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BMC Infectious Diseases May 2024Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various...
BACKGROUND
Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.
CASE PRESENTATION
The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.
CONCLUSION
Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.
Topics: Humans; Male; Middle Aged; Cryptococcosis; Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Liver Failure; Acquired Immunodeficiency Syndrome; Hepatitis B, Chronic; Coinfection; Antitubercular Agents; HIV Infections; AIDS-Related Opportunistic Infections
PubMed: 38802753
DOI: 10.1186/s12879-024-09431-9 -
Frontiers in Pharmacology 2024Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in...
The use of antibiotics in the early stage of acute exacerbation of chronic obstructive pulmonary disease in patients without obvious signs of infection: a multicenter, randomized, parallel-controlled study.
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection.
PURPOSE
To clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection.
METHODS
The impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400 mg/day intravenously for 7 days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7 days.
RESULTS
There were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups ( > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups ( > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group ( < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups ( > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84 days) than in the nonantibiotic group (6.75 days) ( < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group ( < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5 years, with a CRP level >12.56 mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor.
CONCLUSION
Patients who are >62.5 years of age, have a CRP concentration >12.56 mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis.
CLINICAL TRIAL REGISTRATION
(https://www.chictr.org.cn), (ChiCTR1800018921).
PubMed: 38799157
DOI: 10.3389/fphar.2024.1380939 -
Microorganisms May 2024() poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions....
() poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions. This study investigated the prevalence, serotype distribution, virulence gene profiles, and antimicrobial resistance patterns of in ready-to-eat (RTE) food products from Romania. A total of 8151 samples were analyzed, including various processed dairy, bovine, poultry, pork, and fish products. Bacterial isolation was conducted using the classical standard method, followed by confirmation through biochemical and molecular testing. Among the isolated strains, serotypes 1/2a, 1/2b, and 1/2c were identified, with a prevalence of 75% for serotype 1/2a. Additionally, virulence genes specific to listeriolysin O (A) and regulatory factor A (A) were detected in all isolates. Antimicrobial susceptibility testing revealed varying resistance patterns among the strains. Trimethoprim-sulfamethoxazole and oxacillin showed the highest prevalence of resistance at 26.92% and 23.07%, respectively. However, all strains remained susceptible to ciprofloxacin, levofloxacin, and moxifloxacin. Notably, 23.07% of the isolates exhibited multidrug resistance, with the most common pattern being resistance to oxacillin, penicillin, and tetracycline. Analysis of antimicrobial resistance genes identified tetracycline resistance genes, particularly (C), (M), and (K), in a significant proportion of isolates. The presence of C and D genes was also notable, indicating potential mechanisms of resistance. These results emphasize the necessity for ongoing surveillance of in RTE foods and emphasize the importance of thorough monitoring of antimicrobial resistance to guide public health strategies within the European Union.
PubMed: 38792784
DOI: 10.3390/microorganisms12050954 -
IDCases 2024Bedaquiline (BDQ) is an effective drug currently used for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB)...
BACKGROUND
Bedaquiline (BDQ) is an effective drug currently used for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB) treatment. However, resistance to this new drug is emerging. We discussed the characteristics of the first patient in Ethiopia who acquired BDQ and fluoroquinolones (FQs) resistance during treatment follow-up.
CASE REPORT
In this case report, we present the case of a 28-year-old male pulmonary TB patient diagnosed with MDR-TB who is a resident of the Oromia Region of North Shewa, Mulona Sululta Woreda, Ethiopia. Sputum specimen was collected initially and for treatment monitoring using culture and for phenotypic drug susceptibility testing (DST) to first-line and second-line TB drugs. Initially, the patient was infected with a mycobacterial strain resistant to the first-line anti-TB drugs Rifampicin (RIF), Isoniazid (INH), and Pyrazinamide (PZA). Later, during treatment, he acquired additional drug resistance to ethambutol (EMB), ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX), and BDQ. The patient was tested with MTBDR and MTBDR to confirm the presence of resistance-conferring mutation and mutation was detected in and genes. Finally, the patient was registered as having extensively drug-resistant tuberculosis (XDR-TB) and immediately started an individualized treatment regimen.
