Clostridioides difficile infection (CDI) remains a major healthcare challenge due to recurrent disease, spore persistence, and biofilm-associated tolerance, while conventional antibiotics often disrupt gut microbiota. Here, we report a star-shaped poly(l-lysine) dendrimer (G3-PLL9) formulated into hyaluronic acid-based microgels for targeted oral delivery to the inflamed colon. G3-PLL9 exhibited potent antimicrobial activity, including rapid bactericidal effects, superior spore inhibition compared with vancomycin, and robust biofilm disruption at subinhibitory concentrations. In a murine CDI model, rectal administration of G3-PLL9 alleviated clinical symptoms, reduced tissue damage, and lowered recurrence risk. To enable oral therapy, G3-PLL9 was incorporated into hyaluronic acid microgels, achieving site-specific release through hyaluronidase-mediated degradation in the inflamed colon. Importantly, treatment preserved commensal gut microbiota more effectively than vancomycin. Collectively, these findings highlight G3-PLL9 microgels as a microbiota-sparing therapeutic that targets multiple stages of CDI pathogenesis─including spores and biofilms─and demonstrate their potential for clinical translation.

OBJECTIVES:To evaluate the prognostic role of initial band percentages in adults presenting to the emergency department (ED) with bacteremia. METHODS:This 8-year retrospective cohort study included treatment-naïve adults with bacteremia who underwent a manual differential hemogram. The primary outcome was 30-day mortality after ED arrival. The association between initial band percentages and mortality was analyzed using a logistic regression model adjusted for independent prognostic factors. RESULTS:Of the total 5558 patients, patients were stratified into five groups by the initial percentage of band cells (neutrophils): 0%-10% (3358 patients), 10%-19% (849), 20%-29% (618), 30%-39% (347), and ≥ 40% (386). The groups varied significantly in terms of clinicodemographic characteristics, bacteremia profiles, and mortality rates at 3, 15, and 30 days. Overall, each 10% increase in the initial band percentage was independently associated with an average 12% increase in 30-day mortality rates. The positive association between initial band percentages and 30-day mortality rates remained consistent across predefined patient subgroups. CONCLUSIONS:A higher initial percentage of band cells is independently associated with a higher risk of short-term mortality in adults presenting to the ED with bacteremia.

BACKGROUND:Phenotype-desirable antimicrobial therapy (PDAT) has recently been proposed to improve prognosis in patients with Enterobacterales bacteraemia. However, focusing on overall bacteraemia, the association of prompt PDAT with short-term mortality and the risk of hospital-onset Clostridioides difficile infection (hCDI) remains uncertain. METHODS:Among treatment-naïve adults with community-onset bacteraemia, clinical variables were retrospectively collected. Etiologic pathogens were prospectively preserved to accurately determine the timepoints of effective antimicrobial therapy and PDAT initiation. After stratifying patients into four groups by PDAT delays (<2.0 d, 2.0-5.9 d, ≥6.0 d, and no PDAT), a time-dependent Cos-regression model was used to investigate the association of prompt PDAT with 30-d crude mortality and hCDI development, after, respectively adjusting for the independent predictors identified. RESULTS:Of the total 3815 patients, with the no-PDAT group (n = 195) as the reference, patients with PDAT delays of <2.0 d (n = 1819), 2.0-5.9 d (n = 1197), and ≥6 d (n = 604) were at significantly reduced risks of 30-d mortality and hCDI. For these categories, adjusted hazard ratios for 30-d mortality were 0.32, 0.35, and 0.63, respectively, and those for hCDI were 0.03, 0.19, and 0.44, respectively. Across all subgroups, prompt PDAT was consistently associated with reduced risks of 30-d mortality and hCDI development. CONCLUSIONS:Prompt PDAT was associated with reduced risks of short-term mortality and hCDI. These findings highlight the indispensability of the timely administration of pathogen-targeted narrow-spectrum antimicrobials, particularly in high-risk patients, and support the integration of this strategy into antimicrobial stewardship programmes.

