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Objectives To investigate the characteristics and clonal dynamics of tigecycline-resistant Acinetobacter baumannii (TRAB) isolates from a Chinese hospital from 2016 to 2021. Methods A total of 64 TRAB isolates were screened and WGS was performed. Phylogenetic analysis and non-polymorphic mutation analysis were used to analyse their clonal dynamics and tigecycline resistance-related mutations. RT-PCR was used to analyse the expression of the resistance-nodulation cell-division (RND) efflux pump genes adeB and adeJ. Gene cloning was used to explore the effect of tet (39) variants on tigecycline resistance. Results Most TRAB isolates were found to be MDR, with 95% (61/64) of the isolates showing resistance to carbapenems. These TRAB isolates were classified into three primary genetic clusters based on core-genome SNPs. The KL2 cluster persisted throughout the study period, whereas the KL7 cluster emerged in 2019 and became the dominant clone. The KL7 cluster carried more antimicrobial resistance genes than the other two clusters. The predominant tigecycline resistance mechanism of the KL2 cluster and KL7 cluster was IS insertion in adeN (82.1%, 23/28) and genetic alterations in adeS (76.2%, 16/21), respectively. Eleven novel AdeS mutations were identified associated with elevated AdeB expression and tigecycline resistance. Moreover, we characterized a plasmid-borne tet (39) variant with an Ala-36-Thr substitution that synergizes with the RND efflux pump to confer high-level tigecycline resistance. Conclusions This work provides important insights into the diverse mechanisms associated with tigecycline resistance in A. baumannii , highlighting a pressing need for further monitoring of ST2-KL7 A. baumannii in clinical settings. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, the incidence of hypofibrinogenemia (HF) after tigecycline (TGC) treatment significantly exceeds the probability claimed by drug manufacturers. Objective: We aimed to identify the risk factors for TGC-associated HF and develop prediction and survival models for TGC-associated HF and the timing of TGC-associated HF. Methods: This single-center retrospective cohort study included 222 patients who were prescribed TGC. First, we used binary logistic regression to screen the independent factors influencing TGC-associated HF, which were used as predictors to train the extreme gradient boosting (XGBoost) model. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were used to evaluate the performance of the model in the verification cohort. Subsequently, we conducted survival analysis using the random survival forest (RSF) algorithm. A consistency index (C-index) was used to evaluate the accuracy of the RSF model in the verification cohort. Results: Binary logistic regression identified nine independent factors influencing TGC-associated HF, and the XGBoost model was constructed using these nine predictors. The ROC and calibration curves showed that the model had good discrimination (areas under the ROC curves (AUC) = 0.792 [95% confidence interval (CI), 0.668–0.915]) and calibration ability. In addition, DCA and CICA demonstrated good clinical practicability of this model. Notably, the RSF model showed good accuracy (C-index = 0.746 [95%CI, 0.652–0.820]) in the verification cohort. Stratifying patients treated with TGC based on the RSF model revealed a statistically significant difference in the mean survival time between the low- and high-risk groups. Conclusions: The XGBoost model effectively predicts the risk of TGC-associated HF, whereas the RSF model has advantages in risk stratification. These two models have significant clinical practical value, with the potential to reduce the risk of TGC therapy. [ABSTRACT FROM AUTHOR]

Background/Objectives: As a primary source of mortality and disability, bacterial infections continue to develop a severe threat to humanity. Nuclear medicine imaging (NMI) is known for its promising potential to diagnose deep-seated bacterial infections. This work aims to develop a new technetium-99m (99mTc) labeled tigecycline radiopharmaceutical as an infection imaging agent. Methods: Reduced 99mTc was used to make a coordinate complex with tigecycline at pH 7.7–7.9 at room temperature. Instantaneous thin-layer chromatography impregnated with silica gel (ITLC-SG) and ray detector equipped high-performance liquid chromatography (ray-HPLC) was performed to access the radiolabeling yield and radiochemical purity (RCP). Results: More than 91% labeling efficiency was achieved after 25 min of mild shaking of the reaction mixture. The radiolabeled complex was found intact up to 4 h in saline. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infection-induced rats were used to record the biodistribution of the radiopharmaceutical and its target specificity; 2 h' post-injection biodistribution revealed a 2.39 ± 0.29 target/non-target (T/NT) ratio in the E. coli infection-induced animal model, while a 2.9 ± 0.31 T/NT value was recorded in the S. aureus bacterial infection-induced animal model. [99mTc]Tc-tigecycline scintigraphy was performed in healthy rabbits using a single photon emission computed tomography (SPECT) camera. Scintigrams showed normal kidney perfusion and excretion into the bladder. Conclusion: In conclusion, the newly developed [99mTc]Tc-tigecycline radiopharmaceutical could be considered to diagnose broad-spectrum bacterial infections. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate antibiotic susceptibility and antimicrobial resistance trends among clinically significant anaerobes in Kuwait hospitals from 2013 to 2022, comparing these findings with data from 2002 to 2012. Methods: The study prospectively collected 2,317 anaerobic isolates from various body sites across four Kuwaiti hospitals between January 2013 and December 2022. The minimum inhibitory concentrations for 11 antianaerobic antibiotics were determined using E-test methodology. The study analyzed trends and resistance rates across two periods: 2013–2017 and 2018–2022, using statistical analysis for resistance comparison. Results: Of the 2,317 isolates, most were from wounds (42.2%), fluids (28.0%), and tissues (20.5%). Bacteroides fragilis was the most common pathogen (34.0%), followed by Prevotella bivia (13.4%). Over 90% of isolates were susceptible to imipenem, meropenem, tigecycline, and metronidazole, whereas lower susceptibility was observed for penicillin, amoxicillin–clavulanic acid, and clindamycin. Notable differences in resistance profiles since 2002 were observed, especially in amoxicillin–clavulanic acid, piperacillin, piperacillin–tazobactam, and clindamycin. Conclusion: Owing to detected resistance to all antibiotics, susceptibility testing for anaerobic isolates is recommended in severe infections to ensure effective antimicrobial therapy. Continuous surveillance is crucial for developing antibiotic policies to manage invasive anaerobic infections. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effectiveness and safety of using tigecycline as a salvage therapy in critically ill children who did not respond to other antibiotics. Methods We conducted a retrospective cohort analysis that included children who received tigecycline for at least 48 hours and four doses during their pediatric intensive care unit admission. Demographic and clinical features of the subjects were evaluated through a comprehensive review of medical records. The effectiveness of tigecycline was assessed by thoroughly evaluating clinical and microbiological outcomes. Results During the study period, 72 pediatric patients with 88 episodes of infection received tigecycline according to antimicrobial susceptibility in 62.5% of cases and empirically in 37.5%. The median duration of tigecycline therapy was 10 days (range, 2–33 days). Klebsiella pneumoniae (n = 17, 30.9%) was the most frequently isolated pathogen, followed by Acinetobacter baumannii (n = 10, 18.1%). Ventilator-associated pneumonia was the most common infection (n = 29). Of the 55 isolated pathogens, 43 were multidrug-resistant (MDR), and 2 were extensively drug-resistant (XDR) gram-negative bacteria. Clinical response and microbiological clearance were achieved in 42 and 50.9% of episodes, respectively. The overall mortality was 40.9%, with an attributable mortality rate of 29.5%. Conclusion Tigecycline could be used as a salvage therapy for critically ill pediatric patients infected with MDR or XDR pathogens in the lack of alternative treatment options. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs. A prospective study conducted at a tertiary care hospital in India during 2021–23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR. During the study period, predominantly (70 %) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1% to 79 %. Majority of the carbapenemase producers were metallo-β-lactamases (MBL) producers (75 %). Colistin resistance was noted in 5.4 % of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0–14 %), while resistance to newer β-lactam/β-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer β-lactam/β-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region. The escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance. [ABSTRACT FROM AUTHOR]

Tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) is increasing and has emerged as a global public health issue. However, the mechanism of tigecycline resistance remains unclear. The objective of this study was to investigate the potential role of efflux pump system in tigecycline resistance. 29 tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) strains were collected and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The ramR, acrR, rpsJ, tet(A), and tet(X) were amplified by polymerase chain reaction (PCR). The mRNA expression of different efflux pump genes and regulator genes were analyzed by real-time PCR. Additionally, KP14 was selected for genome sequencing. KP14 genes without acrB, oqxB, and TetA were modified using suicide plasmids and MIC of tigecycline of KP14 with target genes knocked out was investigated. It was found that MIC of tigecycline of 20 out of the 29 TNSKP strains decreased by over four folds once combined with phenyl-arginine-β-naphthylamide dihydrochloride (PaβN). Most strains exhibited upregulation of AcrAB and oqxAB efflux pumps. The strains with acrB, oqxB, and tetA genes knocked out were constructed, wherein the MIC of tigecycline of KP14∆acrB and KP14∆tetA was observed to be 2 µg/mL (decreased by 16 folds), the MIC of tigecycline of KP14ΔacrBΔTetA was 0.25 µg/mL (decreased by 128 folds), but the MIC of tigecycline of KP14∆oqxB remained unchanged at 32 µg/mL. The majority of TNSKP strains demonstrated increased expression of AcrAB-TolC and oqxAB, while certain strains showed mutations in other genes associated with tigecycline resistance. In KP14, both overexpression of AcrAB-TolC and tet(A) gene mutation contributed to the mechanism of tigecycline resistance. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To construct the automatic surveillance module for coagulation dysfunction complicated with bleeding events based on adverse drug events active surveillance and assessment system (ADE-ASAS-II), and to explore an automated method for monitoring adverse drug reactions (ADR) under complex diagnostic conditions. METHODS: Taking tigecycline as a case study, a quantitative-text composite monitoring module was constructed through the combination of trigger technology and natural language processing technology based on decision tree algorithm, and the coagulation dysfunction-associated bleeding events were mined based on the hospital information system (HIS) data of a large grade III, level A hospital. The module settings were optimized iteratively, and the manual evaluation results were used as the "gold standard" to compare the monitoring performance of modules under different optimization schemes to determine the optimal settings. The incidence of positive events and their basic characteristics were calculated. RESULTS: A total of 2 345 patients using tigecycline were monitored from 2019 to 2022 were monitored, and 83 positive cases were identified after manual evaluation. Under the initial module setting, 985 cases were alarmed, with a precision rate of 7. 72%, a recall rate of 91. 57% and F1 value of 14. 23%. After iterative optimization, 475 cases were alarmed, the recall rate was stable, the precision rate was increased to 16. 00% and the F1 value was increased to 27. 24%; 1 870 cases were marked as negative cases by ADE-ASAS-II, which had reduced approximately 80% of the manual evaluation workload. Of the 1 359 patients who met the inclusion and exclusion criteria (1 276 negative cases and 83 positive cases), the incidence of coagulation dysfunction complicated with bleeding events was 6. 11%. CONCLUSIONS: The development of the module of coagulation dysfunction complicated with bleeding events has improved the detection efficiency of ADE-ASAS-II for ADR under complex diagnostic conditions, and has expanded the monitoring method for identifying ADR by combining structured and unstructured HIS data. Subsequent expansion of the sample is needed to verify the stability of the module and to continuously improve the system algorithm, so as to further enhance the monitoring efficiency. [ABSTRACT FROM AUTHOR]

Objective: Pakistan bears most of the burden of drug-resistant typhoid, challenging its healthcare systems with substantial cost. This study’s purpose is to investigate resistance in community-acquired salmonella typhi to guide its evidence-based empiric treatment. Material & Methods: This study used retrospective data from the microbiology laboratory, Khyber Teaching Hospital, Peshawar (September 2022-March 2023). Data of routine diagnostic samples for typhoid was retrieved from the database. Kirby– Bauer disk diffusion method was employed to determine the sensitivity of S. Typhi against a panel of 21 selected antibiotic discs (not exclusively for each isolate). Results: Among 1742 suspected patients, 239 (13.92%) were positive for S. Typhi with 212/238 (89.1%), 227/233 (97.4%), and 196/239 (82.0%) isolates resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, respectively. High resistance (88.0% to ciprofloxacin) was detected against fluoroquinolones. Third-generation cephalosporins also showed poor activity with 144/158 (91.1%) and 120/136 (88.2%) resistance towards ceftriaxone and cefixime, respectively, except for cefoperazone/sulbactam (2/123, 1.6%). Among 157 tested isolates, 3 (1.9%), 9 (5.7%), and 123 (78.3%) were labeled as non-resistant, MDR, and XDR strains, respectively. XDRs were less resistant to azithromycin (1/114), piperacillin/tazobactam (1/123), carbapenems (0/123), and tigecycline (0/123). Conclusion: XDR S. Typhi was observed as the dominant strain in Peshawar regions for which azithromycin is still the drug of choice. With emerging resistance, azithromycin safety should be ensured through antibiotic stewardship principles. An interesting finding was the enhanced activity of cefoperazone/sulbactam, suggesting future studies. Alternative options are expensive antibiotics which can be used as a last resort. [ABSTRACT FROM AUTHOR]

Tetracyclines constitute a unique class of antibiotic agents, widely prescribed for both community and hospital infections due to their broad spectrum of activity. Acting by disrupting protein synthesis through tight binding to the 30S ribosomal subunit, their interference is typically reversible, rendering them bacteriostatic in action. Resistance to tetracyclines has primarily been associated with changes in pump efflux or ribosomal protection mechanisms. To address this challenge, tetracycline molecules have been chemically modified, resulting in the development of third-generation tetracyclines. These novel tetracyclines offer significant advantages in treating infections, whether used alone or in combination therapies, especially in hospital settings. Beyond their conventional antimicrobial properties, research has highlighted their potential non-antibiotic properties, including their impact on immunomodulation and malignancy. This review will focus on third-generation tetracyclines, namely tigecycline, eravacycline, and omadacycline. We will delve into their mechanisms of action and resistance, while also evaluating their pros and cons over time. Additionally, we will explore their therapeutic potential, analyzing their primary indications of prescription, potential future uses, and non-antibiotic features. This review aims to provide valuable insights into the clinical applications of third-generation tetracyclines, thereby enhancing understanding and guiding optimal clinical use. [ABSTRACT FROM AUTHOR]

Backgroud: Although not fully investigated, studies show that Legionella pneumophila can develop antibiotic resistance. As there is limited data available for Portugal, we determined the antibiotic susceptibility profile of Portuguese L. pneumophila serogroup 1 (LpnSg1) isolates against antibiotics used in the clinical practice in Portugal. Methods: Minimum inhibitory concentrations (MICs) were determined for LpnSg1 clinical (n = 100) and related environmental (n = 7) isolates, collected between 2006–2022 in the context of the National Legionnaire´s Disease Surveillance Programme, against azithromycin, clarithromycin, erythromycin, levofloxacin, ciprofloxacin, moxifloxacin, rifampicin, doxycycline, tigecycline, and amoxicillin/clavulanic acid, using three different assays. Isolates were also PCR-screened for the presence of the lpeAB gene. Results: Twelve isolates had azithromycin MICs above the EUCAST tentative highest WT MIC, 9 of which were lpeAB negative; for erythromycin and clarithromycin, all isolates tested within the susceptible range. The number of isolates with MICs above the tentative highest WT MIC for the remaining antibiotics was: ciprofloxacin: 7; levofloxacin: 17; moxifloxacin: 8; rifampicin: 11; doxycycline: 82; tigecycline: 4. EUCAST breakpoints are not available for amoxicillin/clavulanic acid. We estimated the ECOFFs and one isolate had a MIC eightfold higher than the E-test ECOFF. Additionally, a clinical isolate generated three colonies growing on the E-test inhibition zone that resulted in MICs fourfold higher than for the parental isolate. Conclusions: We report, for the first time, elevated MICs against first-line and other antibiotics (including azithromycin, fluoroquinolones and amoxicillin/clavulanic acid commonly used to treat pneumonia patients in Portugal) in Portuguese L. pneumophila strains. Results point towards decreased susceptibility in circulating strains, justifying further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Tigecycline has a broad spectrum of activity, including activity against drug-resistant Gram-positive and -negative microorganisms. Its side effects are significant, but hypoglycemia is a rare finding during treatment. We aim to present an event of severe hypoglycemia in a patient with type 2 diabetes mellitus with replacement renal therapy, and hemodialysis after initiating tigecycline. Case presentation: A 54-year-old female diagnosed with type 2 diabetes mellitus was under treatment with basal-bolus insulin therapy and oral antihypertensive drugs. She started hemodialysis 24 months ago. She complained of recurrent fever for the last seven months and was treated with several antibiotics. In two separate blood cultures, she tested positive for methicillin-resistant Staphylococcus epidermidis (MRSE). Based on the antibiogram, we started treatment with tigecycline 100 mg/day. After 6-8 hours from the first dose, the patient is complicated with events of hypoglycemia and then continues with severe hypoglycemia (40-47 mg/dL). The patient continued to have hypoglycemia for about 16-18 hours after the last dose. We didn't find any reasons to explain the cause of episodes of hypoglycemia. She did not have high blood insulin levels (insulin 4.11 mIU/L [range 2.6-24.9]). We followed her for six months and the patient did not experience episodes of hypoglycemia. Conclusions: The association of severe hypoglycemia with tigecycline treatment is a very rare event and published papers on this topic are limited. Clinicians should be aware of this rare event when administering tigecycline and should routinely check blood glucose level during the treatment. [ABSTRACT FROM AUTHOR]

