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Scientific Reports Feb 2024Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori...
Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Retrospective Studies; Gastritis, Atrophic; Amoxicillin; Clarithromycin; Stomach Diseases; Levofloxacin; Proton Pump Inhibitors; Furazolidone; Drug Resistance, Bacterial; Metronidazole
PubMed: 38418852
DOI: 10.1038/s41598-024-55589-2 -
Diagnostic Microbiology and Infectious... Jul 2023Gepotidacin is a novel agent in development for treatment of gonorrhea and uncomplicated urinary tract infection. This study determined the effect of urine on the in...
Analysis of the effect of urine on the in vitro activity of gepotidacin and levofloxacin against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus.
Gepotidacin is a novel agent in development for treatment of gonorrhea and uncomplicated urinary tract infection. This study determined the effect of urine on the in vitro activity of gepotidacin and levofloxacin against relevant bacteria. Study strains were tested by Clinical and Laboratory Standards Institute broth microdilution and with method variations: CAMHB with 25%, 50%, 100% urine and pH adjusted 100% urine. Mean dilution difference (DD) of urine minimum inhibitory concentration (MICs) were <1 dilution of CAMHB MICs with some exceptions: Gepotidacin mean DD: Escherichia coli and Staphylococcus saprophyticus 100% urine (1.5 and 1.2, respectively) and S. saprophyticus pH 7.3 and 8.1 adjusted 100% urine (1.5 and 1.4, respectively); Levofloxacin mean DD: S. saprophyticus pH 7.3 adjusted 100% urine (1.5) and all species pH 8.1 adjusted 100% urine (1.2-1.8). Effects of urine on gepotidacin and levofloxacin MICs was minimal and not inclusive of all strains. Further analysis is warranted to fully assess the impact of urine on gepotidacin activity.
Topics: Humans; Levofloxacin; Anti-Bacterial Agents; Staphylococcus saprophyticus; Staphylococcus epidermidis; Escherichia coli; Microbial Sensitivity Tests
PubMed: 37201401
DOI: 10.1016/j.diagmicrobio.2023.115946 -
Infection and Drug Resistance 2023, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. infection is associated with high mortality rates....
The Activities of Antimicrobials Against Isolates and Evaluation of Clinical Outcomes Among Treatment Regimens in Patients with Infections: A Retrospective Multicenter Cohort Study.
PURPOSE
, a multidrug-resistant pathogen can cause hospital-acquired infections such as pneumonia, or bloodstream infection. infection is associated with high mortality rates. This retrospective study examined the antimicrobial susceptibility profile of clinical isolates and evaluated clinical outcomes, treatment regimens, and risk factors associated with 30-day mortality or treatment failure of infections at three tertiary care hospitals in Central Thailand.
PATIENTS AND METHODS
The characteristics, microbiological data, and clinical treatment outcomes were derived from medical records obtained from three tertiary care hospitals in Central Thailand from January 2017 to October 2022. The primary outcomes were treatment failure and 30-day mortality. The antimicrobial susceptibility rates of trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and ceftazidime were determined by minimum inhibitory concentration (MIC), which were based on broth microdilution and clear zone diameters using the disk diffusion method. However, we also report the susceptibility of minocycline and tigecycline in some clinical strains (n = 149) and determined by MIC with E-test method.
RESULTS
The antimicrobial susceptibility rates to TMP-SMX, levofloxacin, and ceftazidime were 97.1%, 93%, and 55.3%, respectively. The treatment failure rate and 30-day mortality were 66.3% and 49%, respectively. Significant factors associated with treatment failure included APACHE II score ≥15 (OR 3.37, 95% confidence interval (CI) 1.46-7.76), polymicrobial infections (OR 3.20, 95% CI 1.35-7.55). The significant factors associated with reduced treatment failure was treatment with TMP-SMX-based regimen (OR 0.29, 95% CI 0.11-0.76). The 30-day mortality rate was associated with APACHE II score ≥15 (OR 3.27, 95% CI 1.45-7.39) and septic shock (OR 2.53, 95% CI 1.36-4.69).
CONCLUSION
The results indicate a high mortality rate for infection. The predictive factors for an unfavourable outcome were severity of illness, septic shock, and non-use of TMP-SMX. Therefore, a TMP-SMX-based regimen is recommended for the treatment of infections.
