single study of prosthetic vascular graft infections and 13 studies of prosthetic joint infections. The modern literature provides conflicting results regarding the benefit and lack of benefit with rifampin combination therapy in DRIs. Additional, robust research is imperative to solidify the ongoing role of rifampin in DRIs.

Caspofungin enhances the potency of rifampin against Gram-negative bacteria.

Developing antibiotic adjuvants is an effective strategy to combat antimicrobial resistance (AMR). The envelope of Gram-negative bacteria (GNB) is a barrier to prevent the entry of antibiotics, making it an attractive target for novel antibiotic and adjuvant development. In this study, we identified Caspofungin acetate (CAS) as an antibiotic adjuvant against GNB in the repurposing screen of 3,158 FDA-approved drugs. Checkerboard assays suggested that CAS could enhance the antimicrobial activity of rifampin or colistin against various GNB strains in vitro, Moreover, Galleria mellonella larvae infection model also indicated that CAS significantly potentiated the efficacy of rifampin against multidrug-resistant Escherichia coli 72 strain in vivo. Most importantly, resistance development assay showed that CAS was less susceptible to accelerating the resistance development of drug-sensitive strain E. coli MG1655. Functional studies and RNA-seq analysis confirmed that the mechanisms by which CAS enhanced the antimicrobial activities of antibiotics were involved in permeabilizing the bacterial cell envelope, disrupting proton motive force and inhibiting bacterial biofilm formation. Additionally, it has been found that PgaC is the CAS target and enzymatic assay has confirmed the inhibition activity. Our results illustrate the feasibility of CAS as an antibiotic adjuvant against GNB, which is an alternative strategy of anti-infection.

Rifampin monotherapy for children with idiopathic infantile hypercalcemia

Idiopathic Infantile Hypercalcemia (IIH) is characterized by hypercalcemia and hypercalciuria owing to PTH-independent increases in circulating concentrations of 1,25(OH)2D. At least 3 forms of IHH can be distinguished genetically and mechanistically: infantile hypercalcemia-1 (Hypercalcemia, Infantile, 1; HCINF1) due to CYP24A1 mutations results in decreased inactivation of 1,25(OH)2D; HCINF2 due to SLC34A1 mutations results in excessive 1,25(OH)2D production; and HCINF3 in which a variety of gene variants of uncertain significance (VUS) have been identified and where the mechanism for increased 1,25 (OH)2D is unclear. Conventional management with dietary calcium and vitamin D restriction has only limited success. Induction of the P450 enzyme CYP3A4 by rifampin can provide an alternate pathway for inactivation of 1,25(OH)2D that is useful in HCINF1 and may be effective in other forms of IIH.We sought to assess the efficacy of rifampin to decrease levels of serum 1,25(OH)2D and calcium, and urinary calcium concentrations in subjects with HCINF3, and to compare the response to a control subject with HCINF1.Four subjects with HCINF3 and the control subject with HCINF1 completed the study using rifampin 5 mg/kg/day and 10 mg/kg/day each for 2 months separated by a 2-month washout period. Patients had age-appropriate intake of dietary calcium plus 200 IU vitamin D/day. Primary outcome was efficacy of rifampin to lower serum concentrations of 1,25(OH)2D. The secondary outcomes included the reduction of serum calcium, urinary calcium excretion (as random urine calcium: creatinine (ca:cr) ratio) and serum 1,25(OH)2D/PTH ratio.Rifampin was well tolerated and induced CYP3A4 at both doses in all subjects. The control subject with HCINF1 showed significant response to both rifampin doses with decreases in the serum concentration of 1,25(OH)2D and the 1,25(OH)2D/PTH ratio while the serum and urine ca:cr levels were unchanged. The four patients with HCINF3 showed reductions in 1,25(OH)2D and urinary ca:cr after 10 mg/kg/d, but hypercalcemia did not improve and there were variable responses in 1,25(OH)2D/PTH ratios. These results support further longer-term studies to clarify the usefulness of rifampin as a medical therapy for IIH.

