Treatment and Toxicity Considerations in Tuberculosis: A Narrative Review.

Tuberculosis remains one of the most significant bacterial infections plaguing the medical community worldwide. The bacteria Mycobacterium tuberculosis retains the ability to manifest as an active infection, latent infection, miliary infection, or reactivation of latent infections in times of immunosuppression. Therefore, the medication regimen to treat the condition revolves around four medications, each with a mechanism that targets a different part of the bacteria. Isoniazid weakens the cell wall but produces neuropathy and hepatotoxicity as side effects. Rifampin interrupts protein synthesis but creates the opportunity for many drug-to-drug interactions and red-orange discolorations as side effects. Pyrazinamide is poorly understood, but it is believed to acidify the internal environment of the bacteria, with gout exacerbations and arthralgias as major side effects. Ethambutol also works as a bacteriostatic medication to interrupt the cell membrane; however, its mechanism is poorly understood. The most concerning side effect is optic neuropathy. The unfavorable side effect profile for tuberculosis treatment may contribute to the higher rates of medication noncompliance with therapy and needs to be addressed in the future.

Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates.

Infections due to drug-resistant Acinetobacter baumannii strains are increasing and cause significant morbidity and mortality, especially in hospitalized and critically ill patients. A. baumannii rapidly develops resistance to numerous antibiotics, and antibiotics traditionally used against this deadly pathogen have been failing in recent years, highlighting the need to identify new treatment strategies. Treatment options that have shown promise include revisiting common antibiotics not typically used against A. baumannii, evaluating new antibiotics recently introduced to market, and identifying combinations of antibiotics that display synergistic interactions. In this study, we characterized the antibiotic susceptibility profiles of extensively (XDR) and pandrug-resistant (PDR) A. baumannii patient isolates. We examined the potency of 22 standard-of-care antibiotics and the newer antibiotics eravacycline, omadacycline, and plazomicin against these strains. Furthermore, we examined combinations of these antibiotics against our collection to identify synergistic effects. We found that this collection is highly resistant to most or all standard-of-care antibiotics, except for minocycline and rifampin. We show that eravacycline and omadacycline are effective against these strains based on minimum inhibitory concentrations. We also identified two highly effective combinations, cefepime and amikacin and cefepime and ampicillin-sulbactam, which exhibited high rates of synergy against this collection. This information is valuable in our battle against highly drug resistant and virtually untreatable A. baumannii infections.

Reassessment of the genetic basis of natural rifampin resistance in the genus Rickettsia.

Rickettsia, a genus of obligate intracellular bacteria, includes species that cause significant human diseases. This study challenges previous claims that the Leucine-973 residue in the RNA polymerase beta subunit is the primary determinant of rifampin resistance in Rickettsia. We investigated a previously untested Rickettsia species, R. lusitaniae, from the Transitional group and found it susceptible to rifampin, despite possessing the Leu-973 residue. Interestingly, we observed the conservation of this residue in several rifampin-susceptible species across most Rickettsia phylogenetic groups. Comparative genomics revealed potential alternative resistance mechanisms, including additional amino acid variants that could hinder rifampin binding and genes that could facilitate rifampin detoxification through efflux pumps. Importantly, the evolutionary history of Rickettsia genomes indicates that the emergence of natural rifampin resistance is phylogenetically constrained within the genus, originating from ancient genetic features shared among a unique set of closely related Rickettsia species. Phylogenetic patterns appear to be the most reliable predictors of natural rifampin resistance, which is confined to a distinct monophyletic subclade known as Massiliae. The distinctive features of the RNA polymerase beta subunit in certain untested Rickettsia species suggest that R. raoultii, R. amblyommatis, R. gravesii, and R. kotlanii may also be naturally rifampin-resistant species.

An open-label study to explore the optimal design of CYP3A drug-drug interaction clinical trials in healthy Chinese people.