PubMed: 37581163
DOI: 10.2147/IDR.S416678 -
Clinical Infectious Diseases : An... Mar 2024Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children.
METHODS
Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses.
RESULTS
Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax.
CONCLUSIONS
Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.
Topics: Child; Adult; Infant, Newborn; Humans; Infant; Levofloxacin; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Rifampin; Tablets
PubMed: 38340060
DOI: 10.1093/cid/ciae024 -
BMC Microbiology Jul 2023Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of...
Molecular characterization of multidrug-resistant non-typeable Haemophilus influenzae with high-level resistance to cefuroxime, levofloxacin, and trimethoprim-sulfamethoxazole.
BACKGROUND
Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance.
RESULTS
Thirteen (50%) MDR NTHi isolates were obtained; of these, 92.3% were non-susceptible to ampicillin, 30.8% to amoxicillin-clavulanate, 61.5% to cefuroxime, 61.5% to ciprofloxacin/levofloxacin, 92.3% to trimethoprim-sulfamethoxazole, 30.8% to tetracycline, and 7.7% to azithromycin. Eight ampicillin-resistant isolates were β-lactamase positive; of these, 6 carried bla and 2 carried bla, whereas 4 were β-lactamase negative. Genetic variations in mrdA, mepA, and pbpG were correlated with amoxicillin-clavulanate non-susceptibility, whereas variations in ftsI and lpoA conferred cefuroxime resistance. Five variations in gyrA, 2 in gyrB, 3 in parC, 1 in parE, and 1 in the parC-parE intergenic region were associated with levofloxacin/ciprofloxacin non-susceptibility. Among these genes, 8 variations were linked to high-level levofloxacin resistance. Six variations in folA were associated with trimethoprim-sulfamethoxazole resistance. Plasmid-bearing tet(B) and mef(A) genes were responsible for tetracycline and azithromycin resistance in 4 and 1 MDR isolates, respectively.
CONCLUSIONS
This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.
Topics: Humans; Haemophilus influenzae; Cefuroxime; Levofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Azithromycin; Microbial Sensitivity Tests; Anti-Bacterial Agents; Ampicillin; Haemophilus Infections; Amoxicillin-Potassium Clavulanate Combination; Tetracycline; Ciprofloxacin; beta-Lactamases
PubMed: 37407940
DOI: 10.1186/s12866-023-02926-6 -
AAPS PharmSciTech Nov 2023Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their...
Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their green properties, deep eutectic systems have been heralded as having the potential to be at the forefront of pharmaceutical applications. In this work, capric acid and geranic acid, two examples of medium-chain saturated and polyunsaturated fatty acids, were employed to enhance the pharmaceutical properties and the antibacterial activity of levofloxacin. To this end, levofloxacin formulations with either capric or geranic acid were prepared and characterized using appropriate techniques. Levofloxacin was utilized to create innovative deep eutectic systems in conjunction with capric acid at three different molar ratios: 1:9, 2:8 and 3:7. This was confirmed through a rigorous analysis involving nuclear magnetic resonance, infrared spectroscopy and differential scanning calorimetry. Furthermore, it is noteworthy that geranic acid demonstrated an impressive threefold improvement in levofloxacin's solubility compared to its solubility in aqueous solutions. The antibacterial activity of the novel combinations of levofloxacin with either fatty acid was evaluated using a checkerboard titration assay. Gratifyingly, both formulations exhibited synergistic effects against a panel of levofloxacin-sensitive and resistant Gram-negative bacteria. In conclusion, the observed superior antibacterial activity of levofloxacin illuminates the potential use of fatty acid-based formulations and deep eutectic systems as green and innovative strategies to combat the global antimicrobial resistance problem.
Topics: Levofloxacin; Fatty Acids; Anti-Bacterial Agents; Decanoic Acids; Fatty Acids, Unsaturated; Pharmaceutical Preparations; Solvents
PubMed: 38030950
DOI: 10.1208/s12249-023-02701-w -
Microorganisms Jul 2023Dental caries is a biofilm-mediated, sugar-driven, multifactorial, dynamic disease that results in the phasic demineralization and remineralization of dental hard...