Background Although inappropriate empirical antimicrobial therapy (IEAT) has been associated with increased mortality among patients with bloodstream infections (BSIs), comparative evidence regarding its prognostic impact between cirrhotic and non-cirrhotic patients remains limited. Methods Of the matched cohort study consisted of cirrhotic and non-cirrhotic adults with community-onset BSIs (CoBSIs), clinical covariables were retrospectively captured, and etiologic pathogens were prospectively stored for accurately determining IEAT. Effects of IEAT on 30-day crude mortality were assessed by time-dependent Cox-regression models among the cirrhotic and non-cirrhotic adults, with respective adjustment for multivariable mortality determinants. The prognostic effect of IEAT between cirrhotic and non-cirrhotic patients was compared using an interaction term analyzed in Cox-regression models, after propensity-score matching to balance the baseline covariates at the onset of BSIs between the two patient groups. Results Of 649 cirrhotic and 1294 non-cirrhotic adults with CoBSIs, the similarities in BSI severity, antimicrobial susceptibilities, and the proportion of IEAT were disclosed, but the 15- and 30-day crude mortality rates were higher among cirrhotic patients than those among non-cirrhotic patients. IEAT had a significant prognostic impact among the cirrhotic (adjusted hazard ratio [AHR], 1.69; P = 0.001) and non-cirrhotic (AHR, 1.49; P = 0.02) patients. In the matched cohort, a significant difference in the prognostic impact of IEAT between the cirrhotic (n = 353) and non-cirrhotic (n = 706) patients was exhibited (P = 0.012). Conclusions IEAT had more severe impacts on the short-term mortality of cirrhotic patients with CoBSIs, compared with those of non-cirrhotic patients.

BACKGROUND:Bacteremia remains associated with substantial morbidity, mortality, and healthcare costs. However, few studies have compared the associations between delays in key treatments, namely inappropriate empirical antimicrobial administration (IAEA) and delayed source control, and adverse clinical outcomes in patients with anaerobic bacteraemia versus those with aerobic bacteremia. METHODS:In this retrospective eight-year cohort study consisting treatment-naïve patients with community-onset bacteremia presenting to the emergency department, the association of delayed treatment and 30-day all-cause mortality were analyzed using Cox regression in survival curves, after adjusting for all independent mortality predictors. RESULTS:Of the total 5388 patients, those who received IAEA had a higher likelihood of 30-day mortality in both the anaerobic (adjusted hazard ratio [AHR], 3.16; P < 0.001) and aerobic (AHR, 1.51; P < 0.001) cohorts, compared with those who received appropriate administration of empirical antimicrobials. Of note, the association between IAEA and mortality was more pronounced among patients with anaerobic bacteremia than among those with aerobic bacteremia (P < 0.001). Focusing on 1508 patients with source-control-required bacteremia, compared with those with non-delay, delayed source control was associated with increased mortality rates in both the anaerobic (AHR, 11.53; P < 0.001) and aerobic (AHR, 7.82; P < 0.001) cohorts, with a significantly stronger prognosis association observed for anaerobic bacteremia (P = 0.008). CONCLUSIONS:Delayed administration of appropriate antimicrobials or delayed implementation of adequate source control was consistently associated with poorer short-term outcomes in bacteremia patients, particularly anaerobic bacteremia.

OBJECTIVE:The standard antimicrobial therapy for Clostridioides difficile infections (CDIs) is limited to oral fidaxomicin or vancomycin, but these agents are associated with high treatment failure and recurrence rates. Clostridium butyricum has been proven effective in many types of gastrointestinal disease. Due to its ability to not disrupt the gut microbiota, we hypothesized that the probiotic C. butyricum Miyairi produced bacteriocin (CBMB-B) can be a potential therapeutic agent against CDIs. METHODS:The inhibitory effects of CBM-B and vancomycin were compared using the kinetic time-kill assay, ex vivo co-culture model and mouse model. RESULTS:Among the clinical isolates of C. difficile, the minimal inhibitory concentration (MIC) of CBM-B ranged from 0.0625 to 8 µg/mL; the MIC50 and MIC90 were 1 µg/mL and 4 µg/mL, respectively. In a mouse model where the animals were infected with various C. difficile strains belonging to RT178 and receiving CBM-B intra-rectally, mice infected with isolates with a relatively low CBM-B MICs (2 µg/mL, abbreviated as M2) revealed significant better therapeutic effect, including less loss of body weight and cecum weight, compared with those infected with isolates of relative high CBM-B MICs (4 or 8 µg/mL, abbreviated as M4 or M8). The relative C. difficile bacterial burden in stool of mice receiving CBM-B treatment were significantly lower among mice infected with M2, compared with that infected with M4 or M8. CBMB treatment, compared with vancomycin therapy revealed less disturbance in gut microbiota. CONCLUSION:CBMB-B could be effective in the treatment of CDIs where infections were caused by C. difficile isolates with relative low MICs.