Blood flow infections (BSIs) is common occurrences in intensive care units (ICUs) and are associated with poor prognosis. The study aims to identify risk factors and assess mortality among BSI patients admitted to the ICU at Shanghai Ruijin hospital north from January 2022 to June 2023. Additionally, it seeks to present the latest microbiological isolates and their antimicrobial susceptibility. Independent risk factors for BSI and mortality were determined using the multivariable logistic regression model. The study found that the latest incidence rate of BSI was 10.11%, the mortality rate was 35.21% and the mean age of patients with BSI was 74 years old. Klebsiella pneumoniae was the predominant bacterial isolate. Logistic multiple regression revealed that tracheotomy, tigecycline, gastrointestinal bleeding, shock, length of hospital stay, age and laboratory indicators (such as procalcitonine and hemoglobin) were independent risk factors for BSI. Given the elevated risk associated with use of tracheotomy and tigecycline, it underscores the importance of the importance of cautious application of tracheostomy and empirical antibiotic management strategies. Meanwhile, the independent risk factors of mortality included cardiovascular disease, length of hospital stay, mean platelet volume (MPV), uric acid levels and ventilator. BSI patients exhibited a significant decrease in platelet count, and MPV emerged as an independent factor of mortality among them. Therefore, continuous monitoring of platelet-related parameters may aid in promptly identifying high-risk patients and assessing prognosis. Moreover, monitoring changes in uric acid levels may serve as an additional tool for prognostic evaluation in BSI patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the effects of tigecycline on coagulation function and liver function. METHODS: Clinical data of 55 patients receiving anti-infective treatment with tigacycline in Beijing Friendship Hospital, Capital Medical University from Jan. 2019 to Jun. 2022 were collected. Levels of coagulation function indicators including peripheral blood fibrinogen ( FIB), activated partial thrombin time ( APTT), international normalized ratio ( INR), D-dimer and platelet count ( PLT) were recordedbefore medication ( T0 ), 7 d after medication ( T7 ) and at the end of medication ( Tf ). The levels of liver function indicators in T0, T7 and Tf were recorded, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin (ALB). The coagulation function and liver function indicators were statistically analyzed. RESULTS: After treatment with tigecycline, the FIB level of patients showed a decreasing trend, and the FIB level of T7 and Tf was lower than that of T0, with statistically significant difference (P<0. 05); the APTT of T7 and Tf was longer than that of T0, the difference was statistically significant ( P < 0. 05); the D-dimer level showed a decreasing trend, and the D-dimer level of Tf was lower than that of T0, with statistically significant difference ( P < 0. 05), suggesting that tigecycline had some effects on coagulation function. After treatment with tigecycline, ALT levels of T7 and Tf were lower than those of T0, the difference was statistically significant (P<0. 05), showing a decreasing trend; the levels of ALP, AST, TBIL and ALB in T7 and Tf were not significantly different from those in T0, without statistically significant differences (P>0. 05), suggesting that tigecycline had no effect on liver function. CONCLUSIONS: Tigecycline may cause a decrease in FIB levels, prolongation of APTT, and a decrease in D-dimer levels, and patients’ coagulation needs to be closely monitored during administration to prevent bleeding. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the mechanism of tigecycline resistance in Escherichia coli that is mediated by the tet (A) variant gene. Methods E. coli strain 573 carried a plasmid-borne tet (A) variant gene, tentatively designated tet (A)TIG, that conferred decreased tigecycline susceptibility (MIC 0.5 mg/L). When exposed to increasing concentrations of tigecycline (0.25–8 mg/L), mutants growing at 2, 4 and 8 mg/L were obtained and sequenced. Copies of plasmid and tet (A)TIG relative to the chromosomal DNA in the mutants were determined by WGS and quantitative PCR (qPCR). Expression of tet (A)TIG in the mutants was evaluated by RT–qPCR. The tet (A)TIG-carrying plasmids were visualized by S1-PFGE and Southern blot hybridization. PCR served for the detection of a tet (A)TIG-carrying unconventional circularizable structure (UCS). Results Tigecycline resistance with maximum MICs of 16 mg/L was seen in E. coli mutants selected in the presence of tigecycline. Compared with the parental strain, the relative copy number and transcription level of tet (A)TIG in the mutants increased significantly in the presence of 2, 4 and 8 mg/L tigecycline, respectively. With increasing tigecycline selection pressure, the tet (A)TIG-carrying plasmids in the mutants increased in size, correlating with the number of tandem amplificates of a ΔTn As1 -flanked UCS harbouring tet (A)TIG. These tandem amplificates were not stable in the absence of tigecycline. Conclusions Tigecycline resistance is due to the tandem amplification of a ΔTn As1 -flanked tet (A)TIG-carrying plasmid-borne segment in E. coli. The gain/loss of the tandem amplificates in the presence/absence of tigecycline represents an economic way for the bacteria to survive in the presence of tigecycline. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea in the United States. Tigecycline has been proposed as a potential treatment for CDI, though limited clinical data exist to support this practice. The objective of this study was to determine if the provision of tigecycline provides a clinically meaningful benefit to inpatients with CDI. This study was a retrospective chart review enrolling inpatients receiving treatment for CDI. Patients were divided into cohorts depending on whether they received a standard antibiotic therapy regimen for CDI or an antibiotic treatment regimen that included tigecycline. The primary outcome was clinical recovery at the time of hospital discharge. A total of 39 and 22 patients were included in the standard antibiotic therapy and tigecycline groups, respectively. ATLAS (Age, Treatment, Leukocyte, Albumin, Serum creatinine) scores at the time of CDI diagnosis were similar between the two groups, though patients in the tigecycline groups were more likely to represent a recurrent episode of CDI. There was no difference in the rate of clinical recovery at the time of hospital discharge between the standard antibiotic therapy and tigecycline groups (38.5% vs. 36.4%, p = 0.8710). These data do not support the routine use of tigecycline for the treatment of CDI, though interpretation is limited due to baseline differences between groups and the retrospective, observational nature of this study. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is considered as the most common pathogen of hospital-acquired pneumonia. K. pneumoniae has emerged as the superbug which had shown multidrug resistance (MDR) as well as extensively drug resistance. Carbapenem resistant K. pneumoniae (CRKP) has become a menace for the treatment with monotherapy of the patients mainly admitted in intensive care units. Hence, in the present study we collected total 187 sputum isolates of K. pneumoniae and performed the antimicrobial susceptibility testing by using the automated Vitek-2 system and broth micro-dilution method (67 CRKP). The combination study of solithromycin with meropenem, colistin, cefotaxime, piperacillin and tazobactam, nitrofurantoin, tetracycline, levofloxacin, curcumin and nalidixic acid was performed by using checkerboard assay. We observed the high rate of resistance towards ampicillin, cefotaxime, ceftriaxone, cefuroxime and aztreonam. The colistin and tigecycline were the most sensitive drugs. The CRKP were 36%, maximum were from the patients of ICUs. The best synergistic effect of solithromycin was with meropenem and cefotaxime (100%), colistin and tetracycline (80%). So, these combinations can be a choice of treatment for the infections caused by MDR CRKP and other Gram-negative bacteria where the monotherapy could not work. [ABSTRACT FROM AUTHOR]