Long-term Efficacy and Safety of Rifampin in the Treatment of a Patient Carrying a CYP24A1 Loss-of-Function Variant

Pharmacological therapy may be useful in the treatment of moderate to severe hypercalcemia in patients with infantile hypercalcemia-1 (HCINF1) due to pathogenic variants in the cytochrome P450 24 subfamily A member 1 (CYP24A1). Rifampin is an antituberculosis drug that is a potent inducer of cytochrome P450 3 subfamily A member 4 (CYP3A4), involved in an alternative catabolic pathway of vitamin D. The efficacy of rifampin in improving hypercalcemia was previously reported but many questions remain on the long-term efficacy and safety. Aim of the study is to test the long-term efficacy and safety of rifampin in a patient with HCINF1. We report clinical, biochemical and imaging features of a 23-year-old man affected by HCINF1 with moderate hypercalcemia (12.9mg/dL), symptomatic nephrolithiasis, nephrocalcinosis and impaired kidney function (eGFR 60mL/min/1.73 m2) treated with rifampin for an overall period of 24 months. Kidney, liver and adrenal function were evaluated at every follow-up visit. In 2 months, rifampin induced a normalization of serum calcium (9.6mg/dL) associated with an improvement of kidney function (eGFR 92mL/min/1.73 m2) stable during the treatment. After 15 months, rifampin was temporally withdrawn because of asthenia, unrelated to impairment of adrenal function. After three months, the timing of drug administration was shifted from the morning to the evening, obtaining the remission of asthenia. At the end of follow-up, the nephrolithiasis disappeared and the nephrocalcinosis was stable. Rifampin could represent an effective choice to induce a stable reduction of calcium levels in patients with HCINF1, with a good safety profile.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

Objectives: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). Methods: Retrospective, multicenter, cohort study of PJI by S. aureus (2003–2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. Results: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. Conclusions: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Differential effects of cotreatment of the antibiotic rifampin with host-directed therapeutics in reducing intracellular Staphylococcus aureus infection.

BackgroundChronic infection by Staphylococcus aureus drives pathogenesis in important clinical settings, such as recurrent pulmonary infection in cystic fibrosis and relapsing infection in osteomyelitis. Treatment options for intracellular S. aureus infection are limited. Rifampin, a lipophilic antibiotic, readily penetrates host cell membranes, yet monotherapy is associated with rapid antibiotic resistance and development of severe adverse events. Antibiotic cotreatment can reduce this progression, yet efficacy diminishes as antibiotic resistance develops. ML141 and simvastatin inhibit S. aureus invasion through host-directed rather than bactericidal mechanisms.ObjectiveTo determine whether cotreatment of ML141 or of simvastatin with rifampin would enhance rifampin efficacy.MethodsAssays to assess host cell invasion, host cell viability, host cell membrane permeability, and bactericidal activity were performed using the human embryonic kidney (HEK) 293-A cell line infected with S. aureus (29213) and treated with vehicle control, simvastatin, ML141, rifampin, or cotreatment of simvastatin or ML141 with rifampin.ResultsWe found cotreatment of ML141 with rifampin reduced intracellular infection nearly 85% when compared to the no treatment control. This decrease more than doubled the average 40% reduction in response to rifampin monotherapy. In contrast, cotreatment of simvastatin with rifampin failed to improve rifampin efficacy. Also, in contrast to ML141, simvastatin increased propidium iodide (PI) positive cells, from an average of 10% in control HEK 293-A cells to nearly 20% in simvastatin-treated cells, indicating an increase in host cell membrane permeability. The simvastatin-induced increase was reversed to control levels by cotreatment of simvastatin with rifampin.ConclusionTaken together, rifampin efficacy is increased through host-directed inhibition of S. aureus invasion by ML141, while efficacy is not increased by simvastatin. Considerations regarding novel therapeutic approaches may be dependent on underlying differences in pharmacology.

