Acinetobacter baumannii is a major pathogen in hospital-acquired infections notorious for its strong acquired resistance and complex drug resistance mechanisms. Owing to the lack of effective drugs, the mortality rate of extensively drug-resistant A. baumannii pneumonia can reach as high as 65%. This article analyzes a case where a combination of cefoperazone-sulbactam, polymyxin B, and minocycline with rifampicin successfully treated XDR-AB pulmonary infection. Combination therapy is effective and has a particular clinical value.

Although the incidence of infections in orthopedic surgeries, including periprosthetic surgeries, remains low at approximately 1-2%, the number of surgeries and the incidence of drug-resistant bacteria is increasing. The cost and morbidity associated with revision surgeries are huge. More effective drug combinations and delivery methods are urgently needed. In this paper, three anti-infective drugs (vancomycin, rifampicin, and silver sulfadiazine) have been jointly and effectively electrospun in thin (0.1 mm) flexible nanofiber mats of either poly (methyl methacrylate) (PMMA) or poly (lactic-co-glycolic acid) (PLGA). The inclusion of poly (ethylene glycol) (PEG) enabled optimal drug release with a reduced water contact angle for wetting. The controlled release of these three agents from 20% PEG (w/w to polymer)-blended PMMA or PLGA nanofiber mats may allow for the prophylactical prevention of implant-related infections or provide methods to treat orthopedic infections at the time of revision surgeries. These combinations of drugs provide excellent additive or synergistic antibiotic action against a broader spectrum of bacteria than each drug alone.

Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB control and treatment. Stratified data on MDR-TB, particularly in the high-burden western Kenya region, remain unknown. This data is important to monitor the efficacy of TB control and treatment efforts. Herein, we determined the molecular epidemiology of drug-resistant TB and associated risk factors in western Kenya. This was a non-experimental, population-based, cross-sectional study conducted between January and August 2018. Morning sputum samples of individuals suspected of pulmonary TB were collected, processed, and screened for Mycobacterium tuberculosis (Mtb) and drug resistance using line probe assay (LPA) and Mycobacterium growth indicator tubes (MGIT) culture. MGIT-positive samples were cultured on brain heart infusion (BHII) agar media, and the presence of Mtb was validated using Immunochromatographic assay (ICA). Drug sensitivity was performed on MGIT and ICA-positive but BHI-negative samples. Statistical significance was set at P < 0.05. Of the 622 Mtb isolates, 536 (86.2%) were susceptible to RIF and INH. The rest, 86 (13.83%), were resistant to either drugs or both. A two-sample proportional equality test revealed that the MDR-TB prevalence in western Kenya (5%) did not vary significantly from the global MDR-TB estimate (3.9%) (P = 0.196). Men comprised the majority of susceptible and resistant TB (75.9% and 77.4%%, respectively). Also, compared with healthy individuals, the prevalence of HIV was significantly higher in MDR-TB patients (35.9% vs 5.6%). Finally, TB prevalence was highest in individuals aged 25-44 years, who accounted for 58.4% of the total TB cases. Evidently, the prevalence of MDRTB in western Kenya is high. Particular attention should be paid to men, young adults, and those with HIV, who bear the greatest burden of resistant TB. Overall, there is a need to refine TB control and treatment programs in the region to yield better outcomes.

Staphylococcus aureus is a major causative pathogen of osteomyelitis. Intracellular infections of resident bone cells including osteocytes can persist despite gold-standard clinical intervention. The mechanisms by which intracellular S. aureus evades antibiotic therapy are unknown. In this study, we utilised an in vitro S. aureus infection model of human osteocytes to investigate whether antibiotic-mediated dysregulation of autophagy contributes to this phenomenon. Infected or non-infected osteocyte-like cells were exposed to combinations of rifampicin, vancomycin, and modulators of autophagy. Intracellular bacterial growth characteristics were assessed using colony-forming unit (CFU) analysis, viable bacterial DNA abundance, and the rate of escape into antibiotic-free medium, together with measures of autophagic flux. Rifampicin, alone or in combination with vancomycin, caused a rapid decrease in the culturability of intracellular bacteria, concomitant with stable or increased absolute bacterial DNA levels. Both antibiotics significantly inhibited autophagic flux. However, modulation of autophagic flux did not affect viable bacterial DNA levels. In summary, autophagy was shown to be a factor in the host-pathogen relationship in this model, as its modulation affected the growth state of intracellular S. aureus with respect to both their culturability and propensity to escape the intracellular niche. While rifampicin and vancomycin treatments moderately suppressed autophagic flux acutely, this did not explain the paradoxical response of antibiotic treatment in decreasing S. aureus culturability whilst failing to clear bacterial DNA and hence intracellular bacterial load. Thus, off-target effects of rifampicin and vancomycin on autophagic flux in osteocyte-like cells could not explain the persistent S. aureus infection in these cells.