Background: A novel plasmid-mediated resistance–nodulation–division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the post-antibiotic era, including the "last-resort" antibiotic tigecycline. Results: In this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance. Galleria mellonella and mouse infection models in vivo further revealed that harmaline is a promising candidate to reverse tigecycline resistance. Inspiringly, harmaline works synergistically with tigecycline by undermining tmexCD1-toprJ1-mediated multidrug resistance efflux pump function via interactions with TMexCD1-TOprJ1 active residues and dissipation of the proton motive force (PMF), and triggers a vicious cycle of disrupting cell membrane integrity and metabolic homeostasis imbalance. Conclusion: These results reveal the potential of harmaline as a novel tigecycline adjuvant to combat hypervirulent K. pneumoniae infections. [ABSTRACT FROM AUTHOR]

Background Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: −0.89 days (95% confidence interval [CI], −1.38 to −.41); linezolid: −0.89 days (95% CI, −1.27 to −.52); meropenem: −0.97 days (95% CI, −1.39 to −.56); tigecycline: −1.41 days (95% CI, −2.19 to −.63); P <.001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (−43.49; 95% CI, −58.61 to −28.37; P <.001), tigecycline (−35.47; 95% CI, −44.94 to −26.00; P <.001), and daptomycin (−9.47; 95% CI, −15.25 to −3.68; P =.002). Discussion A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records. [ABSTRACT FROM AUTHOR]

Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment. [ABSTRACT FROM AUTHOR]

To determine whether mortality is lower in patients with Klebsiella pneumoniae bloodstream infection (BSI) who receive combination antimicrobial therapy than in those who receive monotherapy. Two authors independently searched for relevant articles in the PubMed, Embase, Web of Science, and Cochrane Library databases through to August 10, 2023. Risk of bias was evaluated using the ROBINS-I tool. Possible sources of heterogeneity were evaluated by meta-regression using a mixed-effects model. Among 8044 articles screened, there were 23 studies (3443 patients) that were eligible for meta-analysis. Meta-regression analysis identified the proportion of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI to be a potential source of heterogeneity. Subgroup analysis showed that mortality on monotherapy was significantly higher when the proportion of patients with CRKP BSI was ≥50% (OR 1.75, 95% CI 1.33–2.30) and significantly lower when this proportion was <50% (OR 0.55, 95% CI 0.24–1.24). Overall mortality was significantly higher on tigecycline monotherapy (OR 2.86, 95% CI 1.46–5.59) than on combination therapy containing both these agents. There was a trend in favor of colistin/polymyxin B-containing combination therapy (OR 1.37, 95% CI 0.83–2.28). Combination antimicrobial therapy can lower mortality in patients with CRKP but may not show a survival advantage over monotherapy when the proportion of patients with CRKP BSI is <50%. High-quality prospective observational studies are needed because of the high risk of bias and limited data in the studies performed to date. • The studies reported to date have shown that combination therapy, most commonly tigecycline-containing, colistin/polymyxin B-containing is associated with lower mortality when treating CRKP. • A trend of higher mortality was observed on combination therapy in the <50% CRKP group. • In addition, we found that mortality was lower on tigecycline-based combination therapy than on tigecycline monotherapy (four studies, 206 patients). [ABSTRACT FROM AUTHOR]

Objective Ventriculitis is an example of the increasing global trend in difficult-to-treat infections in neonates caused by pathogens resistant to conventional therapies. This article describes the first use of intravenous and intraventricular tigecycline to treat ventriculitis caused by vancomycin-resistant enterococci in a preterm neonate and systematically review the literature on challenges posed by the definitions, diagnosis, and treatment of neonatal ventriculitis Methods The authors searched PubMed and Internet search engines for "ventriculitis" in the period from 2003 to 2023 restricting the research to "Newborn," "Human," "English language," and "full-text availability." Results Thirty-seven publications (20 case reports, 6 case series, and 11 research articles) were extracted upon research. Preterm birth, posthemorrhagic ventricular dilatation requiring placement of ventricular access devices, and sepsis preceded neonatal ventriculitis. Infections caused by rare microorganisms, in particular gram-negative bacteria resistant to conventional therapies, predominated in the publications describing the need for a combination of intravenous (IV) and intraventricular (IVT) therapies. Survivors of neonatal ventriculitis developed neurodevelopmental impairments such as hydrocephalus, seizures, motor function, hearing, and vision impairment. Conclusion Clinical suspicion of ventriculitis indicated by subtle signs is key for prompt diagnosis. Effective IV and IVT antibiotics are essential to prevent serious sequelae and mortality. The drug delivery method should be changed if there is no clinical response. This study emphasizes the urgent need for pediatric trials of antibiotics against organisms resistant to other drugs. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses a global threat to human health. Analyzing monitoring data on antimicrobial resistance can assist clinicians in making strategic decisions and promptly identifying outbreaks of antimicrobial-resistant organisms. The China Antimicrobial Surveillance Network (CHINET) was established in 2004 to monitor the trends in bacterial epidemiology and antimicrobial resistance. In this study, we analyzed the distribution and changing antimicrobial resistance profiles of Enterobacter spp. isolated from 53 hospitals across China between 2015 and 2021 using the CHINET data. Over the seven-year period, a total of 37,966 clinical isolates of Enterobacter spp. were obtained, accounted for 2.5% of all isolates and 5.7% of Enterobacteriaceae isolates. Among those isolates, Enterobacter cloacae was the most prevalent, comprising 93.7% (35,571/37,966). The majority of strains were isolated from respiratory tract samples (44.6%), followed by secretion, pus (16.4%), and urine samples (16.0%). As for patient composition, 37,966 Enterobacter spp. strains were predominantly isolated from inpatients (92.9%), whereas 7.1% were isolated from outpatients and emergency patients. Among inpatients, isolates from patients in surgical ward accounted for the highest percentage (24.4%). E. cloacae exhibited the lowest rates of resistance to amikacin, tigecycline, polymyxin B, imipenem, and meropenem (resistance rates < 8%). However, the percentage of carbapenem-resistant Enterobacter spp. was 10.0%, presenting a rising tendency over the 7-year study period. Antimicrobial resistance profiles of Enterobacter spp. isolates varied according to the department of isolation and patient age (adult or child), with the intensive care unit having the highest proportion of carbapenem-resistant Enterobacter spp. isolates. [ABSTRACT FROM AUTHOR]

Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use. • Patients undergoing tigecycline treatment are prone to low fibrinogen levels. • High incidence of hypofibrinogenemia is associated with the use of tigecycline. • Tigecycline can elevate INR levels without causing bleeding events or risk. • The 30-day mortality rate did not differ between the groups. [ABSTRACT FROM AUTHOR]

Objective: In recent years, the number of Gram-negative bacteria (GNB) resistant to ceftazidime-avibactam (CZA) isolated from clinic has been increasing. We aimed to evaluate the clinical efficacy in patients with CZA-resistant GNB infections, and analyze the risk factors for clinical treatment failure and death. Methods: Clinical data of patients with CZA-resistant GNB infections were collected retrospectively, and the influencing factors were analyzed by binary logistic regression. Results: A total of 75 patients with CZA-resistant GNB infections were enrolled in the study, and the clinical effective rate was 56% (42/75). Multivariate analysis showed that continuous renal replacement therapy (CRRT) during anti-infection treatment was an independent risk factor for clinical treatment failure (OR 0.177, 95% CI 0.05-0.63, p < 0.008). The 28-day mortality rate in 75 patients was 18.7% (14/75). Multivariate analysis showed that the regimen of colistin E 750,000 U q12h (OR 0.020, 95% CI 0.00-0.56, p < 0.021), co-administration of tigecycline (OR 8.851, 95% CI 2.38-1316.87, p < 0.012) and CRRT during anti-infection treatment (OR 79.610, 95% CI 4.87-1300.26, p < 0.002) were independent affecting factors for 28-day mortality in patients with CZAresistant GNB infections. Conclusions: Patients with CZA-resistant GNB infections had a higher possibility of clinical treatment failure and death. The results of the study based on small sample size from a single center showed that clinical treatment failure and death were more likely to happen in patients on CRRT, and the regimen of colistin E 750,000 U q12h or co-administration of tigecycline may reduce or increase mortality, respectively. Further validation in rigorously designed multicenter clinical studies with larger sample sizes is needed. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood–brain barrier (BBB). In this study, we prepared a novel core–shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation. [ABSTRACT FROM AUTHOR]