A drug-drug interaction (DDI) trial of cytochrome P450 3A (CYP3A) is a necessary part of early-phase trials of drugs mainly metabolized by this enzyme, but CYP3A DDI clinical trials do not have a standard design, especially for Chinese people. We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three-cycle, self-controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24 h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations of midazolam and 1-hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21-fold based on maximum plasma concentration (Cmax), 8.37-fold based on area under the curve Pharmacology Research & Perspectives for review only from zero to the time point (AUC0-t), and 11.22-fold based on area under the curve from zero to infinity (AUC0-∞). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7 days decreased the plasma concentration of midazolam ~0.27-fold based on Cmax, ~0.18-fold based on AUC0-t, and ~0.18-fold based on AUC0-∞. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14 days. This study showed that itraconazole pretreatment for 3 days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7 days could induce near-maximal CYP3A levels.

Brucellosis-induced bilateral avascular necrosis of the hip joints in a middle-aged Iranian woman with refractory intolerance to medications: A case report.

INTRODUCTION: Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals. Brucellosis is highly prevalent in Iran, with Brucella melitensis biovar 1 being the primary causative agent. Musculoskeletal symptoms, including spondylitis, sacroiliitis, and peripheral arthritis, are common in brucellosis patients, but avascular necrosis of the hip joint is extremely rare. CASE PRESENTATION: This case report presents a middle-aged woman from Iran with untreated brucellosis infection, who developed rapidly progressing avascular necrosis affecting both hip joints. The patient's social history did not indicate any use of tobacco or alcohol. Furthermore, there was no indication of any traumatic events affecting the patient's hip joints. The patient's family history did not reveal any rheumatologic disorders, and the patient had not been diagnosed with or reported using immune suppressant medications. Laboratory results confirmed that the patient was not diagnosed with sickle cell anemia. The patient had been intolerant to the prescribed medications, Rifampin and Doxycycline. Initially, she presented with severe bilateral hip pain, anorexia, vomiting, periodic chills and fever, myalgia, and night sweats. Pelvis X-ray confirmed bilateral hip avascular necrosis, and total hip arthroplasty was scheduled but subsequently canceled due to persistent brucellosis infection. Physical examination revealed limited hip motion, pain, and inability to bear weight. Laboratory tests indicated leukocytosis, elevated levels of CRP, and high titers on Wright and 2ME tests. Intravenous Ciprofloxacin was initiated, and further investigations were scheduled. DISCUSSION: Osteoarticular complications are common in individuals with brucellosis. The sacroiliac joints are affected in 80 % of cases, while the spinal joints are affected in 50 %. Brucella-induced arthritis can be found in over 50 % of patients, with the lower limb joints being the most commonly affected. Failure to diagnose and treat hip arthritis caused by brucellosis promptly can lead to severe complications, including dislocation and avascular necrosis of the femoral head. Avascular necrosis is a condition where bone tissue dies due to compromised blood supply. It often remains asymptomatic initially and is usually found incidentally during radiographic imaging. Osteonecrosis of the femoral head can manifest as Legg-Calve-Perthes disease or as a complication of other medical conditions. Various factors can contribute to avascular necrosis, including hip dislocation or fracture, prolonged use of certain medications, excessive alcohol consumption, and certain medical conditions. Magnetic resonance imaging is considered the standard method for diagnosing avascular necrosis. Delay in diagnosing and treating brucellosis can result in permanent bone complications. CONCLUSION: Brucellosis, a disease prevalent in endemic regions, should be considered as a cause of severe hip pain and other vague symptoms. Timely diagnosis and management are important, especially for high-risk patients with other health conditions and poor drug compliance, to prevent complications such as avascular necrosis.

Pharmacokinetics of standard versus high-dose rifampin for tuberculosis preventive treatment: A sub-study of the 2R2 randomized controlled trial.