Post-exposure prophylaxis (PEP) efficacy of rifampin, rifapentine, moxifloxacin, minocycline, and clarithromycin in a susceptible-subclinical model of leprosy.

BackgroundSubclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials.Methodology/Principal findingsAthymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation.Conclusions/SignificanceThe delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3–4 months) and late (8–9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.

Safety and Efficacy of Rifampin or Isoniazid Among People With Mycobacterium tuberculosis Infection and Living With Human Immunodeficiency Virus or Other Health Conditions: Post Hoc Analysis of 2 Randomized Trials.

The safety and efficacy of rifampin among people living with human immunodeficiency virus (PLHIV) or other health conditions is uncertain. We assessed completion, safety, and efficacy of 4 months of rifampin vs 9 months of isoniazid among PLHIV or other health conditions. We conducted post hoc analysis of 2 randomized trials that included 6859 adult participants with Mycobacterium tuberculosis infection. Participants were randomized 1:1 to 10 mg/kg/d rifampin or 5 mg/kg/d isoniazid. We report completion, drug-related adverse events (AE), and active tuberculosis incidence among people living with HIV; with renal failure or receiving immunosuppressants; using drugs or with hepatitis; with diabetes mellitus; consuming >1 alcoholic drink per week or current/former smokers; and with no health condition. Overall, 270 (3.9%) people were living with HIV (135 receiving antiretroviral therapy), 2012 (29.3%) had another health condition, and 4577 (66.8%) had no condition. Rifampin was more often or similarly completed to isoniazid in all populations. AEs were less common with rifampin than isoniazid among PLHIV (risk difference, -2.1%; 95% confidence interval [CI], -5.9 to 1.6). This was consistent for others except people with renal failure or on immunosuppressants (2.1%; 95% CI, -7.2 to 11.3). Tuberculosis incidence was similar among people receiving rifampin or isoniazid. Among participants receiving rifampin living with HIV, incidence was comparable to those with no health condition (rate difference, 4.1 per 1000 person-years; 95% CI, -6.4 to 14.7). Rifampin appears to be safe and as effective as isoniazid across many populations with health conditions, including HIV. NCT00170209; NCT00931736.

Effect of the nanoliposomal formulations of rifampin and N-acetyl cysteine on staphylococcus epidermidis biofilm

Objective(s): Staphylococcus epidermidis is a common cause of medical device-associated infections due to biofilm formation, and its elimination is extremely challenging. Although rifampin efficacy against S. epidermidis biofilms has been confirmed, its use as a single agent may lead to resistance. As such, it is assumed that the combination of rifampin and N-acetylcysteine (NAC) could exert additive effects as a mucolytic agent. The present study aimed to use a liposomal system for the delivery of these compounds to bacterial biofilm.Materials and Methods: Liposomal formulations were prepared using the dehydration-rehydration method and characterized in terms of the size, zeta potential, and encapsulation efficacy. In addition, the ability of various formulations in the eradication of bacterial biofilm and inhibition of biofilm formation was assessed based on the optical density ratio. Results: The zeta potential of the liposomes was positive, and the mean size of these liposomal formulations was less than 200 nanometers. Liposomal rifampin was the most effective formulation against S. epidermidis, and the anti-biofilm activity of most of the formulations was concentration-dependent and time-dependent.Conclusion: According to the results, the rifampin-loaded liposomes were effective against S. epidermidis biofilm formation.

Rifampin- or Capreomycin-Induced Remodeling of the Mycobacterium smegmatis Mycolic Acid Layer Is Mitigated in Synergistic Combinations with Cationic Antimicrobial Peptides.

