Clinical Efficacy and Safety Analysis of Tigecycline in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Combined with Multidrug-Resistant Acinetobacter baumannii Infection

Objective:To study the clinical efficacy and safety of tigecycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD)combined with multidrug-resistant Acinetobacter baumannii infection.Methods:113 patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection were recruited between January 2021 and January 2023,and given tigecycline treatment.The total effective rate,lung function indexes,related biochemical index levels,and the incidence rate of adverse reactions were observed after the treatment.Results:After the treatment,100 patients were cured,1 case with apparent effect,2 cases were effective,10 cases were ineffective,and the total effective rate was 91.15%.The post-treatment CRP(21.22±3.35 mg/L),PCT(3.18±1.11 ng/L),CRE(76.36±9.24μmol/L),and ALT(37.76±6.99 U/L)were significantly improved as compared to the pre-treatment(P<0.05).After treatment,10 cases of vomiting(8.85%),13 cases of nausea(11.50%),4 cases of diarrhea(3.53%),1 case of abdominal pain(0.88%),and 2 cases of allergy(1.77%)were observed in 113 patients.Conclusion:Tigecycline therapy for patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection not only has significant therapeutic efficacy but also has a high degree of safety.

Sequential intraventricular injection of tigecycline and polymyxin B in the treatment of intracranial Acinetobacter baumannii infection after trauma: a case report and review of the literature

Background:Intracranial infection after craniotomy is one of the most serious postoperative complications,especially multidrug-resistant(MDR)or extensively drug-resistant(XDR)bacterial meningitis,and strongly affects the prognosis of patients.Current treatment experience regarding these infections is scarce.Case presentation:We report a case of severe intracranial infection of XDR Acinetobacter baumannii(A.baumannii)that was treated by intravenous(IV)injection,sequential intraventricular(IVT)injection of tigecycline and polymyxin B,and other anti-infective drugs.Good results were obtained,and the patient was eventually discharged from the hospital.This case is characterized by intracranial infection.Conclusions:The polymyxin B IV+IVT pathway is an ideal treatment strategy for XDR A.baumannii.The tigecycline IVT pathway is also a safe treatment option.

Successful treatment of pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii with multi-route tigecycline: A case report

BACKGROUND Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii(A.baumannii)is one of the most severe complications associated with craniotomy.However,limited therapeutic options exist for the treatment of A.baumannii ventriculitis due to the poor penetration rate of most antibiotics through the blood-brain barrier.CASE SUMMARY A 68-year-old male patient with severe traumatic brain injury developed pyogenic ventriculitis on postoperative day 24 caused by extensively drug-resistant A.baumannii susceptible to tigecycline only.Successful treatment was accomplished through multi-route administration of tigecycline,including intravenous combined with continuous ventricular irrigation plus intraventricular administration.The pus was cleared on the 3rd day post-irrigation,and cerebrospinal fluid cultures were negative after 12 d.CONCLUSION Our findings suggest that multi-route administration of tigecycline can be a therapeutic option against pyogenic ventriculitis caused by extensively drugresistant A.baumannii.

Treatment of Donor-derived Carbapenem-resistant Klebsiella pneumoniae Infection after Renal Transplantation with Tigecycline and Extended-infusion Meropenem

Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,monotherapy with this drug is often less than effective.We investigated the efficacy of a combined regimen of tigecycline with high-dose,extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.Methods From Jan.2016 to Dec.2017,a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute.Probable or possible donor-derived infection(DDI)was identified in 8 transplant recipients.Clinical data were retrospectively analyzed.Results Klebsiella pneumoniae carbapenemase-2(KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation,leading to surgical site(n=3),urinary tract(n=4),and/or bloodstream(n=2)infections in 8 recipients.The drug susceptibility tests showed that CRKP was sensitive to tigecycline,but resistant to meropenem.In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem,DDIs were successfully cured.The length of hospital stay was 31(18–129)days,and the serum creatinine at discharge was 105.8±16.7µmol/L.The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock.A median follow-up of 43 months(33–55)showed no recurrence of new CRKP infection in the 7 surviving recipients.Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

Tigecycline sclerotherapy for recurrent pseudotumor in aseptic lymphocyte-dominant vasculitis-associated lesion after metal-onmetal total hip arthroplasty:A case report

BACKGROUND Metal-on-metal(MoM)total hip arthroplasty(THA)has been associated with adverse reactions to metal debris,presenting clinically as pseudotumors.CASE SUMMARY This case report presents a female aged 73 year-old with MoM THA-related pseudotumor.After arthrotomy and bursectomy surgeries,histologic examinations of surgical specimens revealed a specific lymphocyte-dominant immunologic response,now known as aseptic lymphocyte-dominant vasculitisassociated lesion(ALVAL).Due to soft tissue persisting effusion after arthrotomy and bursectomy,revision surgery was then performed with ceramic-onpolyethylene THA.However,revision did not resolve the patient’s symptoms.Here we describe our application of tigecycline sclerotherapy to treat recurrent pseudotumor after revision THA and no recurrence after 24-mo follow-up.CONCLUSION Tigecycline sclerotherapy is safe and effective in the management of recurrent pseudotumor after revision non-MoM THA in ALVAL cases.