BACKGROUND: Pharmacokinetic data of rifampin, when used for tuberculosis preventive treatment (TPT) are not available. We aimed to describe the pharmacokinetics of rifampin used for TPT, at standard and higher doses, and to assess predictors of rifampin exposure. METHODS: A pharmacokinetic sub-study was performed in Bandung, Indonesia among participants in the 2R2 randomized trial, which compared TPT regimens of 2 months of high-dose rifampin at 20 mg/kg/day (2R20) and 30 mg/kg/day (2R30), with 4 months of standard-dose rifampin at 10 mg/kg/day (4R10) in adolescents and adults. Intensive pharmacokinetic sampling was performed after 2-8 weeks of treatment. Pharmacokinetic parameters were assessed non-compartmentally. Total exposure (AUC0-24) and peak concentration (Cmax) between arms were compared using one-way ANOVA and Tukey's post-hoc tests. Multivariable linear regression analyses were used to assess predictors of AUC0-24 and Cmax. RESULTS: We enrolled 51 participants in this study. In the 4R10, 2R20, and 2R30 arms, the geometric mean AUC0-24 was 68.0, 186.8, and 289.9 h⋅mg/L, and Cmax was 18.4, 36.7, and 54.4 mg/L, respectively; high interindividual variabilities were observed. Compared with the 4R10 arm, AUC0-24 and Cmax were significantly higher in the 2R20 and 2R30 arms (P < 0.001). Drug doses, body weight, and female sex were predictors of higher rifampin AUC0-24 and Cmax (P < 0.05). AUC0-24 and Cmax values were much higher than those previously reported in persons with TB disease. CONCLUSIONS: Doubling and tripling the rifampin dose led to three- and four-fold higher exposure compared to standard dose. Pharmacokinetic/pharmacodynamic modelling and simulations are warranted to support trials of shortening the duration of TPT regimens with high-dose rifampin.

Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants.

Immunocompromised patients are susceptible to fungal infections, and drug-drug interactions with antifungals may occur due to concomitant medications. Fosmanogepix [FMGX; active moiety manogepix (MGX)] targets glycosylphosphatidylinositol-anchored mannoprotein synthesis and maturation, essential for fungal virulence. This phase 1, fixed-sequence study in healthy participants evaluated the effect of strong CYP3A4 inhibitor itraconazole [Cohort 1 (n = 18); FMGX 500 mg intravenous (IV) twice a day (BID )+ itraconazole 200 mg oral once a day (QD)] and pan-CYP inducer rifampin [Cohort 2 (n = 18); FMGX 1,000 mg IV BID + rifampin 600 mg oral QD] on the pharmacokinetics of FMGX and MGX. In cohort 1, geometric mean (GM) MGX Cmax, AUC0-t, and AUCinf were almost similar with and without itraconazole administration. In Cohort 2, GM MGX Cmax was slightly lower and AUC0-t and AUCinf were significantly lower after rifampin administration, with the least squares GM ratio associated 90% confidence intervals (CIs) below 80 - 125% (no effect window). No deaths, serious adverse events (SAEs), or FMGX-related withdrawals were reported. In both cohorts, a total of 188 AEs (n = 30; 186 mild; two moderate) were reported. In all, 37 of 188 AEs (n = 12) were considered FMGX related (most frequent: headache, nausea, and hot flush). Administration of FMGX alone and with itraconazole or rifampin was safe and well tolerated. A strong CYP3A4 inhibitor had no effect on FMGX or MGX exposure. A strong pan-CYP inducer had no effect on FMGX exposure but demonstrated ~45% decrease in MGX exposure. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04166669 and with EudraCT as number 2019-003586-17.

Traditional cheese consumption leading to hemodialysis induced by rifampin treatment: A case report.

This case report details the journey of a 51-year-old man residing in a remote Iranian village, involved in livestock rearing, who was hospitalized due to Brucellosis contracted from consuming traditional cheese and dairy products. Initially treated with doxycycline and rifampin, complications arose during antituberculosis therapy, with the patient developing symptoms of nausea, vomiting, and edema alongside renal function deterioration necessitating medication cessation. Subsequent manifestations of proteinuria, toxic hepatitis, and nephrotic syndrome prompted renal biopsy, revealing drug-induced glomerular and tubular damage. Swift cessation of rifampicin, combined with prednisolone therapy, led to symptom amelioration, resulting in the cessation of dialysis and the patient's discharge within three weeks. This case underscores the intricate relationship between traditional cheese consumption, medication-induced renal complications, and the importance of timely intervention and appropriate management in achieving a successful patient outcome.

Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

Effects of Quinidine or Rifampin Co-administration on the Single-Dose Pharmacokinetics and Safety of Rilzabrutinib (PRN1008) in Healthy Participants.

This open-label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug-drug interaction between rilzabrutinib and quinidine (an inhibitor of P-glycoprotein [P-gp] and CYP2D6) or rifampin (an inducer of CYP3A and P-gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash-out period, after co-administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0-∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P-gp.