BACKGROUND:The human microbiome is increasingly recognized as a factor in cancer development, though its role in primary liver cancer (PLC) remains unclear. This retrospective cohort study examines tissue-specific microbiota differences between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and explores their association with tumor recurrence in PLC. METHODS:Clinical data from 116 patients (85 HCC and 31 age-matched CCA) were analyzed. Fresh frozen samples underwent RNAscope™ ISH assay for microbial RNA detection, while the MiSeq platform targeted 16 S ribosomal RNA. Microbiome functional pathways were explored with Tax4Fun2, and predictors of recurrence were identified through logistic regression analysis. RESULTS:Microbial RNA was detected within liver sinusoids, the basal lamina of intrahepatic bile ducts, and hepatocyte cytosol. 16 S ribosomal RNA analysis revealed differences in microbiome composition, including a distinct Firmicutes/Bacteroidetes ratio between CCA and HCC patients. Specific functional pathways were differentially enriched between the two groups. LEfSe and logistic regression analyses identified Aquabacterium spp. as a potential marker for HCC recurrence (OR, 14.77; 95 % CI, 1.07-203.94; p = 0.044). Increased abundances of Brevundimonas spp. (OR, 3.1 E+17; 95 % CI, 4.3 E+3-2.2 E+31; p = 0.013), Novosphingobium spp. (OR, 3.5 E+20; 95 % CI, 4.4 E+5-2.8 E+35; p = 0.007), and Pelomonas spp. (OR, 3.3 E+21; 95 % CI, 3.0 E+8-3.5 E+34; p = 0.001), along with decreased Staphylococcus spp. (OR 0.00; 95 % CI, 0.00-0.06; p = 0.003), were independent predictors of CCA occurrence. CONCLUSION:This study reveals that intratumoral microbiota help distinguish PLC subtypes and are associated with recurrence, identifying Aquabacterium as a potential marker for HCC recurrence and microbiome-based management.

BACKGROUND:The prognostic advantage of prompt antimicrobial therapy has been evidenced in patients experiencing bacteremia. When a specific bacteremia-etiologic pathogen is highly suspected or rapidly identified, studies addressing the question of how broad-spectrum antimicrobials should be administered based on local epidemiologic data and antibiograms are limited. OBJECTIVE:To determine the optimal antimicrobial susceptibility to support empirical prescribing decisions. METHODS:In the multicentric cohort study of adults with community-onset monomicrobial bacteremia, bacteremia-causing bacteria were prospectively collected to establish the antibiogram, and clinical information was retrospectively captured. Using Cox regression models after adjusting for independent predictors of mortality, the associations between administering antimicrobials with varied susceptibility categories and 30-day mortality were examined. RESULTS:For overall 5080 patients, significantly higher mortality risks were identified in the categories of <60% (adjusted hazard ratio [AHR], 2.47; p < 0.001), 60-69% (AHR, 1.68; p < 0.001), 70-79% (AHR, 1.55; p = 0.003), and ≥90% (AHR, 1.42; p = 0.03), compared with the reference category of 80-89%. For critically ill individuals, significantly higher mortality risks were disclosed in the categories of <60% (AHR, 2.92; p < 0.001), 60-69% (AHR, 2.17; p < 0.001), 70-79% (AHR, 2.09; p < 0.001), and 80-89% (AHR, 1.80; p = 0.003), compared with the reference category of ≥90% CONCLUSIONS: An optimal susceptibility range of 80-89% for empirical antimicrobial administration was determined to be significantly associated with a reduced risk of mortality. Critically ill patients might require a higher susceptibility threshold of ≥90%.