Dental caries is a biofilm-mediated, sugar-driven, multifactorial, dynamic disease that results in the phasic demineralization and remineralization of dental hard tissues. Despite scientific advances in cariology, dental caries remains a severe global concern. The aim of this study was to determine the optimization of microbial and molecular techniques for the detection of cariogenic pathogens in dental caries patients, the prevalence of cariogenic bacteria on the basis of socioeconomic, climatological, and hygienic factors, and in vitro evaluation of the antimicrobial activity of selected synthetic antibiotics and herbal extracts. In this study, oral samples were collected from 900 patients for bacterial strain screening on a biochemical and molecular basis. Plant extracts, such as ginger, garlic, neem, tulsi, amla, and aloe vera, were used to check the antimicrobial activity against the isolated strains. Synthetic antimicrobial agents, such as penicillin, amoxicillin, erythromycin, clindamycin, metronidazole, doxycycline, ceftazidime, levofloxacin, and ciprofloxacin, were also used to access the antimicrobial activity. Among 900 patients, 63% were males and 37% were females, patients aged between 36 and 58 (45.7%) years were prone to disease, and the most common symptom was toothache (61%). For oral diseases, 21% used herbs, 36% used antibiotics, and 48% were self-medicated, owing to sweets consumption (60.66%) and fizzy drinks and fast food (51.56%). (29.11%) and (28.11%) were found as the most abundant strains. Seven bacterial strains were successfully screened and predicted to be closely related to genera , , , , , , and . Among plant extracts, the maximum zone of inhibition was recorded by ginger (22.36 mm) and amla (20.01 mm), while among synthetic antibiotics, ciprofloxacin and levofloxacin were most effective against all microbes. This study concluded that phyto extracts of ginger and amla were considered suitable alternatives to synthetic antibiotics to treat dental diseases.
PubMed: 37630520
DOI: 10.3390/microorganisms11081952 -
Journal of Medical Microbiology Nov 2023is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor...
is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor (PPI) to suppress stomach acid. The World Health Organization designated clarithromycin-resistant as a high priority pathogen for drug development, due to increasing antibiotic resistance globally. There is no routine surveillance of primary antimicrobial sensitivities in the UK, and published data are lacking. This study aimed to characterize antimicrobial sensitivities of isolates collected in Nottingham, UK, between 2001 and 2018. Gastric biopsy samples were collected, with informed written consent and ethics approval, from 162 patients attending the Queen's Medical Centre in Nottingham for an upper GI tract endoscopy. Antibiotic sensitivity was assessed using E-Tests and a more cost-effective disc diffusion test. The clarithromycin, amoxicillin and levofloxacin disc diffusion tests provided identical results to E-Tests on a subset of 30 isolates. Disparities were observed in the metronidazole test results, however. In total, 241 isolates from 162 patients were tested using at least one method. Of all isolates, 28 % were resistant to clarithromycin, 62 % to metronidazole and 3 % to amoxicillin, which are used in first-line therapies. For those antibiotics used in second- and third-line therapies, 4 % were resistant to levofloxacin and none of the isolates were resistant to tetracycline. Resistance to more than one antibiotic was found in 27 % of isolates. The frequency of patients with a clarithromycin-resistant strain increased dramatically over time: from 16 % between 2001 and 2005 to 40 % between 2011 and 2018 (=0.011). For the same time periods, there was also an increase in those with a metronidazole-resistant strain (from 58 to 78 %; =0.05). The frequencies of clarithromycin and metronidazole resistance were higher in isolates from patients who had previously received eradication therapy, compared to those who had not (40 % versus 77 %, and 80 % versus 92 %, respectively). Of 79 pairs of isolates from the antrum and corpus regions of the same patient's stomach, only six had differences in their antimicrobial susceptibility profiles. Although there was high and increasing resistance to clarithromycin and metronidazole, there was no resistance to tetracycline and the frequencies of amoxicillin and levofloxacin resistance were very low.
Topics: Humans; Clarithromycin; Metronidazole; Helicobacter pylori; Levofloxacin; Helicobacter Infections; Incidence; Microbial Sensitivity Tests; Anti-Bacterial Agents; Amoxicillin; Tetracycline; Drug Resistance, Microbial; United Kingdom
PubMed: 37962209
DOI: 10.1099/jmm.0.001776 -
Microorganisms Jul 2023The gut microbiota, as a major source of opportunistic pathogens, poses a great threat to systemic infection, whereas the role of the gut microbiota in sepsis is...