Integrative Inducer Intervention and Transcriptomic Analyses Reveal the Metabolism of Paralytic Shellfish Toxins in Azumapecten farreri.

Paralytic shellfish toxins (PSTs) are widely distributed neurotoxins, and the PST metabolic detoxification mechanism in bivalves has received increasing attention. To reveal the effect of phase I (cytochrome P450)-II (GST)-III (ABC transport) metabolic systems on the PST metabolism in Azumapecten farreri, this study amplified stress on the target systems using rifampicin, dl-α-tocopherol, and colchicine; measured PST levels; and conducted transcriptomic analyses. The highest toxin content reached 1623.48 µg STX eq/kg in the hepatopancreas and only 8.8% of that in the gills. Inducer intervention significantly decreased hepatopancreatic PST accumulation. The proportional reductions in the rifampicin-, dl-α-tocopherol-, and colchicine-induced groups were 55.3%, 50.4%, and 36.1%, respectively. Transcriptome analysis showed that 11 modules were significantly correlated with PST metabolism (six positive/five negative), with phase I CYP450 and phase II glutathione metabolism significantly enriched in negatively correlated pathways. Twenty-three phase I-II-III core genes were further validated using qRT-PCR and correlated with PST metabolism, revealing that CYP46A1, CYP4F6, GSTM1, and ABCF2 were significantly correlated, while CYP4F11 and ABCB1 were indirectly correlated. In conclusion, phase I-II-III detoxification enzyme systems jointly participate in the metabolic detoxification of PSTs in A. farreri. This study provides key data support to profoundly elucidate the PST metabolic detoxification mechanism in bivalves.

Nanoformulated meloxicam and rifampin: inhibiting quorum sensing and biofilm formation in Pseudomonas aeruginosa.

Background: We aimed to investigate the simultaneous effects of meloxicam and rifampin nanoformulations with solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) substrates on inhibiting the quorum-sensing system of Pseudomonas aeruginosa and preventing biofilm formation by this bacterium. Methods: Antimicrobial activity of rifampin and meloxicam encapsulated with SLNs and NLCs against P. aeruginosa PAO1 was assessed by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: The SLN formulation was associated with lower doses for the MIC and minimum bactericidal concentration in comparison to NLC. Moreover, our results demonstrated that both nanoformulations were able to produce 100% inhibition of the biofilm formation of P. aeruginosa PAO1. Conclusion: All these findings suggest that meloxicam and rifampin encapsulated with SLNs could be the most effective formulation against P. aeruginosa.

Cost-effectiveness of interferon-γ release assay for screening of latent tuberculosis infection in individuals with schizophrenia.

Schizophrenia is recognized as a significant risk factor for tuberculosis (TB). This study aimed to evaluate the effectiveness and cost-effectiveness of interferon-γ release assay (IGRA) with preventive treatment for screening of latent tuberculosis infection (LTBI) in individuals with schizophrenia. A state transition model was developed from a healthcare payer perspective on a lifetime horizon. Ten strategies were compared by combining two different tests for LTBI, i.e. IGRA and tuberculin skin test (TST), and five different preventive treatments, i.e. 9-month isoniazid (9H), 3-month isoniazid and rifapentine (3HP) by directly observed therapy, 3HP by self-administered therapy, 3-month isoniazid and rifampin (3RH), and 4-month rifampin (4R). The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, drug-sensitive tuberculosis (DS-TB) cases, and TB-related deaths. For both bacillus Calmette-Guérin (BCG)-vaccinated and non-BCG-vaccinated individuals, IGRA with 4R was the most cost-effective and TST with 3RH was the least effective. Among schizophrenic individuals in Japan, IGRA with 4R saved US$17.8 million, increased 58,981 QALYs and 935 LYs, and prevented 222 DS-TB cases and 75 TB-related deaths compared with TST with 3RH. In individuals with schizophrenia, IGRA with 4R is recommended for LTBI screening with preventive treatment to reduce costs, morbidity, and mortality from TB.