Tigecycline has been regarded as one of the most important last-resort antibiotics for the treatment of infections caused by extensively drug-resistant (XDR) bacteria, particularly carbapenem- and colistin-resistant Klebsiella pneumoniae (C-C-RKP). However, reports on tigecycline resistance have been growing. Overall, ~ 4000 K. pneumoniae clinical isolates were collected over a five-year period (2017–2021), in which 240 isolates of C-C-RKP were investigated. Most of these isolates (91.7%) were resistant to tigecycline. Notably, a high-risk clone of ST16 was predominantly identified, which was associated with the co-harboring of blaNDM-1 and blaOXA-232 genes. Their major mechanism of tigecycline resistance was the overexpression of efflux pump acrB gene and its regulator RamA, which was caused by mutations in RamR (M184V, Y59C, I141T, A28T, C99/C100 insertion), in RamR binding site (PI) of ramA gene (C139T), in MarR (S82G), and/or in AcrR (L154R, R13Q). Interestingly, four isolates of ST147 carried the mutated tet(A) efflux pump gene. To our knowledge, this is the first report on the prevalence and mechanisms of tigecycline resistance in C-C-RKP isolated from Thailand. The high incidence of tigecycline resistance observed among C-C-RKP in this study reflects an ongoing evolution of XDR bacteria against the last-resort antibiotics, which demands urgent action. [ABSTRACT FROM AUTHOR]

Background: Carbapenem‑resistant Acinetobacter baumannii (CRAB) is a serious global health challenge. It is increasingly associated with nosocomial infections and outbreaks in healthcare facilities. This study was conducted in a tertiary care teaching hospital in Jaipur to quantitate the burden of CRAB in our setup, examine the clinico‑epidemiological profile of patients infected with this bug, and determine their antibiotic susceptibility pattern. Methods: Clinical specimens collected from patients admitted in various wards and ICUs were processed. Bacterial identification and susceptibility testing were done using standard laboratory techniques and VITEK 2 automated system. Only one isolate per patient was included for study purposes. The data on the sociodemographic and epidemiological profile was collected and analyzed statistically. Results: A total of 4897 clinical samples were received in the department of microbiology during the study period, out of which 1517 exhibited significant growth, sample positivity rate being 31%. Acinetobacter baumannii was the third most common gram‑negative isolate (228/1067; 21.3%). Out of the total 228 A. baumannii isolates, 221 (97%) were carbapenem resistant. The maximum number of CRAB isolates were obtained from endotracheal secretions (103), followed by blood (59). All patients were critically ill and needed intensive care. The antibiotic susceptibility testing of these clinical isolates revealed a high level of resistance (99%) against ceftazidime, meropenem, and imipenem with the least resistance against colistin (2%) and tigecycline (9%). Conclusions: CRAB is an important global pathogen contributing to increased morbidity and mortality in hospitalized patients. Viable treatment options that may be used with success against bugs include minocycline, tigecycline, and polymyxins. [ABSTRACT FROM AUTHOR]

The article presents a case of pediatric Mycobacterium abscessus mastoiditis resistant to standard treatments, emphasizing the importance of considering M. abscessus in treatment-resistant chronic otitis media and mastoiditis, especially in children with tympanostomy tubes. Topics include challenges in diagnosing M. abscessus infections, treatment strategies, and the effectiveness of tigecycline in multidrug regimens.

Objective: This study aimed to identify subspecies of Mycobacterium abscessus complex (MABC) isolates from clinical samples by a molecular technique and to determine mutations responsible for macrolide and aminoglycoside resistance. We also aimed to investigate the correlation of phenotypic and molecular test results by examining the resistance to antimicrobial agents according to CLSI standard using the liquid microdilution test. Methods: 27 MABC isolates from clinical samples were examined. Molecular subspecies identification and mutations responsible for aminoglycoside (rrs mutation) and macrolide resistance (rrl mutation) were determined using the GenoType NTM-DR test. The resistance phenotypes of the strains to various antimicrobial agents were investigated by the Sensititre™ RAPMYCOI AST microdilution test. Results: Of the 27 isolates tested, 21 were M. abscessus subsp. abscessus, three were M. abscessus subsp. bolletii, and three were M. abscessus subsp. massiliense; rrs and rrl mutations were not observed in any strains. Except for one isolate, all M. abscessus subsp. abscessus strains showed the erm(41) T28 genotype, which indicates inducible macrolide resistance. The correlation between the GenoType NTM-DR and phenotypic susceptibility test results was 81% (k=0.5, p=0.02) for inducible macrolide resistance and 89% for acquired macrolide resistance. The most effective antimicrobial agents were amikacin, cefoxitin, imipenem, linezolid, and tigecycline. Conclusion: Although the GenoType NTM-DR test is reliable in identifying and detecting molecular macrolide and aminoglycoside resistance, there were discrepancies in the results. We recommend confirming the results with the phenotypic susceptibility method after growth on culture. Although the M. abscessus complex is resistant to many antimicrobial agents, it has shown high sensitivity to amikacin, cefoxitin, imipenem, linezolid, and tigecycline. High levels of inducible macrolide resistance in isolates indicate the importance of subtyping and sensitivity testing of isolates in patients where culture conversion has not been achieved. [ABSTRACT FROM AUTHOR]

Introduction: Mediastinitis remains one of the most serious complications of cardiac surgery. The reported incidence is 1-4%, while the related mortality varies from 10-47%. Case Presentation: A patient with triple vessel disease (TVD) was hospitalized at our clinic for coronary artery bypass graft (CABG) surgery. The preoperative examination results were normal. We performed standard CABG under extracorporeal circulation. The patient had a favorable postoperative course. On the fifth postoperative day, the wound showed seropurulent drainage. The treatment of the patient's wound continued with open dressing, negative wound pressure device, debridement, minimal muscle plasticity, and total bilateral muscle pectoral flap plasticity. The infecting microorganism was identified as multidrug-resistant Acinetobacter baumani, and systemic antibiotic therapy was initiated. The patient had "per secundum closure" of the wound after all these efforts. The wound healed completely 2 months after discharge, and the patient was in good health. Conclusions: Mediastinitis is associated with high mortality and high financial and human costs. The occurrence of this high-risk complication can be prevented through constant vigilance at every step from admission to discharge. [ABSTRACT FROM AUTHOR]

The presence of sub-minimal inhibitory concentration (sub-MIC) antibiotics in our environment is widespread, and their ability to induce antibiotic resistance is inevitable. Acinetobacter baumannii, a pathogen known for its strong ability to acquire antibiotic resistance, has recently shown clinical resistance to the last-line antibiotic tigecycline. To unravel the complex mechanism of A. baumannii drug resistance, we subjected tigecycline-susceptible, -intermediate, and -mildly-resistant strains to successive increases in sub-MIC tigecycline and ultimately obtained tigecycline-resistant strains. The proteome of both key intermediate and final strains during the selection process was analyzed using nanoLC-MS/MS. Among the more than 2600 proteins detected in all strains, we found that RND efflux pump AdeABC was associated with the adaptability of A. baumannii to tigecycline under sub-MIC pressure. qRT-PCR analysis also revealed higher expression of AdeAB in strains that can quickly acquire tigecycline resistance compared with strains that displayed lower adaptability. To validate our findings, we added an efflux pump inhibitor, carbonyl cyanide m-chlorophenyl hydrazine (CCCP), to the medium and observed its ability to inhibit tigecycline resistance in A. baumannii strains with quick adaptability. This study contributes to a better understanding of the mechanisms underlying tigecycline resistance in A. baumannii under sub-MIC pressure. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is among the most frequent microorganisms isolated from infections of burn wounds. This cross-sectional study aimed to investigate the distribution of multi-drug resistant (MDR) K. pneumoniae in two burn hospitals and the antibiotic resistance profile in different burn regions of the same patient. It was performed in two hospitals (Al-Zahraa and Al-Karama) in Al-Kut, Iraq, between January and May 2022. Totally, 100 burn swabs were collected from 40 patients of both genders suffering from burn wound infections, with ages ranging between 3 and 50 years. Klebsiella pneumoniae were isolated and identified using conventional methods followed by VITEK®2 system and confirmed via polymerase chain reaction targeting the gapA gene. Then, the antimicrobial susceptibility pattern was studied by the VITEK®2 system. Of the 100 burn wound swabs, 20 isolates were K. pneumoniae. Fifty five percent (11 out of 20) of K. pneumoniae isolated in the current study were MDR and 35% of the isolates had the extended spectrum beta-lactamase (ESBL) which is the main antibiotic resistance mechanism. Furthermore, the bacteria isolated from different burned areas of the same patient showed variable pattern of antibiotic susceptibility. To conclude, K. pneumoniae contaminating the burn wards in the Iraqi hospitals are mostly MDR, against which tigecycline is the most effective antibiotic. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter species are aerobic gram-negative bacteria that are ubiquitous in nature. Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. We aimed this study to evaluate resistance pattern of a threatening pathogen i.e., Acinetobacter baumannii. Materials and method: The present study was conducted in Microbiology Department of SBKSMIRC, Dhiraj Hospital, Waghodia, Gujarat during May 2022 to December 2022. This study included all Acinetobacter baumannii isolated from all ages and microbiological specimens which were referred to Central Microbiology Laboratory of Dhiraj Hospital. The Non-Lactose fermenting, oxidase negative organisms are kept in VITEK 2 automated system for identification and sensitivity. All isolates identified as Acinetobacter baumannii were included in the study. Results: This study included a total of 52 isolates of A.baumannii. Out of which 33% were respiratory samples (sputum, Endo-tracheal secretions), 33% were pus samples, 11% were urine samples and 23% were included in other (blood, CSF, Body fluids). The most resistant drug was ceftriaxone (88.46%). Tigecycline was found to be 100% sensitive. Conclusion: This study concludes that Tigecycline is the only drug which is most sensitive for A. baumannii and other higher drugs such as Polymixin B, Colistin etc. shows less resistance. Acinetobacter infection would remain a therapeutic challenge in our hospital and health care settings due to the increasing rate of Acinetobacter species with traits of MDR and resistance to high potent antimicrobial agents. [ABSTRACT FROM AUTHOR]