Folliculitis decalvans (FD) is a rare type of inflammatory scalp disorder that leads to scarring alopecia. It is classified as primary neutrophilic cicatricial alopecia. FD presents a challenging scenario in clinical dermatology due to its rarity, resistance to treatment, and potential for scarring alopecia. This inflammatory scalp disorder primarily affects middle-aged adults, predominantly males. While its exact pathogenesis remains uncertain, a deficient host immune response to Staphylococcus aureus infection is hypothesized. Therapeutic interventions for FD pose difficulties, with limited treatment options available A 58-year-old female patient presented with a history of follicular papules that gradually progressed to form clusters of pustules, crusting, and hemorrhagic lesions with tufting of hairs on the crown area of the scalp, and was diagnosed with FD. Considering isotretinoin\'s role in inhibiting abnormal keratinization and inflammation, and rifampicin\'s ability to eradicate S. aureus, the combination of both provides a comprehensive approach to tackling the underlying factors contributing to FD. Despite previous unsuccessful treatments, combination therapy with isotretinoin and rifampicin yielded a remarkable outcome, prompting further exploration of this approach.

Persister cells are transiently tolerant to antibiotics and are associated with recalcitrant chronic infections due to recolonization of host cells after antibiotic removal. Brucella spp. are facultative pathogens that establish intracellular infection cycles in host cells which results in chronic persistent infections. Brucella abortus forms multi-drug persister cells which are promoted by the (p)ppGpp synthetase Rsh during rifampicin exposure. Here, we confirmed that Rsh promoted persister cells formation in B. abortus stationary phase treated with rifampicin and enrofloxacin. Deletion of the gene for Rsh decreased persister cells level in the presence of these drugs in different growth phases. However, persister cells formation by deletion strain varied in different growth phases in the presence of other antibiotics. Rsh also was involved in persister cells formation during rifampicin treatment under certain stress conditions, including acidic conditions, exposure to PBS, and heat stress. Moreover, Rsh impacted persister cell levels during rifampicin or enrofloxacin treatment in RAW264.7 macrophages. Certain typeIItoxin-antitoxin modules were upregulated under various stress conditions in B. abortus. We established that Rsh positively regulated the type II toxin-antitoxin mbcTA. Moreover, rifampicin-tolerant persister cells formation was elevated and ATP levels were decreased when mbcTA promoter was overexpressed in Rsh deletion background in stationary phase. Our results establish that (p)ppGpp synthetase Rsh plays a key role in B. abortus persistence and may serve as a potent novel target in combination with rifampicin in the development of new therapeutic approaches and prevention strategies to treat chronic infections of Brucella.

Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.

Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to brucellosis treatment, enhancing the efficacy of doxycycline and rifampicin through the use of poly (lactic-co-glycolic) acid coupled with cadmium-telluride quantum dots (Dox-Rif-PLGA@CdTe). The double emulsion solvent evaporation method was employed to prepare Dox-Rif-PLGA@CdTe. The study scrutinized the physicochemical attributes of these nanoparticles. The impact of antibiotic-loaded nanoparticles on Brucella melitensis was evaluated through well diffusion, minimum inhibitory concentration (MIC), and cell culture. The chemical analysis results demonstrated a possibility of chemical reactions occurring among the constituents of nanoparticles. Assessments using the well diffusion and MIC methods indicated that the impact of free drugs and nanoparticles on bacteria was equivalent. However, the drug-loaded nanoparticles significantly decreased the colony-forming units (CFUs) within the cell lines compared to free drugs. In conclusion, the synthesis of nanoparticles adhered to environmentally friendly practices and demonstrated safety. The sustained drug release over 100 h facilitated drug accumulation at the bacterial site, resulting in a heightened therapeutic effect on B. melitensis and improved outcomes in brucellosis treatment. The application of these synthesized nanodrugs exhibited promising therapeutic potential.

This case report presents an unusual occurrence of miliary tuberculosis with thyroid tuberculosis in a 75-year-old male patient, who successfully completed the treatment with rifabutin after rifampicin-induced thrombocytopenia. The patient has been suffering from diabetes mellitus and chronic heart failure, and had coronavirus disease of 2019 (COVID-19) just before being diagnosed with miliary tuberculosis. The patient had not been prescribed immunosuppressants and steroids. Chest computed tomography (CT) scans revealed multiple tiny nodules diffusely and equally distributed in bilateral lung fields. Subsequently, polymerase chain reaction (PCR) techniques on the urine samples and culture of sputum demonstrated positivity for Mycobacterium tuberculosis. Thus, we conclusively identified miliary tuberculosis and initiated treatment using anti-tuberculosis drugs. During treatment, the patient developed thyroid tuberculosis, resulting in an enlarged thyroid and hoarseness, but these symptoms improved with continued use of the anti-tuberculosis drugs. Moreover, regarding treatment, the rifabutin dosage was completed after changing drugs due to rifampicin-induced thrombocytopenia. Notably, miliary tuberculosis is rarely complicated by thyroid tuberculosis as a paradoxical reaction, and the substitution of rifabutin for rifampicin-induced thrombocytopenia is not fully studied. We present this case alongside relevant prior data for comprehensive clinical insight.

The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.