The mycobacterial cell wall affords natural resistance to antibiotics. Antimicrobial peptides (AMPs) modify the surface properties of mycobacteria and can act synergistically with antibiotics from differing classes. Here, we investigate the response of Mycobacterium smegmatis to the presence of rifampin or capreomycin, either alone or in combination with two synthetic, cationic, α-helical AMPs that are distinguished by the presence (D-LAK120-HP13) or absence (D-LAK120-A) of a kink-inducing proline. Using a combination of high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) metabolomics, diphenylhexatriene (DPH) fluorescence anisotropy measurements, and laurdan emission spectroscopy, we show that M.smegmatis responds to challenge with rifampin or capreomycin by substantially altering its metabolism and, in particular, by remodeling the cell envelope. Overall, the changes are consistent with a reduction of trehalose dimycolate and an increase of trehalose monomycolate and are associated with increased rigidity of the mycolic acid layer observed following challenge by capreomycin but not rifampin. Challenge with D-LAK120-A or D-LAK120-HP13 induced no or modest changes, respectively, in mycomembrane metabolites and did not induce a significant increase in the rigidity of the mycolic acid layer. Furthermore, the response to rifampin or capreomycin was significantly reduced when these were combined with D-LAK120-HP13 and D-LAK120-A, respectively, suggesting a possible mechanism for the synergy of these combinations. The remodeling of the mycomembrane in M.smegmatis is therefore identified as an important countermeasure deployed against rifampin or capreomycin, but this can be mitigated and the efficacy of rifampin or capreomycin potentiated by combining the drug with AMPs.IMPORTANCE We have used a combined NMR metabolomics/biophysical approach to better understand differences in the mechanisms of two closely related antimicrobial peptides, as well as the response of the model organism Mycobacterium smegmatis to challenge with first- or second-line antibiotics used against mycobacterial pathogens. We show that, in addition to membrane damage, the triggering of oxidative stress may be an important part of the mechanism of action of one AMP. The metabolic shift that accompanied rifampin and, particularly, capreomycin challenge was associated with modest and more dramatic changes, respectively, in the mycomembrane, providing a rationale for how the response to one antibiotic may affect bacterial penetration and, hence, the action of another. This study presents the first insights into how antimicrobial peptides may operate synergistically with existing antibiotics whose efficacy is waning or sensitize MDR mycobacteria and/or latent mycobacterial infections to them, prolonging the useful life of these drugs.

Rifampin vs. rifapentine: what is the preferred rifamycin for tuberculosis?

ABSTRACTIntroduction: One-third of the world’s population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment?Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them.Expert commentary: Rifampin has shorter half-life, higher MIC against M.tb, lower protein binding, and better distribution into cavitary contents than rifapentine. Drug interactions for the two drugs maybe similar in magnitude. For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care. Safety profile of rifampin is better-described; adverse events differ somewhat for the two drugs. The registered once-weekly rifapentine regimen is inadequate, but higher doses of either drugs may shorten the treatment duration required for effective management of TB. Results of clinical trials evaluating high-dose rifamycin regimens are eagerly awaited.

Antibacterial efficacy of rifampin loaded solid lipid nanoparticles against Staphylococcus epidermidis biofilm

ObjectiveThe aim of the present study was to assess the in vitro anti-biofilm activities of solid lipid nanoparticles (SLN) loaded with rifampin against biofilm-producing Staphylococcus epidermidis. MethodsSLN were prepared and characterized for size, zeta potentials and encapsulation efficacy. The morphological and thermal properties of formulation were evaluated by TEM imagining and DSC analysis. The anti-biofilm activity of different formulations was assessed at different incubation times and concentrations by crystal violet (CV) and viable biofilm count methods. ResultsThe zeta potentials, particle sizes and encapsulation efficiencies of final formulations were 17 ± 0.7 mV, 101 ± 4.7 nm and approximately 70%; respectively. Rifampin-SLN was able to reduce the biomass of biofilm at time- and concentration-dependent manner. According to biofilm count results, the Rifampin-SLN was more effective for removal of the bacteria with respect to free rifampin. ConclusionThe results of this study highlight the advantages and efficiency of Rifampin-SLN in biofilm eradication.