Objective:Clostridioides difficile is the most common cause of antibiotic-associated diarrhea. Wastewater from hospitals may be an important source of C. difficile transmission between hospitals and communities. The objective of this study is to quantify C. difficile spores and to elucidate their potential transmission risk via hospital wastewater. Methods:A prospective study of wastewater from a teaching hospital was conducted weekly, from July 2023 to June 2024. The number of C. difficile spores detected in wastewater from hospital settings fluctuated weekly during the study period. Results:There was a borderline association between the number of C. difficile spores detected in wastewater at room temperature in hospitals (p = 0.02) and the consumption of antimicrobial agents (p value = 0.04), particularly cephalosporins (p = 0.001). Specifically, the number of C. difficile spores detected in the wastewater was highly correlated with first-generation cephalosporin consumption (p = 0.002), particularly the consumption of first-generation intravenous cephalosporin (cefazolin) (p < 0.001). Conclusion:The number of C. difficile spores detected in wastewater from hospital settings is strongly associated with the consumption of antimicrobial agents, particularly cephalosporins. Further evaluation is needed to assess whether antibiotic stewardship programs can reduce the burden of C. difficile spores in wastewater.

BACKGROUND:Bloodstream infections (BSIs) are serious complications in hospitalized coronavirus disease 2019 (COVID-19) patients and may have worsened clinical outcomes. We evaluated clinical characteristics and outcomes of COVID-19 patients with BSI and compared them to a matched non-COVID-19 BSI cohort. METHODS:A retrospective cohort study was conducted at a tertiary medical center in southern Taiwan, and included adult patients hospitalized with concurrent COVID-19 and bloodstream infection (BSI) from January 2022 to April 2023. We compared survivors and non-survivors and assessed risk factors for in-hospital mortality. Propensity score matching (1:10) was used to compare COVID-19 BSI patients with non-COVID-19 BSI patients from 2017 to 2019. RESULTS:Among 104 COVID-19 patients with BSI, 26.0 % died during hospitalization. Male sex (adjusted OR (aOR) 5.87, 95 % confidence interval (CI) 1.51-22.83, p = 0.011), diabetes mellitus (aOR 3.89, 95 % CI 1.07-14.21, p = 0.040), Ct value ≤ 20 at diagnosis (aOR 5.15, 95 % CI 1.06-24.98, p = 0.042), Pitt bacteremia score ≥4 (aOR 5.84, 95 % CI 1.48-23.01, p = 0.012), and hospital-onset BSI (aOR 19.45, 95 % CI 3.33-113.54, p < 0.001) were independently associated with mortality. Hospital-onset BSI cases had higher rates of resistant and polymicrobial infections. Compared to non-COVID-19 BSI patients, COVID-19 BSI cases had more primary BSI and higher inappropriate empirical therapy use, though COVID-19 status itself was not independently associated with 30-day mortality after matching. CONCLUSIONS:BSIs in COVID-19 patients are linked to high mortality, particularly in hospital-acquired infections. Timely diagnosis, risk stratification, and targeted therapy remain crucial.

BACKGROUND:Antimicrobial therapy is the management cornerstone of patients with bloodstream infections (BSIs). We aimed to investigate the application of an antibiotic spectrum index (ASI) to assess hospital-onset Clostridioides difficile infection (hCDI) when treating individuals with BSIs. METHODS:In a retrospective multicenter cohort consisted of treatment-naïve and hospitalized adults experiencing community-onset BSIs, the association of ASIs and hCDI was recognized after adjusting for the independent predictors of hCDI. RESULTS:Of the total 2,966 patients, each day of prolonged antimicrobial therapy was associated with an average increase of 11% for the likelihood of hCDI; each additional 30 units of total ASIs was linked to an average increase of 146%; and each additional unit of daily ASIs was associated with an average increase of 22%. Notably, the total ASI demonstrated superior performance in predicting hCDI, as reflected by the area under the receiver operating characteristic curve (AUROC = 0.971), compared with the total duration of antimicrobial administration (AUROC = 0.956). CONCLUSIONS:The ASI metrics applied to assess hCDI episodes following the initiation of antimicrobial therapy in treating patients with community-onset BSIs proved effective. Accordingly, incorporating ASI-based assessments into antimicrobial stewardship programs might serve as a practical approach to mitigate hCDI risk.