Efeitos do adalimumabe, clindamicina e/ou rifampicina no tratamento da hidradenite supurativa: um protocolo de revisão sistemática / Effects of adalimumab, clindamycin, and/or rifampicin in the treatment of hidradenitis suppurativa: a systematic review protocol

OBJETIVO: Avaliar a efetividade, segurança, níveis de dor e qualidade de vida associados ao uso de adalimumabe, clindamicina e/ou rifampicina no tratamento da hidradenite supurativa. MÉTODO: Serão incluídos estudos do tipo coorte prospectiva e retrospectiva, ensaios clínicos randomizados e de equivalência, bem como análises econômicas realizadas com adultos diagnosticados com hidradenite supurativa, que tenham utilizado pelo menos uma das seguintes alternativas terapêuticas: adalimumabe, clindamicina ou rifampicina. Os estudos devem abordar um ou mais desfechos, tais como contagem de abscessos e/ou nódulos, presença de nódulos inflamatórios, níveis de dor, qualidade de vida, segurança e custos. As bases de dados consultadas serão: Medical Literature Analysis and Retrieval System Online (MEDLINE, Interface OVID), Excerpta Medica DataBASE (EMBASE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL, interface EBSCO), Psychological Abstracts (PsycINFO, interface EBSCO), Web of Science (WoS) e Source-Neutral Abstract and Citation Database (Scopus). Os processos de triagem, seleção e extração serão conduzidos por pesquisadores independentes e previamente treinados. O risco de viés será avaliado por meio dos instrumentos Risk of Bias 2.0 e ROBINS-I. Os resultados serão combinados em uma síntese qualitativa e quantitativa, com a realização de análises de especificidade e subgrupos.

OBJECTIVE: To evaluate the efficacy, safety, pain, and quality of life associated with the use of adalimumab, clindamycin, and/or rifampicin in the treatment of hidradenitis suppurativa. METHOD: Prospective and retrospective cohort studies randomized clinical trials and equivalence studies, and economic analyses, conducted in adults diagnosed with hidradenitis suppurativa who have used at least one of the following therapeutic alternatives: adalimumab, clindamycin, or rifampicin, will be included. Studies should address one or more outcomes such as abscess and/or nodule counts, presence of inflammatory nodules, pain levels, quality of life, safety, and cost. Databases consulted will include Medical Literature Analysis and Retrieval System Online (MEDLINE, OVID interface), Excerpta Medica DataBASE (EMBASE), Latin American and Caribbean Literature in Health Sciences (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO interface), Psychological Abstracts (PsycINFO, EBSCO interface), Web of Science (WoS), and Source-Neutral Abstract and Citation Database (Scopus). Screening, selection, and extraction processes will be conducted by independent and previously trained researchers. The risk of bias will be assessed using the Risk of Bias 2.0 and ROBINS-I tools. Results will be summarized in a qualitative and quantitative synthesis, including specificity and subgroup analyses.

Rifampin Based Therapy for Patients With Staphylococcus aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-analysis.

BACKGROUND: Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. METHODS: We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). RESULTS: Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. CONCLUSIONS: Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

Mechanically stable rifampin antibiotic cement inhibits Pseudomonas aeruginosa biofilm surface growth.

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. The null hypothesis tests if rifampin use in polymethyl methacrylate (PMMA) cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0, 30, 50, 100, 150, or 200 mg of rifampin into a standard 40 g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipopolysaccharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30 and 50 mg, showed no statistically different mechanical characteristics from control PMMA (p > 0.05). The 100-mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to the control at 12 and 24 h. The ability of PMMA with 100 mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 h makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100 mg of rifampin shows promise in the treatment and prevention of periprosthetic joint infection for total knee and total hip arthroplasty.

Human gelatin thrombin matrix with rifampin for the treatment of prosthetic vascular graft infections.

We aim to describe and report on a novel graft preservation technique using a human gelatin thrombin matrix with rifampin for the treatment of vascular graft infections. Eight patients with vascular graft infections were included, one with bilateral infections, for a total of nine cases from January 2016 through June 2021. All the patients underwent wound exploration and placement of human gelatin thrombin matrix with rifampin. No deaths or allergic reactions had been reported at the 30-day follow-up, with only one major amputation. The graft and limb salvage rates were 77.8% at the 1-year follow-up. The mean time to a major amputation was 122 days, and the mean time to graft excision was 30 days.