Predictors of treatment outcome in prosthetic joint infections treated with prosthesis retention.

The reported success rates of debridement, antibiotics, and implant retention (DAIR) for prosthetic joint infections (PJIs) vary widely. Several risk factors have been described for treatment failure, but they vary between studies. The purpose of this study was to evaluate the predictors of DAIR failure in PJI treatment and to assess the efficacy of rifampin combined with ciprofloxacin versus rifampin combined with other antibiotics in staphylococcal PJIs. Patients with PJI that underwent DAIR for the first time between February 2001 and August 2009 were identified retrospectively in the hospital's patient databases. A total of 113 PJI cases with early postoperative or acute haematogenous PJI were followed for up to two years from the start of treatment. In univariate analysis, variables significantly associated with treatment failure were acute haematogenous infections (p = 0.022), leucocyte count at admission > 10 × 10(9)/l (p < 0.01), pain in the joint (p < 0.01), and ineffective empirical antibiotics (p < 0.01). In a multivariate Cox model, leucocyte count > 10 × 10(9)/l and ineffective empirical antibiotics were significant risk factors for failure. Compared to rifampin-ciprofloxacin, the hazard ratio (HR) for treatment failure was significantly increased in the rifampin-other antibiotics group (HR 6.0, 95% CI 1.5-28.8, p = 0.014) and the group treated without rifampin (HR 14.4, 95% CI 3.1-66.9, p < 0.01). Rifampin-ciprofloxacin combination therapy was significantly more effective than rifampin combined with other antibiotics. Effective empirical antibiotics are essential for successful PJI treatment.

The efflux pump inhibitor timcodar improves the potency of antimycobacterial agents.

Previous studies indicated that inhibition of efflux pumps augments tuberculosis therapy. In this study, we used timcodar (formerly VX-853) to determine if this efflux pump inhibitor could increase the potency of antituberculosis (anti-TB) drugs against Mycobacterium tuberculosis in in vitro and in vivo combination studies. When used alone, timcodar weakly inhibited M. tuberculosis growth in broth culture (MIC, 19 μg/ml); however, it demonstrated synergism in drug combination studies with rifampin, bedaquiline, and clofazimine but not with other anti-TB agents. When M. tuberculosis was cultured in host macrophage cells, timcodar had about a 10-fold increase (50% inhibitory concentration, 1.9 μg/ml) in the growth inhibition of M. tuberculosis and demonstrated synergy with rifampin, moxifloxacin, and bedaquiline. In a mouse model of tuberculosis lung infection, timcodar potentiated the efficacies of rifampin and isoniazid, conferring 1.0 and 0.4 log10 reductions in bacterial burden in lung, respectively, compared to the efficacy of each drug alone. Furthermore, timcodar reduced the likelihood of a relapse infection when evaluated in a mouse model of long-term, chronic infection with treatment with a combination of rifampin, isoniazid, and timcodar. Although timcodar had no effect on the pharmacokinetics of rifampin in plasma and lung, it did increase the plasma exposure of bedaquiline. These data suggest that the antimycobacterial drug-potentiating activity of timcodar is complex and drug dependent and involves both bacterial and host-targeted mechanisms. Further study of the improvement of the potency of antimycobacterial drugs and drug candidates when used in combination with timcodar is warranted.