Objective: To establish a high-performance liquid chromatography–tandem mass spectrometry method (HPLC–MS/MS) to simultaneously determine colistin sulfate and tigecycline in human plasma. Methods: Polymyxin B1 internal standard (20 µL) was added into 200 µL of plasma sample. The samples were treated with methanol-5% trichloroacetic acid (50:50, V/V) solution, and the protein precipitation method was adopted for post-injection analysis. The chromatographic column was a Dikma C18 (4.6 mm × 150 mm, 5 μm). For the mobile phase, 0.1% formic acid in aqueous solution was used for phase A, 0.1% formic acid in acetonitrile solution for phase B, and gradient elution was also applied. The flow rate was 0.8 mL/min, the column temperature was 40 °C, and the injection volume was 10 µL; Electrospray ionization and multiple reaction ion monitoring were adopted and scanned by the HPLC–MS/MS positive ion mode. Results: The endogenous impurities in the plasma had no interference in the determination of the analytes. There existed a good linear relationship of colistin sulfate within the range of 0.1–10 µg/mL (R2 = 0.9986), with the lower limit of quantification (LLOQ) of 0.1 µg/mL. There existed a good linear relationship of tigecycline within the range of 0.05–5 µg/ mL (R2 = 0.9987), with the LLOQ of 0.05 µg/mL. The intra- and inter-day relative standard deviations of colistin sulfate and tigecycline were both less than 15%, and the accuracy was between 88.21% and 108.24%. The extraction had good stability, the extraction recovery rate was 87.75–91.22%, and the matrix effect was 99.40–105.26%. Conclusion: This study successfully established a method for simultaneously detecting colistin sulfate and tigecycline plasma concentrations. The method was simple, rapid, and highly sensitive and could be applied for therapeutic medication monitoring. [ABSTRACT FROM AUTHOR]

The emergence and worldwide dissemination of mobile tigecycline resistance genes tet(X3)/tet(X4) posed an enormous threat to the public health. Urgently, feasible strategies must be implemented to restore the clinical efficacy of tetracyclines and prolong the lifespan of existing drugs to address the emerging global antimicrobial resistance threat. Herein, versatile structural scaffolds of quinones for antibiotic adjuvants discovery enlightened a promising and underappreciated reservoir to circumvent the antibiotic resistance. 2-methoxy-1,4-naphthoquinone (MNQ) exhibited the potent potentiation (4 to 32-fold) with tetracyclines, along with effective inhibition on biofilm formation. Mechanistic studies revealed that MNQ synergistically operates with tetracyclines by inhibiting the enzymatic activity of Tet(X3)/Tet(X4) proteins through interaction with their active residues. Furthermore, exposure to MNQ significantly dissipate the proton motive force, leading to a cascade of membrane structural damage and metabolic homeostasis imbalance. Encouragingly, the MNQ-tetracyclines combination showcased substantial therapeutic benefits in two in vivo infection models, as evidenced by the reduced bacterial burden and mitigated pathological injury. Our findings propose a potential therapeutic option and a novel tetracyclines' adjuvant against drug-resistant pathogens carrying Tet(X3)/Tet(X4). [ABSTRACT FROM AUTHOR]

Introduction: The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a substantial severe global public health burden. Noncarbapenemase-producing CRKP (non-CP-CRKP) is increasingly recognized as the source of severe infections. Methodology: We analyzed the genotypic, and phenotypic profiles of non-CP-CRKP strains with the whole-genome sequences isolated between 2017 and 2019 and the clinical characterization of non-CP-CRKP infection. Results: A total of 91 CRKP strains were collected, of which 5 (5.49%) strains were non-CP-CRKP. Four strains were from male patients; three strains were isolated from the bile of patients who underwent biliary interventional surgery and four had a history of antibiotic exposure. Three strains were sequence type (ST)11, one was ST1, and one was ST5523. The non-CP-CRKP strains were insusceptible to ertapenem. Three strains were susceptible to amikacin. All the strains were susceptible to imipenem, meropenem, tigecycline, ceftazidime/avibatam and polymyxin B. The ß-lactamases of non-CP-CRKP predominantly included blaCTX-M, blaSHV, and blaTEM subtypes. Two site mutations in ompK36 (p.A217S and p.N218H) and four in ompK37 (p.I70M, p.I128M, p.N230G, and m233_None234insQ) were detected accounting for carbapenem resistance. Plasmids IncFI and IncFII were found in most strains. Genes encoding aerobactin, yersiniabactin and allantoin utilization were not detected in several isolates, and all non-CP-CRKP strains did not carry rmpA gene. Conclusions: Non-CP-CRKP infected patients had a history of previous antibiotic exposure or invasive procedures. Non-CP-CRKP strains were insusceptible to ertapenem. The mechanism of resistance includes ß-lactamases production and the site mutations in ompK36 and ompK37. Several virulence genes were not detected in non-CP-CRKP. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Long‐wavelength fluorescence carbon dots (CDs) show great importance in multiple fields, especially for the biochemical sensing. Here, we proposed one type of CDs doped with nitrogen and sulfur through the hydrothermal method, which exhibited obvious yellow‐fluorescence in aqueous solution. Importantly, the fluorescence intensity of CDs decreased with pH decreasing in the acidic range, thus a linear relationship between pH and fluorescence intensity was established, exhibiting the potential of pH sensing. Additionally, introducing tigecycline into CDs resulted in their decreased fluorescence, thus, we further established a strategy of detecting tigecycline with the concentration range of 200 μM to 7 nM. Meanwhile, we elucidated the static quenching as the major mechanism for CDs responding tigecycline, which was induced by the formed new complex between CDs and tigecycline. Furthermore, the practicality of the method was verified by examining the recovery of tigecycline in the actual lake‐water samples. [ABSTRACT FROM AUTHOR]