Partial recovery of tuberculosis preventive treatment in Brazil after pandemic drawback / Recuperação parcial do tratamento preventivo da tuberculose no Brasil após o recuo pandêmico / Recuperación parcial del tratamiento preventivo de la tuberculosis en Brasil tras el retroceso pandémico

Abstract: Brazil was heavily affected by COVID-19 both with death toll and economically, with absence of a centralized Federal Government response. Tuberculosis (TB) notifications decreased in 2020 but partial recovery was observed in 2021. We have previously shown a sharp (93%) reduction in TB preventive treatment notifications among five Brazilian cities with more than 1,000 notifications in 2021. We hypothesized TB preventive treatment would also recover. We updated the previous analysis by adding other cities that hold more than a 1,000 notifications until 2022. Data aggregated by 2-week periods were extracted from the Information System for Notifying People Undergoing Treatment for LTBI (IL-TB). Biweekly percentage change (BPC) of notifications until October 2022 and outcomes until July 2022 (in the two weeks of TB preventive treatment initiation) were analyzed using Joinpoint software. A total of 39,701 notifications in 11 cities were included, 66% from São Paulo and Rio de Janeiro, Brazil. We found a significant increase of TB preventive treatment notifications in the beginning of 2021 (BPC range 1.4-49.6), with sustained progression in seven out of the 11 cities. Overall, median completion rates were 65%. In most cities, a gradual and steady decrease of treatment completion rates was found, except for Rio de Janeiro and Manaus (Amazonas State, Brazil), where a BPC of 1.5 and 1.2, respectively, was followed by a sustained increase. Notifications and completion proportions of TB preventive treatment were heterogeneous, which partly reflects the heterogeneity in local response to the pandemic. We found that notifications were recovered, and that the sharp 2021 decrease was no longer observed, which suggests delays in notification. In conclusion, the sharp reductions in TB preventive treatment completion rates in most cities might have been caused by delays in reporting; however, the sustained and progressive decrease are a concern.

Resumo: O Brasil foi fortemente atingido pela COVID-19 tanto com número de mortes quanto economicamente, com ausência de uma resposta centralizada do Governo Federal. As notificações de tuberculose (TB) diminuíram em 2020, mas se recuperaram parcialmente em 2021. Já mostramos uma redução acentuada (93%) nas notificações de tratamento preventivo de TB nas cinco cidades brasileiras com mais de 1.000 notificações em 2021. Hipotetizamos que o tratamento preventivo de TB também recuperar-se-ia. Atualizamos a análise anterior acrescentando outras cidades que apresentaram mais de 1.000 notificações até 2022. Os dados agregados por períodos de duas semanas foram extraídos do Sistema de Informação para Notificação das Pessoas em Tratamento de ILTB (IL-TB). As notificações quinzenais de variação percentual até outubro de 2022 e os desfechos até julho de 2022 (nas duas semanas de início do tratamento precoce de TB) foram analisados usando o software Joinpoint. Foram incluídas 39.701 notificações em 11 cidades, sendo 66% delas de São Paulo e do Rio de Janeiro (Brasil). Encontramos um aumento significativo das notificações de tratamento preventivo de TB no início de 2021 (faixa de variação quinzenal percentual 1,4-49,6), com progressão sustentada em 7/11 cidades. No geral, as taxas medianas de conclusão foram de 65%. Na maioria dos municípios, houve queda gradual e constante das taxas de conclusão de tratamento, com exceção do Rio de Janeiro e Manaus (Amazonas, Brasil), onde a variação quinzenal percentual de 1,5 e 1,2, respectivamente, foi acompanhada de aumento sustentado. As notificações e proporções de tratamento preventivo de TB completados foram heterogêneas, o que reflete em parte a diversidade na resposta local à pandemia. No geral, as notificações se recuperaram e a queda acentuada de 2021 não é mais observada, o que sugere atrasos na notificação. Em conclusão, a redução das taxas de conclusão do tratamento preventivo da TB na maioria das cidades pode refletir atrasos na notificação, mas a diminuição sustentada e progressiva das notificações preocupa.