The effect of nanoliposomal formulations on Staphylococcus epidermidis biofilm

Objective: The aim of the present study was to assess the in vitro antimicrobial activities of nanoliposomal formulations loaded with vancomycin or/and rifampin against the biofilm formed by Staphylococcus epidermidis at 37 °C under aerobic condition.Materials and methods: Liposomal formulations were prepared by dehydration-rehydration (DRV) method and characterized for size, zeta potential and encapsulation efficacy. The ability of different formulations on eradication of bacterial biofilm was assessed through optical density ratio (ODr) and the results implicate higher survival rates of S. epidermidis on biofilm. Positive control was defined as an ODr = 1.0.Results: The zeta potential of anionic, cationic and PEGylated liposomes was −35 ± 2, 35 ± 1 and 27 ± 2 mV whereas the mean sizes of these liposomal formulations were 145 ± 4, 134 ± 1 and 142 ± 6 nm, respectively. Encapsulation efficacy of rifampin and vancomycin was more than 60% and about 25%, respectively. Cationic liposomal rifampin lowered the ODr to 0.61 and was the most effective formulations against S. epidermidis biofilm (p < 0.001). The antibiofilm activity of liposomal formulations was concentration- and time-dependent manner.Conclusion: The results of this study showed that rifampin-loaded liposomes were effective against bacterial biofilm.

Effect of rifampin in combination with allogeneic, alloplastic, and heterogenous bone grafts on bone regeneration in rat tibial bone defects

PurposeThe aim of this study was to evaluate the efficacy of rifampin with allogeneic, alloplastic, and heterogeneous bone graft substitutes on osteogenesis of experimentally created bone defects in rat tibias. Materials and methodsTwenty-eight male Wistar albino rats were used in this study. In each animal, two bone defects (10mm length×3mm width×2mm depth) were created in the left and right tibias, respectively. The animals were divided into four groups. In Group 1, the right defects were irrigated with rifampin alone, and the left defects were irrigated with sterile saline alone. In Group 2, the right defects were filled with rifampin and allogeneic bone graft, and the left defects were filled with allogeneic bone graft alone. In Group 3, the right defects were treated with rifampin and alloplastic bone graft, and the left defects were filled with alloplastic bone graft alone. In Group 4, the right defects were filled with rifampin and heterogeneous bone graft, and the left defects were filled with heterogeneous bone graft alone. ResultsThe animals were sacrified on the 21st postoperative day. Histopathological analysis of samples was performed to evaluate the process of bone regeneration and the presence of spongeous bone, cortex bone, and bone marrow. Bone union (p=0.023) and spongeous bone (p=0.030) values were higher in Group 1A (rifampin alone) than those in Group 1B (saline alone). Bone union (p<0.001) and spongeous bone (p<0.001) values in Group 2B (allograft+saline) were higher than those in Group 2A (allograft+rifampin). These differences were statistically significant. ConclusionsTopical rifampin can accelerate the bone repair process, but the combination of rifampin and allogeneic bone grafts can also reduce new bone formation in osseous defects. Further studies involving long-term follow-up with a larger number of cases and different antibiotic agents should be conducted. These will provide additional data regarding new bone formation, especially in contaminated bone defects, resulting from use of antibiotic-supplemented bone grafts.

Cost-effectiveness of rifampin for 4 months and isoniazid for 6 months in the treatment of tuberculosis infection

To assess the cost-effectiveness ratio of rifampin for 4 months and isoniazid for 6 months in contacts with latent tuberculosis infection. The cost was the sum of the cost of treatment with isoniazid for 6 months or with rifampin for 4 months of all contacts plus the cost of treatment of cases of tuberculosis not avoided. The effectiveness was the number of cases of tuberculosis avoided with isoniazid for 6 months or with rifampin for 4 months. When the cost with one schedule was found to be cheaper than the other and a greater number of tuberculosis cases were avoided, this schedule was considered dominant. The efficacy adopted was 90% for rifampin for 4 months and 69% for isoniazid for 6 months. A sensitivity analysis was made for efficacies of rifampin for 4 months of 80%, 69%, 60% and 50%. Of the 1002 patients studied, 863 were treated with isoniazid for 6 months and 139 with rifampin for 4 months The cost-effectiveness ratio with isoniazid for 6 month was € 19759.48/avoided case of tuberculosis and € 8736.86/avoided case of tuberculosis with rifampin for 4 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies from 60%. Rifampin for 4 months was more cost-effective than isoniazid for 6 months.