The identification of targets whose inactivation increases the activity of antibiotics helps to fight antibiotic resistance. Previous work showed that a transposon-insertion mutant in the gene PA14_27940 increases Pseudomonas aeruginosa susceptibility to aminoglycosides. Since polar effects may affect the phenotype, in the present work, we generated an in-frame PA14_27940 deletion mutant. A PA14_27940 deletion increased the susceptibility to aminoglycosides, tetracycline, tigecycline, erythromycin and fosfomycin. Excepting fosfomycin, the other antibiotics are inducers of the MexXY efflux pump. MexXY induction is required for P. aeruginosa resistance to these antibiotics, which is post-transcriptionally regulated by the anti-repressor ArmZ. Although mexXY is inducible by tobramycin in ΔPA14_27940, the induction level is lower than in the parental PA14 strain. Additionally, armZ is induced by tobramycin in PA14 and not in ΔPA14_27940, supporting that ΔPA14_27940 presents an ArmZ-mediated defect in mexXY induction. For its part, hypersusceptibility to fosfomycin may be due to a reduced expression of nagZ and agmK, which encode enzymes of the peptidoglycan recycling pathway. ΔPA14_27940 also presents defects in motility, an element with relevance in P. aeruginosa's virulence. Overall, our results support that PA14_27940 is a good target for the search of adjuvants that will increase the activity of antibiotics and reduce the virulence of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in locoregional, systemic, and novel checkpoint inhibitor treatment, hepatocellular carcinoma (HCC) is still associated with poor prognosis. The feasibility of potentially curative liver resection (LR) and transplantation (LT) is limited by the underlying liver disease and a shortage of organ donors. Especially after LR, high recurrence rates present a problem and circulating tumor cells are a major cause of extrahepatic recurrence. Tigecycline, a commonly used glycylcycline antibiotic, has been shown to have antitumorigenic effects and could be used as a perioperative and adjuvant therapeutic strategy to target circulating tumor cells. We aimed to investigate the effect of tigecycline on HCC cell lines and its mechanisms of action. Methods: Huh7, HepG2, Hep3B, and immortalized hepatocytes underwent incubation with clinically relevant tigecycline concentrations, and the influence on proliferation, migration, and invasion was assessed in two- and three-dimensional in vitro assays, respectively. Bioinformatic analysis was used to identify specific targets of tigecycline. The expression of RAC1 was detected using western blot, RT-PCR and RNA sequencing. ELISA and flow cytometry were utilized to measure reactive oxygen species (ROS) generation upon tigecycline treatment and flow cytometry to detect alterations in cell cycle. Changes in mitochondrial function were detected via seahorse analysis. RNA sequencing was performed to examine involved pathways. Results: Tigecycline treatment resulted in a significant reduction of mitochondrial function with concomitantly preserved mitochondrial size, which preceded the observed decrease in HCC cell viability. The sensitivity of HCC cells to tigecycline treatment was higher than that of immortalized non-cancerous THLE-2 hepatocytes. Tigecycline inhibited both migratory and invasive properties. Tigecycline application led to an increase of detected ROS and an S-phase cell cycle arrest. Bioinformatic analysis identified RAC1 as a likely target for tigecycline and the expression of this molecule was increased in HCC cells as a result of tigecycline treatment. Conclusion: Our study provides evidence for the antiproliferative effect of tigecycline in HCC. We show for the first time that this effect, likely to be mediated by reduced mitochondrial function, is associated with increased expression of RAC1. The reported effects of tigecycline with clinically relevant and achievable doses on HCC cells lay the groundwork for a conceivable use of this agent in cancer treatment. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a highly lethal hematological malignancy in adults and children. Abnormal proliferation of leukemia stem cells (LSC) with CD34+ and CD38− phenotypes are the main clinical features of AML. Patients with AML face drug resistance and treatment failure due to a default in stem and progenitor cells. Therefore, defining LSC properties is necessary for targeting leukemia‐initiating cells. Mitochondrial mass and activity increase in AML initiating cells compared with normal stem cells. This idea has offered the inhibition of the mitochondrial translation machinery to reduce the number of leukemia‐initiating cells in patients with AML Tigecycline is an FDA‐approved microbial antibiotic that inhibits oxidative phosphorylation in mitochondria, resulting in the suppression of leukemia cell proliferation with little toxicity to normal cells. Thus, the present study was conducted to evaluate whether LSC is influenced by mitochondrial inhibition. We measured the IC50 of tigecycline in KG‐1a AML cell lines. KG‐1a AML cell lines were separated into CD34+ and CD34− cells by MACS. In the following, these cells were treated with 20 µM (IC50) tigecycline. The expression of Annexin/PI, Caspase 3, apoptotic genes (BCL2, BCLX, BAX, BAD, and P53) and proteins (P53, BAX, BCL2 and Caspase 9) was evaluated in CD34+, CD34− and KG‐1a AML cells. In addition, the telomere length and expression of hTERT were evaluated in this study. The results indicated that BCl2 (gene and protein) and BCLX gene dramatically decreased. In addition, BAD, BAX, and P53 gene and protein expression significantly increased in CD34+ AML cells compared to CD34− AML cells. The results also suggested that tigecycline induced intrinsic (Cleaved‐caspase 9/Pro‐Caspase 9 ratio) and p53‐mediated apoptosis. Furthermore, hTERT gene expression and telomere length decreased in the tigecycline‐treated groups. Taken together, our findings indicate that inhibition of mitochondrial activity with tigecycline can induce apoptosis in cancer stem cells and can be used as a novel method for cancer therapy. Significance statement: One of the main causes of treatment failure in patients with acute myeloid leukemia is the existence of cancer stem cells. Cancer stem cells have abundant mitochondria mass and high oxygen consumption compared with normal cells. Tigecycline suppresses leukemia cell proliferation by inhibiting oxidative metabolism. In this study, we have shown that the inhibition of mitochondrial activity by tigecycline affects cancer stem cells in comparison with other cells. [ABSTRACT FROM AUTHOR]

Purpose:Chryseobacterium indologenes is a clinically relevant microorganism that has been on the rise, with multidrug-resistant (MDR) strains being reported. C. indologenes carrying tet(X2) has been demonstrated to be resistant to the antibiotic tigecycline, yet, sensitive to all other members of the tetracycline family. This inconsistency in resistance prompts an inquiry into the contribution of tet(X2) to tigecycline resistance in C. indologenes. Materials and Methods: In this study, we report on a comprehensive analysis of the genomic mechanisms underlying tigecycline resistance in a MDR C. indologenes strain (CI3125) that was resistant to tigecycline but sensitive to tetracycline, doxycycline, and minocycline. We used whole-genome sequencing, quantitative reverse transcription PCR, Western blot, antibiotic-degrading tests, and efflux pump inhibiting tests to reveal the mechanism of tigecycline resistance in C. indologenes and elucidate the inconsistency in the antibiotic resistance mechanism for the tetracycline family. Results: Our findings demonstrate that CI3125 carries 60 antibiotic resistance genes distributed on 6 different genetic islands (GIs), with the potential for horizontal transfer. Notably, the tet(X2) gene is located on GI06 of CI3125. Genetic environment analysis of tet(X2) showed that all tet(X2) genes in Flavobacterium and Bacteroides share a conservative and functional ribosome-binding site upstream. Contrary to expectation, our RT-qPCR showed that tet(X2) was not transcribed in CI3125, and Western blot suggested the absence of tet(X2) protein in CI3125. Rather, we demonstrate that minimum inhibitory concentration values for tigecycline decreased two- to eight-folds in the presence of five different efflux pump inhibitors [1-(1-naphthyl- methyl)-piperazine, phenyl-arginine-β-naphthylamide, verapamil, reserpine, and carbonyl cyanide 3-chlorophenylhydrazone]. This finding provides evidence for the involvement of efflux pumps in tigecycline resistance, which is likely to be a universal mechanism among C. indologenes. Our study proposes that the inconsistency in resistance to the tetracycline family in CI3125 may be ascribed to the silence of tet(X2) and the functions of efflux pumps for tigecycline. Conclusions: Overall, our results highlight the importance of genomic approaches in understanding the underlying mechanisms of antibiotic resistance in clinically relevant microorganisms. While tet(X2) in CI3125 is silent, our findings suggest that it may be horizontally spread through GIs. Hence, our findings have significant implications for the management of C. indologenes infections in clinical settings. [ABSTRACT FROM AUTHOR]

Background: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. Methods: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. Results: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. Conclusions: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM. [ABSTRACT FROM AUTHOR]