CONCLUSION
This case report data has revealed the evolution of BDQ resistance during treatment with a BDQ-containing regimen in Ethiopia. Therefore, there is a need for DST to new second-line drugs to monitor and prevent the spread of DR-TB.
PubMed: 38779144
DOI: 10.1016/j.idcr.2024.e01988 -
Photodiagnosis and Photodynamic Therapy May 2024Accurate diagnosis of patients with ulcerative colitis (UC) can reduce their risk of developing colorectal cancer. This study intended to explore whether moxifloxacin,...
BACKGROUND
Accurate diagnosis of patients with ulcerative colitis (UC) can reduce their risk of developing colorectal cancer. This study intended to explore whether moxifloxacin, an agent with fluorescence potential, could promote two-photon microscopy (TPM) diagnosis for mice with dextran sodium sulfate (DSS)-induced colitis, which could imitate human UC.
METHODS
32 Balb/c mice were randomly divided into 4 groups: control, acute colitis, remission colitis and chronic colitis. Fluorescence parameters, imaging performance, and tissue features of different mouse models were compared under moxifloxacin-assisted TPM and label-free TPM.
RESULTS
Excitation wavelength of 720 nm and moxifloxacin labeling time of 2 min was optimal for moxifloxacin-assisted TPM. With moxifloxacin labeling for colonic tissues, excitation power was decreased to 1/10 of that without labeling while fluorescence intensity was increased to 10-fold of that without labeling. Photobleaching was negligible after moxifloxacin labeling and moxifloxacin fluorescence kept stable within 2 hours. Compared with the control group, moxifloxacin fluorescence was reduced in the three colitis groups (P<0.05). Meanwhile, the proportion of enhanced moxifloxacin fluorescence regions was (22.4±1.6)%, (7.7±1.0)%, (13.5±1.7)% and (5.0±1.3)% in the control, acute, remission and chronic groups respectively, with significant reduction in the three colitis groups (P<0.05). Besides, variant tissue features of experimental colitis models were presented under moxifloxacin-assisted TPM, such as crypt opening, glandular structure, adjacent glandular space and moxifloxacin distribution.
CONCLUSIONS
With unique biological interaction between moxifloxacin and colonic mucosa, moxifloxacin-assisted TPM imaging is feasible and effective for accurate diagnosis of different stages of experimental colitis.
PubMed: 38777309
DOI: 10.1016/j.pdpdt.2024.104220 -
The Lancet. Infectious Diseases May 2024The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to...
Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial.
BACKGROUND
The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ. We compared 4 months of BPaMZ to the standard 6 months of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) in DS-TB. 6 months of BPaMZ was assessed in DR-TB.
METHODS
SimpliciTB was a partially randomised, phase 2c, open-label, clinical trial, recruiting participants at 26 sites in eight countries. Participants aged 18 years or older with pulmonary TB who were sputum smear positive for acid-fast bacilli were eligible for enrolment. Participants with DS-TB had Mycobacterium tuberculosis with sensitivity to rifampicin and isoniazid. Participants with DR-TB had M tuberculosis with resistance to rifampicin, isoniazid, or both. Participants with DS-TB were randomly allocated in a 1:1 ratio, stratified by HIV status and cavitation on chest radiograph, using balanced block randomisation with a fixed block size of four. The primary efficacy endpoint was time to sputum culture-negative status by 8 weeks; the key secondary endpoint was unfavourable outcome at week 52. A non-inferiority margin of 12% was chosen for the key secondary outcome. Safety and tolerability outcomes are presented as descriptive analyses. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov (NCT03338621) and is completed.