The gut microbiota, as a major source of opportunistic pathogens, poses a great threat to systemic infection, whereas the role of the gut microbiota in sepsis is underestimated. Here, we aimed to explore the effects of different gut microbiota patterns (namely, enterotypes) in cecal ligation and puncture (CLP)-induced murine sepsis. To achieve this purpose, we built four kinds of enterotypes by exposing mice to different types of antibiotics (azithromycin, amoxicillin, metronidazole, and levofloxacin). The results showed that antibiotic exposure induced different enterotypes, which, in turn, led to varying levels of systemic inflammation in septic mice, with amoxicillin-associated enterotypes exhibiting the most severe inflammation, followed by metronidazole, azithromycin, and levofloxacin. Specifically, the amoxicillin-associated enterotype was characterized by an abundance of intestinal opportunistic pathogens, including Enterobacteriaceae, Sutterellaceae, and Morganellaceae. This enterotype played a significant role in promoting the pathogenic potential of the gut microbiota, ultimately contributing to the development of severe systemic inflammation. Furthermore, the amoxicillin-associated enterotype exaggerated the sepsis-related liver injury, as evidenced by higher levels of alanine aminotransferase, aspartate transaminase, and hepatic malondialdehyde. The results of the RNA sequencing and the fecal suspension intraperitoneal injection sepsis model indicated that the amoxicillin-associated enterotype provoked acute hepatic immune responses and led to more significant metabolic compensation in the event of sepsis. Collectively, we concluded that the gut microbiota was one crucial factor for heterogeneity in sepsis, where the modulated gut microbiota likely prevented or reduced the serious consequences of sepsis, at least in gut-derived sepsis.
PubMed: 37512913
DOI: 10.3390/microorganisms11071741 -
Infection and Drug Resistance 2023is an opportunistic pathogen involved in number of hospital-acquired infections such as catheter-associated urinary tract infections, bacteremia, septicemia, skin...
BACKGROUND
is an opportunistic pathogen involved in number of hospital-acquired infections such as catheter-associated urinary tract infections, bacteremia, septicemia, skin infections, and ventilator-associated pneumoniae. Biofilm formation is an important trait implicated in chronic infections, such as cystic fibrosis and chronic pulmonary obstruction. We evaluated effects of gentamicin, cefepime, and ciprofloxacin on biofilm of
MATERIALS AND METHODS
A total of 266 isolates were collected from the Armed Forces Institute of Pathology (AFIP). Antibiotic susceptibility was assessed by double disk synergy testing. ESBL and carbapenemase detection was performed by phenotypic testing. Molecular screening of the genes was done by PCR. Micro-dilution broth method was used to determine minimum inhibitory concentrations of antibiotics. Biofilm formation was done by micro-titer plate assay.
RESULTS
Overall, 20% of the isolates were extensively drug-resistant (XDR-PA), and 25% were multi-drug-resistant (MDR-PA). Likewise, 43% of the isolates were ESBL producers, and carbapenemase production was detected in 40% of the isolates. Molecular analysis confirmed occurrence of different resistant factors in ESBL-positive isolates; 67% carried , 62% , 41% , 34% bla, and 33% . In addition, 68% of the carbapenem-resistant isolates were positive for , 25% for , and 22% for . Biofilm formation was assessed for 234 isolates, out of which 28% were strong biofilm formers. Moderate and weak biofilm formers constituted 46% and 23%, respectively. Overall, ciprofloxacin, levofloxacin, and cefepime showed inhibitory effects on biofilms. Antibiotics in combination showed strong synergistic effects (ciprofloxacin and cefepime), while gentamicin and cefepime resulted in complete eradication of biofilm.
CONCLUSION
We confirm strong synergistic effects of gentamicin and cefepime that completely eradicated biofilm. We further confirm inhibitory effects of ciprofloxacin, levofloxacin, and cefepime on biofilms. Hence, combination therapy can be more effective against biofilm-associated infections.
PubMed: 37692466
DOI: 10.2147/IDR.S426111