Cost-effectiveness of rifampin for 4 months and isoniazid for 9 months in the treatment of tuberculosis infection

The purpose of this study was to evaluate the cost-effectiveness of the strategy of controlling the contacts of tuberculosis patients with latent tuberculosis infection by means of treatment with rifampin for 4 months or isoniazid for 9 months. The cost was the sum of the cost of treating latent tuberculosis infection in all contacts plus the cost of treating tuberculosis in whom the disease was not avoided. The effectiveness was expressed as cases avoided. The efficacy adopted was 90 % for rifampin for 4 months and 93 % for isoniazid for 9 months. We carried out a sensitivity analysis for efficacies of rifampin for 4 months of 80 %, 75 %, 69 % and 65 %. Of the 1,002 patients studied, 139 were treated with rifampin for 4 months and 863 were treated with isoniazid for 9 months. The cost-effectiveness was <euro>436,842.83/50 cases avoided with rifampin for 4 months and <euro>692,164.42/40 cases avoided with isoniazid for 9 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies of 75 % or greater. The cost-effectiveness analysis favoured the use of rifampin for 4 months when its efficacy was 75 % or greater.

Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains

The objective of this work was to evaluate the efficacy of rifampin, and its combinations with imipenem or sulbactam, in an experimental pneumonia model caused by two panresistant Acinetobacter baumannii strains (HUVR99 and HUVR113). Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) (μg/ml) of the strains were rifampin 128/>128 for both strains, imipenem 128/>256 and 256/>256 for HUVR99 and HUVR113, respectively, and sulbactam >256/>256 for both strains. In time-kill studies, at MICs, rifampin was bactericidal for both strains and sulbactam against the HUVR99 strain. Rifampin plus imipenem or sulbactam, at the MIC or mice C (max), were synergistic. In vivo, against HUVR99 and HUVR113, rifampin (73% and 40%) and its combinations improved the survival with respect to the control group (20% and 0%, p < 0.05), respectively. Rifampin (87% and 46%) and its combinations improved the sterilization of blood cultures with respect to the control groups (0%, p < 0.05). In regard to the bacterial clearance from lungs, rifampin (2.57 ± 2.47 and 5.35 ± 3.03 log(10) cfu/g) and its combinations with imipenem or sulbactam diminished the bacterial lung concentration with respect to the control group (10.89 ± 3.00 and 11.86 ± 0.49, p < 0.05) with both strains. In conclusion, rifampin alone or associated to imipenem or sulbactam were effective for the treatment of murine pneumonia caused by selected panresistant A. baumannii strains.

Comparative study of doxycycline and rifampin therapeutic effects in subclinical phase of canine monocytic ehrlichiosis

A double-blind randomized controlled trial was designed for a 6-month period to compare the efficacy of rifampin versus doxycycline during the subclinical phase of canine monocytic ehrlichiosis. Ten naturally Ehrlichia canis-infected dogs with anti-E. canis immunofluorescent antibodies ranging 1/80 to 1/1,280 were divided in two therapeutic groups. The first treatment group was scheduled by prescription of 10 mg/kg/d doxycycline for 28 days. The second group treated with rifampin 15 mg/kg every 12 h for 1 week. All treated dogs were examined periodically during the 6-month period posttreatment. Alterations in anti-E. canis immunofluorescent antibodies and clinicopathologic parameters were compared before and after treatment to evaluate the efficacy of therapeutic regimens. According to the initial antibody titer, no significant difference was observed in any of the five cases in each group. A substantial main effect of time on mean PCV, thrombocyte and erythrocyte count, and gradual resolution of hyperglobulinemia was significantly observed in all treated animals (p 0.05). Similar clinicopathologic response was observed in both treated groups; thus, it was concluded that rifampin and doxycycline are equally effective for treatment of canine monocytic ehrlichiosis.