Background: Infiltrative hepatocellular carcinoma (HCC) is often associated with an unfavorable prognosis, posing a challenge in determining the optimal therapeutic approach. Immunotherapy, employing immune checkpoint inhibitors (ICIs), has become a preferred first-line treatment for advanced HCC. However, the overall effectiveness of ICIs in patients with infiltrative HCC remains unclear. This study aims to compare the effect of ICI treatment on clinical outcomes between patients with infiltrative and non-infiltrative HCC. Materials and methods: A retrospective cohort consisting of unresectable HCC patients who underwent immunotherapy with ICIs, categorized into infiltrative and non-infiltrative groups was studied. Primary outcomes comprised treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, progression-free survival (PFS), and overall survival (OS). Results: Of 198 patients, 60 (30.3%) had infiltrative HCC, while 138 (69.7%) had non-infiltrative HCC. In the infiltrative group, the objective response rate (ORR) was 36.7% and the disease control rate (DCR) was 55.0%. For the non-infiltrative group, the ORR was 33.3% and the DCR was 56.5%, showing no significant difference between the two groups. However, patients in the infiltrative group had significantly shorter median of PFS and OS following immunotherapy, with a PFS of 4.1 months (95% CI: 2.5–6.7; p = 0.0409) and an OS of 10.4 months (95% CI: 6.7–14.4; p = 0.0268), compared with the non-infiltrative group, which had a PFS of 5.5 months (95% CI: 3.2–7.6) and an OS of 17.0 months (95% CI: 12.8–21.8). Conclusion: For immunotherapy, infiltrative HCC exhibits treatment responses similar to non-infiltrative HCC. Nonetheless, infiltrative HCC is associated with shorter survival outcomes, compared with non-infiltrative type. Our findings emphasize the essential of considering type discrepancies when developing management strategies for immunotherapy.

BACKGROUND:Machine learning (ML) techniques are increasingly being used in health outcome research to develop predictive models. However, ML models are often referred to as "black box models" because they lack interpretability. Our goal was to develop an ML model to predict mortality risk in patients with community-onset bacteremia. METHODS:We conducted a retrospective cohort study on 715 patients with bacteremia at a medical center in 2019. Model-agnostic methods were employed to visually explain the relationships between the predictors and the 30-day mortality risk. The model's performance was evaluated using the area under the receiver operating characteristic curve, calibration plots with the Brier score, accuracy, recall, precision, and F1 score. RESULTS:The top ten important predictors that significantly influenced the 30-day mortality prediction were the Pitt bacteremia score, septic shock, Charlson comorbidity index, length of stay in the ICU, neutrophil segment (%), age, neutrophil band (%), glucose, lymphocytes (%), and hemoglobin. The top three overall interaction strengths were septic shock, Charlson comorbidity index and Pitt bacteremia score, all of which significantly interacted with other predictors. CONCLUSION:ML revealed risk factors for 30-day mortality, including the Pitt bacteremia score, septic shock, age, pneumonia, and comorbidity, which also had multiple synergistic effects on 30-day mortality.

The potential performance of time-to-positivity (TTP) in predicting the prognosis of individuals experiencing Bloodstream infections (BSIs) has achieved little consensus. The retrospective cohort of 1015 treatment-naive adults with community-onset monomicrobial BSIs aimed to assess the performance of TTP and modified TTP (mTTP, TTP plus transportation time) in predicting 30-day mortality after adjusting for prognostic confounders, particularly the time-to-appropriate antibiotic (TtAa). Through Spearman's correlation, a significant linear-by-linear association (ρ = -0.943, P = 0.005) was exhibited between mTTP and 30-day mortality rates, but no significant association (ρ = -0.423, P = 0.26) was disclosed between TTP and 30-day mortality rates in the overall patient population. In the logistic regression model, each additional hour of mTTP or TTP was associated with an average decrease of 5 % (adjusted odds ratio [AOR], 0.95; P = 0.001) or 3 % (AOR, 0.97; P = 0.03) in the 30-day mortality rates, respectively, after adjusting for independent predictors of 30-day mortality. In conclusion, for adults with community-onset monomicrobial BSIs, mTTP revealed a favorable performance over TTP alone in predicting short-term mortality.