Background: Tigecycline (TIG) is a third-generation glycylcycline derivative used as an antimicrobial and anticancer agent for the past few years. Its intricate structure makes it more vulnerable toward degradation under the influence of various environmental factors and leads to the generation of impurities. Due to its stability issues, TIG is available as a lyophilized powder for injection. The analysis of TIG becomes a cumbersome task for analysts due to its instability in solution form. As TIG works as a life-saving drug, it is important to review its analytical methods for its quality control. Objective: The present review discusses various analytical methodologies for determining TIG from its bulk, lyophilized powder, pharmacopoeial methods and factors responsible for its instability. Methods: The present review represents the analysis of data reported in the literature from 1999-2022 for the analysis of TIG. Results: Numerous alternative analytical techniques such as UV-visible spectrophotometry, spectrofluorimetric methods, RP-HPLC (reversed-phase high-performance liquid chromatography) and FT-IR (Fourier transform infrared), and electrophoresis has been reported for quantification, identification, and characterization of TIG. Conclusions: Several analytical techniques are available to be used as a quality control tool for tigecycline, including HPLC without derivatization, whereas the fluorescence technique requires derivatization using acidic dye. A few methods require tedious presample preparation techniques, become time-consuming, and involve using one or more organic solvents; there is a need to develop eco-friendlier methods for analyzing tigecycline. Highlights: Various analytical methods such as spectrometric, fluorimetric and chromatographic methods have been discussed for estimation of TIG from its bulk and different dosage form. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Suppurative otitis media is one of the most commonly encountered diseases in the otolaryngeal practice, which is well known for its multiple etiology, persistence and recurrence. Reevaluation of aerobic bacterial and fungal study to know the microbiotia in this location and also for treatment purpose antibiotic susceptibility testing using current available antibiotics of predominant bacterial pathogens were depicted in this study. Materials and Methods: In this prospective study Patients with chronic suppurative otitis media (CSOM) presenting with more than 3 weeks of ear discharge and who did not receive any topical or systemic antibiotics in the past one week were included in this study. All swabs were processed for gram stain, KOH mount, culture, biochemical reactions and sensitivity testing according to CLSI guidelines. Results: Most common organism isolated from CSOM study population was Pseudomonas aeruginosa (42.1%), followed by Staphylococcus aureus (34.2%). Most common organism isolated from CSOM study population was Pseudomonas aeruginosa (42.1%), followed by Staphylococcus aureus (34.2%). Pseudomonas aeruginosa which were isolated showed 93.7% susceptibility to amikacin, 78.1% to levofloxacin, 81.2% to Ceftazidime-clavulanic acid, 81.2% to piperacillin+tazobactum, 75% to ceftazidime, and 87.5% sensitive to meropenem. Klebsiella pneumoniae showed 75% sensitivity to amikacin and levofloxacin, 100% sensitive to meropenem, ertapenem and tigecycline. Escherichia coli and Proteus mirabilis showed 100% sensitivity to amikacin, ciprofloxacin and meropenem. S.aureus showed 84.6% susceptibility to clindamycin, 76.9% to ciprofloxacin, 84.6% to amoxicillin+clavulanic acid, 96.1% to amikacin, and all were cefoxitin sensitive. Conclusion: Microbiological testing of specimen prior to start the antibiotic therapy in CSOM patients alleviate the emergence of drug resistant of pathogens and also helps clinicians to give accurate and prompt treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Klebsiella pneumoniae is increasingly developing resistance to last-resort antibiotics such as carbapenems. This study aimed to investigate the dissemination of common carbapenemase encoding genes among 48 clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP). Materials and Methods: Antimicrobial susceptibility testing was performed by broth dilution and disc diffusion methods. The phenotypic evaluation of carbapenemase production was performed by using Modified Carbapenem Inactivation Method. Presence of carbapenemase encoding genes blaKPC, blaNDM, blaOXA-48-like, blaIMP, and blaVIM was screened by PCR. Results: Overall, carbapenemases were produced in all CRKP isolates. The blaOXA-48-like and blaNDM were the most prevalent genes detected among all and 66.6% (n=32) of CRKP isolates respectively. The blaVIM was detected in only one isolate co-harboring NDM and OXA-48-like carbapenemases. The bla KPC and blaIMP genes were not identified in any of the isolates. While tigecycline was the most active agent against CRKP isolates with low resistance rate (4.1%), high rate of resistance was observed to colistin (66.6%), amikacin (79%) and most of other tested antimicrobials. Conclusion: Our results revealed predominant prevalence of OXA-48-like and NDM carbapenemases among CRKP clinical isolates. High rate of resistance to last-resort agents such as colistin among CRKP isolates is a source of great concern. [ABSTRACT FROM AUTHOR]

The emergence and prevalence of plasmid-encoded RND-type efflux pump TMexCD-TOprJ severely compromise tigecycline treatment, which is recognized as the last resort for multidrug-resistant (MDR) Gram-negative bacterial infections. There is an urgent need for rapid antibiotic susceptibility testing (AST) that can simultaneously identify the genotype and phenotype of tmexCD-toprJ-positive bacteria. Through characterizing transcriptional profiling responses of tmexCD-toprJ-positive and -negative strains after exposure to 2 μg/mL tigecycline, here we identified 12 differentially RNA biomarkers and developed an RNA-based AST (RBAST) to distinguish tmexCD-toprJ-positive and -negative K. pneumoniae. These mRNA biomarkers were successfully validated in tigecycline exposure time variations, concentration shifts, and other tmexCD-toprJ variants. In addition, a group of clinical isolated strains was effectively distinguished using RBAST, with an accuracy of over 94% during 3 h test period. Our work highlights the potential of RNA transcripts as biomarkers for rapid AST, which will contribute to deploying effective antibiotic regimens in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: To analyse the clinical characteristics and risk factors for tigecycline‐induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non‐TIP. Methods: A retrospective case‐control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non‐TIP (pancreatitis with other causes) and non‐pancreatitis. Univariate analyses were performed to compare TIP and non‐pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP, and the safety and efficiency of tigecycline use in non‐TIP were evaluated. Results: A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non‐TIP and 3720 non‐pancreatitis. The TIP prevalence was 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non‐TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. Conclusions: The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra‐abdominal infection. [ABSTRACT FROM AUTHOR]

Background: The management and control of gonorrhea are hampered by the widespread resistance to the diverse strains of Neisseria gonorrhea. Resistance to sulfonamides, penicillins, tetracyclines, macrolides, fluoroquinolones, and early cephalosporins has emerged rapidly. Purpose: This systematic review aimed to assess what antibiotics can be used as an alternative therapy for gonorrhea infections that are resistant to antibiotics. Methods: The study was conducted using the Web of Science, PubMed, Embase, and CENTRAL databases, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Risk of Bias for Randomized Trials (RoB2) was utilized to evaluate study quality. Results: This review included 28 articles from randomized controlled trials between 2013 and 2023, distributed across five nations. The studies included 2.380 patients and clinical isolates from men and women diagnosed with gonorrhea infection at various sites. Sample testing by treatment with alternative antibiotics. Discussion: Zoliflodacin, tigecycline, and ertapenem in single or dual therapy with ceftriaxone could be considered as a potential option in treating gonorrhea resistant to antibiotics. Gentamicin cannot be recommended to replace ceftriaxone as first-line therapy. Gepotidacin is effective for the Gyr A A92T mutation in gonorrhea infection. Summary: The effectiveness of these antibiotics, zoliflodacin, ceftriaxone, gentamicin, gepotidacin, solithromycin, tigecycline, and ertapenem is considered a solution to gonorrhea resistance. Researchers should study how to provide antibiotics with intervening multidrug efflux pumps to overcome gonococcal antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to establish the in vitro efficacy and susceptibility profiles of new β-lactam antibiotics against clinically isolated carbapenemase-producing Klebsiella pneumoniae (CPKP) strains. Materials and Methods: A total of 117 nonduplicated CPKP isolates were tested against cefiderocol, cefepime-zidebactam, ceftazidime-avibactam, tigecycline, and other 20 antibiotics by broth microdilution. The carbapenemase genes were identified using PCR and sequencing, while multilocus sequence typing established the bacterial strains. Results: Three significant sequence types (STs), including ST147, ST16, and ST11, were shown to be the dominant STs, which occupied ∼90% of the tested population. Three carbapenemase genes, blaNDM-1, blaOXA-181, and blaOXA-232, were detected. The blaNDM-1 was found in ST147 and ST16 but not in ST11, while the blaOXA-232 was not detected in ST147. The majority of ST16 isolates contained both blaNDM-1 and blaOXA-232, which was not seen in other strains. Cefiderocol, cefepime-zidebactam, and tigecycline were the most active agents against CPKP. Both MIC50 and MIC90 of these three antibiotics remained within the susceptible categories, while nearly all other antibiotics were in the resistant levels. However, in ST11, which carried only blaOXA genes without blaNDM-1, ceftazidime-avibactam was effective with the MIC90 at 2 μg/mL. In addition, amikacin was shown to have good activity in ST11. In contrast, gentamicin was active in only ST16 and ST147. Conclusions: This study is the first report that demonstrates the prevalence of CPKP, distribution of strains, resistant genes, and antimicrobial susceptibility profiles in northern Thailand. These data would contribute to appropriate individual treatment and the selection of infection control strategies. [ABSTRACT FROM AUTHOR]