FINDINGS
Between July 30, 2018, and March 2, 2020, 455 participants were enrolled and received at least one dose of study treatment. 324 (71%) participants were male and 131 (29%) participants were female. 303 participants with DS-TB were randomly assigned to 4 months of BPaMZ (n=150) or HRZE (n=153). In a modified intention-to-treat (mITT) analysis, by week 8, 122 (84%) of 145 and 70 (47%) of 148 participants were culture-negative on 4 months of BPaMZ and HRZE, respectively, with a hazard ratio for earlier negative status of 2·93 (95% CI 2·17-3·96; p<0·0001). Median time to negative culture (TTN) was 6 weeks (IQR 4-8) on 4 months of BPaMZ and 11 weeks (6-12) on HRZE. 86% of participants with DR-TB receiving 6 months of BPaMZ (n=152) reached culture-negative status by week 8, with a median TTN of 5 weeks (IQR 3-7). At week 52, 120 (83%) of 144, 134 (93%) of 144, and 111 (83%) of 133 on 4 months of BPaMZ, HRZE, and 6 months of BPaMZ had favourable outcomes, respectively. Despite bacteriological efficacy, 4 months of BPaMZ did not meet the non-inferiority margin for the key secondary endpoint in the pre-defined mITT population due to higher withdrawal rates for adverse hepatic events. Non-inferiority was demonstrated in the per-protocol population confirming the effect of withdrawals with 4 months of BPaMZ. At least one liver-related treatment-emergent adverse effect (TEAE) occurred among 45 (30%) participants on 4 months of BPaMZ, 38 (25%) on HRZE, and 33 (22%) on 6 months of BPaMZ. Serious liver-related TEAEs were reported by 20 participants overall; 11 (7%) among those on 4 months of BPaMZ, one (1%) on HRZE, and eight (5%) on 6 months of BPaMZ. The most common reasons for discontinuation of trial treatment were hepatotoxicity (ten participants [2%]), increased hepatic enzymes (nine participants [2%]), QTcF prolongation (three participants [1%]), and hypersensitivity (two participants [<1%]).
INTERPRETATION
For DS-TB, BPaMZ successfully met the primary efficacy endpoint of sputum culture conversion. The regimen did not meet the key secondary efficacy endpoint due to adverse events resulting in treatment withdrawal. Our study demonstrated the potential for treatment-shortening efficacy of the BPaMZ regimen for DS-TB and DR-TB, providing clinical validation of a murine model widely used to identify such regimens. It also highlights that novel, treatment-shortening TB treatment regimens require an acceptable toxicity and tolerability profile with minimal monitoring in low-resource and high-burden settings. The increased risk of unpredictable severe hepatic adverse events with 4 months of BPaMZ would be a considerable obstacle to implementation of this regimen in settings with high burdens of TB with limited infrastructure for close surveillance of liver biochemistry. Future research should focus on improving the preclinical and early clinical detection and mitigation of safety issues together and further efforts to optimise shorter treatments.
FUNDING
TB Alliance.
PubMed: 38768617
DOI: 10.1016/S1473-3099(24)00223-8 -
Indian Journal of Ophthalmology May 2024To assess the safety and efficacy of transzonular moxifloxacin and dexamethasone versus standard postoperative topical drug regimen in phacoemulsification.
PURPOSE
To assess the safety and efficacy of transzonular moxifloxacin and dexamethasone versus standard postoperative topical drug regimen in phacoemulsification.
DESIGN
Nonrandomized prospective study.
METHODS
The study included 100 eyes of 100 age and gender-matched individuals with senile cataract undergoing routine phacoemulsification. The patients were consecutively divided into transzonular (TZ = 50) and topical (TP = 50) groups. Both the groups were followed up for 4 weeks and assessed for intraocular inflammation, visual acuity, changes in intraocular pressure (IOP), and any adverse events.
RESULTS
The grades of inflammation were significantly lower in TZ as compared to the TP group ( P < 0.001). The IOP remained normal and comparable in both the groups. Most of the patients in the two groups attained a visual acuity of 0.2 or better at the end of the follow-up. No adverse effects and increased rate of endophthalmitis were noted in TZ group.
CONCLUSION
A one-time peroperative TZ moxifloxacin and dexamethasone combination is a safe and effective method to control postoperative inflammation after cataract surgery. A word of caution though, due precautions to be exercised to prevent the risk of inflammation and endophthalmitis.
PubMed: 38767558
DOI: 10.4103/IJO.IJO_2697_23 -
International Journal of Ophthalmology 2024To investigate the effectiveness of combination therapy with transzonular triamcinolone-moxifloxacin and conventional perioperative drops in reducing postoperative...