BACKGROUND:This article focuses on extracting a standard feature set for predicting the complications of diabetes mellitus by systematically reviewing the literature. It is conducted and reported by following the guidelines of PRISMA, a well-known systematic review and meta-analysis method. The research articles included in this study are extracted using the search engine "Web of Science" over eight years. The most common complications of diabetes, diabetic neuropathy, retinopathy, nephropathy, and cardiovascular diseases are considered in the study. METHOD:The features used to predict the complications are identified and categorised by scrutinising the standards of electronic health records. RESULT:Overall, 102 research articles have been reviewed, resulting in 59 frequent features being identified. Nineteen attributes are recognised as a standard in all four considered complications, which are age, gender, ethnicity, weight, height, BMI, smoking history, HbA1c, SBP, eGFR, DBP, HDL, LDL, total cholesterol, triglyceride, use of insulin, duration of diabetes, family history of CVD, and diabetes. The existence of a well-accepted and updated feature set for health analytics models to predict the complications of diabetes mellitus is a vital and contemporary requirement. A widely accepted feature set is beneficial for benchmarking the risk factors of complications of diabetes. CONCLUSION:This study is a thorough literature review to provide a clear state of the art for academicians, clinicians, and other stakeholders regarding the risk factors and their importance.

IntroductionAntimicrobial therapy plays a crucial role in the management of CDI patients. However, the standard agent for treating CDIs is limited to oral fidaxomicin or vancomycin. For patients made nil by mouth, there is a clinically urgent and essential need to develop an intravenous antibiotic.MethodsFor C. difficile with the lowest MIC of nemonoxacin and vancomycin, the inhibitory effects were tested using the kinetic time-kill assay and ex vivo co-culture model. The effectiveness of nemonoxacin and vancomycin in inhibiting spore germination, the sporicidal activity, and the treatment of mice with CDIs were compared.ResultsFor clinical isolates and laboratory strains, lower MICs of nemonoxacin against C. difficile than levofloxacin and ciprofloxacin were observed, even in those harboring point mutations in the quinolone-resistance determining region. Although nemonoxacin failed to suppress spore outgrowth and germination in C. difficile, it exhibited an effective inhibitory effect against C. difficile in the kinetic time-kill assay and the ex vivo co-culture model. Mice receiving intraperitoneal nemonoxacin had less weight loss, higher cecum weight, a longer colon length, and lower expression of the tcdB gene, compared with untreated mice. Notably, there were no significant differences observed in weight loss, cecum weight, colon length, or tcdB gene expression between mice treated with vancomycin and those treated with any dose of nemonoxacin. Similarly, no significant differences were found between mice receiving combination therapy of intraperitoneal nemonoxacin plus oral vancomycin and those treated with intraperitoneal nemonoxacin or oral vancomycin alone.DiscussionThe potential role of nemonoxacin, which can be administered parenterally, for treating CDIs was evidenced through the in vitro, ex vivo, and mouse models.

Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan–Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan–Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.

Fluoroquinolones are potentially active against Elizabethkingia anophelis. Rapidly increased minimum inhibitory concentrations (MICs) and emerging point mutations in the quinolone resistance-determining regions (QRDRs) following exposure to fluoroquinolones have been reported in E. anophelis. We aimed to investigate point mutations in QRDRs through exposure to levofloxacin (1 × MIC) combinations with different concentrations (0.5× and 1 × MIC) of minocycline, rifampin, cefoperazone/sulbactam, or sulfamethoxazole/trimethoprim in comparison with exposure to levofloxacin alone. Of the four E. anophelis isolates that were clinically collected, lower MICs of levofloxacin were disclosed in cycle 2 and 3 of induction and selection in all levofloxacin combination groups other than levofloxacin alone (all p = 0.04). Overall, no mutations were discovered in parC and parE throughout the multicycles inducted by levofloxacin and all its combinations. Regarding the vastly increased MICs, the second point mutations in gyrA and/or gyrB in one isolate (strain no. 1) occurred in cycle 2 following exposure to levofloxacin plus 0.5 × MIC minocycline, but they were delayed appearing in cycle 5 following exposure to levofloxacin plus 1 × MIC minocycline. Similarly, the second point mutation in gyrA and/or gyrB occurred in another isolate (strain no. 3) in cycle 4 following exposure to levofloxacin plus 0.5 × MIC sulfamethoxazole/trimethoprim, but no mutation following exposure to levofloxacin plus 1 × MIC sulfamethoxazole/trimethoprim was disclosed. In conclusion, the rapid selection of E. anophelis mutants with high MICs after levofloxacin exposure could be effectively delayed or postponed by antimicrobial combination with other in vitro active antibiotics.