Resumen: Brasil fue seriamente afectado por el COVID-19, tanto con el número de muertes como económicamente, con la ausencia de una respuesta centralizada del Gobierno Federal. Las notificaciones de la tuberculosis (TB) redujeron en 2020, pero aumentaron parcialmente en 2021. Ya mostramos una reducción drástica (el 93%) en las notificaciones del tratamiento preventivo de la TB en las cinco ciudades brasileñas con más de 1.000 notificaciones en 2021. Nuestra hipótesis es que el tratamiento preventivo de la TB también aumentaría. Actualizamos el análisis anterior añadiendo otras ciudades que presentaron más de 1.000 notificaciones hasta 2022. Los datos agregados durante períodos de dos semanas se extrajeron del Sistema de Información de Notificaciones para Personas en Tratamiento por ILTB (IL-TB). Las notificaciones quincenales de cambio porcentual hasta octubre de 2022 y os resultados hasta julio de 2022 (en las dos semanas iniciales del tratamiento precoz de la tuberculosis) se analizaron a través del software Joinpoint. Se incluyeron 39.701 notificaciones en 11 ciudades, siendo el 66% de ellas en São Paulo y Rio de Janeiro, Brasil. Encontramos un aumento significativo de las notificaciones del tratamiento preventivo de la TB a principios de 2021 (rango de cambio porcentual quincenal 1,4-49,6), con progresión sostenida en siete de las once ciudades. En general, las tasas medias de finalización fueron del 65%. En la mayoría de los municipios, hubo una reducción gradual y constante de las tasas de finalización de tratamiento, salvo en Rio de Janeiro y Manaus (Amazonas, Brasil), donde el cambio porcentual quincenal de 1,5 y 1,2, respectivamente, estuvo acompañado de un aumento sostenido. Las notificaciones y proporciones de cumplimentación del tratamiento preventivo de la TB fueron heterogéneas, lo que refleja la heterogeneidad en la respuesta local a la pandemia. En general, las notificaciones aumentaron y ya no se observa la fuerte caída de 2021 lo que refleja en parte retrasos en la notificación. En conclusión, la reducción en las tasas de finalización del tratamiento preventivo de la TB en la mayoría de las ciudades puede reflejar retrasos en la notificación, pero la reducción sostenida y progresiva es una preocupación.

Case report of pulmonary brucellosis complicated by pleural effusion.

Brucellosis is a bacterial disease and one of the most widespread zoonoses transmitted by an animal. It can affect any organ system, but pulmonary involvement is an unusual presentation according to the literature. We report the case of a 32 -year-old lady from Saudi Arabia who suffered from persistent fever and was found to have lobar pneumonia complicated by parapneumonic effusion. She started empirical antibiotics, and many investigations were done. In the end, after more detail about the patient's circumstances, the presumptive diagnosis of Brucella was made by high serology titer. She was effectively treated with doxycycline and rifampicin and completely recovered. In conclusion, pulmonary brucellosis is infrequent and challengeable in diagnosis but should be knowledge, especially in endemic areas of brucellosis.

In Vitro and In Vivo Antimicrobial Activities of Vancomycin and Rifampin against Elizabethkingia anophelis.

Elizabethkingia anophelis has emerged as a critical human pathogen, and a number of isolated reports have described the successful treatment of Elizabethkingia infections with vancomycin, a drug that is typically used to target Gram-positive bacteria. This study employed in vitro broth microdilution checkerboard and time-kill assays, as well as in vivo zebrafish animal models to evaluate the individual and combination antimicrobial effects of vancomycin and rifampin against E. anophelis. The minimum inhibitory concentration ranges of vancomycin and rifampin against 167 isolates of E. anophelis were 16-256 mg/L and 0.06-128 mg/L, respectively. The checkerboard assay results revealed a synergistic effect between vancomycin and rifampin in 16.8% (28/167) of the isolates. Time-kill assays were implemented for 66 isolates, and the two-drug combination had a synergistic interaction in 57 (86.4%) isolates. In vivo zebrafish studies revealed that treatment with vancomycin monotherapy, rifampin monotherapy, or vancomycin-rifampin combination therapy yielded a higher survival rate than the control group treatment with 0.9% saline. The results of this study support the use of vancomycin to treat E. anophelis infections.