AIM
To investigate the effectiveness of combination therapy with transzonular triamcinolone-moxifloxacin and conventional perioperative drops in reducing postoperative complications of cataract surgery.
METHODS
Electronic medical records of cataract surgery patients (single surgeon) were reviewed from January 2018 to September 2021. The rate of postoperative complications including prolonged and/or recurrent postoperative inflammation, endophthalmitis, cystoid macular edema (CME), and intraocular pressure (IOP) was compared between the patients receiving combinative therapy and patients receiving drops only.
RESULTS
Totally 596 patients and 1057 eyes (Combinative-Therapy group 493 and Drop-Only group 564) were included in this study. Using combination therapy reduced the relative risk of postoperative inflammation by 26.9% (16.6% Combinative-Therapy 22.7% Drop-Only, =0.013). The incidence of endophthalmitis was 0 in Combinative-Therapy group 0.5% in Drop-Only group (relative risk reduction 100%), although not statistically significant (=0.10). The incidence of severe IOP spikes was not significantly different between Combinative-Therapy (2.4%) and Drop-Only (1.6%) groups (=0.33). The relative risk of postoperative CME was 51.4% less in three months follow up visit in Combinative-Therapy group, although not statistically significant (=0.07). The visual outcome 1-month postop. (best corrected visual acuity) was significantly better in Combinative-Therapy (logMAR 0.10) compared to Drop-Only (logMAR 0.14) groups (=0.02) while the baseline visual acuity was not significantly different.
CONCLUSION
The combinative approach of transzonular triamcinolone-moxifloxacin plus perioperative eyedrops is an effective method to minimize postoperative inflammation, with better visual outcomes. It could potentially reduce the risk of postoperative endophthalmitis and CME (near-significant -values; larger studies could analyze better considering low incidence).
PubMed: 38766326
DOI: 10.18240/ijo.2024.05.08 -
BMC Genomics May 2024Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment....
BACKGROUND
Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium.
METHODS
In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool.
RESULTS
We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins.
CONCLUSION
This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.
Topics: Mycobacterium tuberculosis; Polymorphism, Single Nucleotide; Whole Genome Sequencing; Genome, Bacterial; Humans; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Mutation; Antitubercular Agents; Bacterial Proteins
PubMed: 38745294
DOI: 10.1186/s12864-024-10390-3 -
Journal of Infection in Developing... Apr 2024Mycobacterium marinum infection rarely occurs and has atypical symptoms. It is challenging to distinguish disseminated M. marinum infection from multifocal dermatosis...
INTRODUCTION
Mycobacterium marinum infection rarely occurs and has atypical symptoms. It is challenging to distinguish disseminated M. marinum infection from multifocal dermatosis caused by other factors clinically.
CASE PRESENTATION
Herein, we reported a 68-year-old male patient with Human Immunodeficiency Virus (HIV) who presented redness and swelling in his left hand after being stabbed by marine fish for over 2 months. Mycobacterium tuberculosis infection was considered according to biochemical and pathological examinations, while empirical anti-infection treatment was ineffective.
RESULTS
The metagenomic next-generation sequencing (mNGS) detected a large amount of M. marinum sequences, and the patient was finally diagnosed with M. marinum infection. After one month of combination therapy with ethambutol, rifabutin, moxifloxacin, and linezolid, the swelling disappeared significantly. In this case, the successful application of mNGS in diagnosing and treating M. marinum infection has improved the understanding of the microbe both in the laboratory and clinically, especially in patients with HIV.
CONCLUSIONS
For diseases with atypical symptoms or difficulty in determining the pathogens, mNGS is suggested in clinical procedures for rapid and accurate diagnosis and treatment.
Topics: Humans; Male; Mycobacterium Infections, Nontuberculous; Aged; Mycobacterium marinum; HIV Infections; High-Throughput Nucleotide Sequencing; Metagenomics; Ethambutol; Anti-Bacterial Agents
PubMed: 38728638
DOI: 10.3855/jidc.18114