Tigecycline Use in Surgical Intensive Care Unit for the Treatment of Complicated Intra-Abdominal Infections: A Real-World Study

OBJECTIVES: To describe real-world use of tigecycline in cIAIs patients. METHODS: A retrospective, observational study enrolled cIAIs patients hospitalized in The First Affiliated Hospital, Sun Yat-sen University from January 1, 2013 to June 30, 2017 was conducted. Patients’ data were collected and matched based on age, gender, and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score according to receiving first-line, later-line, or no tigecycline during hospitalization. RESULTS: Data were collected for 52 patients. 82.6% were male. Mean age was 57.8 years and APACHE II score was 14.8. The incidence of both extended-spectrum beta-lactamase producing and carbapenem-resistant pathogens was high on initial culture;however, few patients received first-line tigecycline. No significant difference in mortality rate was identified among first-line, later-line and no tigecycline users. Of surviving patients, shorter hospital length of stay was observed for patients receiving first- vs later-line or no tigecycline, respectively. ICU length-of-stay was shorter in patients receiving first- vs later-line or no tigecycline. CONCLUSIONS: First-line tigecycline use was rare in our surgical intensive care unit. Resistant organisms were commonly cultured from initial specimens. Although these results are limited by small patient numbers and single center, our results suggest that early tigecycline use may have significant benefits with similar mortality. Further research is warranted to demonstrate the values of early tigecycline use in cIAIs patients.

Mechanisms of tigecycline resistance in Gram-negative bacteria:A narrative review

Tigecycline serves as a critical“final-resort”antibiotic for treating bacterial infections caused by multidrug-resistant bacteria for which treatment options are severely limited.The increasing prevalence of tigecycline resistance,particularly among Gram-negative bacteria,is a major concern.Various mechanisms have been iden-tified as contributors to tigecycline resistance,including upregulation of nonspecific Resistance Nodulation Divi-sion(RND)efflux pumps due to mutations in transcriptional regulators,enzymatic modification of tigecycline by monooxygenase enzymes,and mutations affecting tigecycline binding sites.This review aims to consolidate our understanding of tigecycline resistance mechanisms in Gram-negative bacteria and offer insights and perspectives for further drug development.

Emergence of plasmid-mediated tigecycline resistance tet(X4)gene in Enterobacterales isolated from wild animals in captivity

Background Over the past few decades,antimicrobial resistance(AMR)has emerged as a global health challenge in human and veterinary medicine.Research on AMR genes in captive wild animals has increased.However,the presence and molecular characteristics of tet(X)-carrying bacteria in these animals remain unknown.Methods Eighty-four samples were collected from captive wild animals.tet(X)variants were detected using polymerase chain reaction and the isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.All isolated strains were subjected to antimicrobial susceptibility testing and whole-genome sequencing.The virulence of an Escherichia coli strain carrying enterotoxin genes was assessed using a Galleria mellonella larval model.Results We isolated two tet(X4)-positive E.coli strains and one tet(X4)-positive Raoultella ornithinolytica strain.Antimicrobial susceptibility tests revealed that all three tet(X4)-carrying bacteria were sensitive to the 13 tested antimicrobial agents,but exhibited resistance to tigecycline.Notably,one tet(X4)-carrying E.coli strain producing an enterotoxin had a toxic effect on G.mellonella larvae.Whole-genome sequencing analysis showed that the two tet(X4)-carrying E.coli strains had more than 95%similarity to tet(X4)-containing E.coli strains isolated from pigs and humans in China.Conclusion The genetic environment of tet(X4)closely resembled that of the plasmid described in previous studies.Our study identified tet(X4)-positive strains in wildlife and provided valuable epidemiological data for monitoring drug resistance.The identification of enterotoxin-producing E.coli strains also highlights the potential risks posed by virulence genes.

Yellow-Fluorescence Carbon Dots Employed for pH Sensing and Detection of Tigecycline

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.

RNA-based antibiotic susceptibility testing of tmexCD-toprJ-mediated tigecycline resistance in Klebsiella pneumoniae

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 2μg/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.

Antimicrobial susceptibility of vancomycin-resistant staphylococci of clinical origin in Bareilly, North India

Background:Vancomycin resistance(VR)in staphylococci is emerging fast and posing serious health problems as vancomycin is considered the drug of choice for the treatment of methicillin-resistant staphylococcal infections.Much research has been done on vancomycin-resistant Staphylococcus aureus(VRSA)strains infecting humans and animals but little is understood about other vancomycin-resistant staphylococci(VRS).This study was conducted to determine diversity among staphylococcal species causing infections and to know effective antimicrobials for therapeutic intervention for treatment of infections with vancomycin resistant staphylococci.Methods:Antimicrobial susceptibility data of 620 strains of staphylococci isolated from January 2016 to December 2023 from referred clinical samples were retrieved with their host of origin and association with different types of infections in animals,birds and humans from Clinical Epidemiology of the Institute.All isolates were tested for VR through their growing ability on vancomycin-supplemented(6µg mL-1)brain heart infusion agar.Data was analysed in Microsoft Excel.Results:Staphylococci strains(620)belonged to 26 species and 287 vancomycin-resistant.Of the 287 VRS strains detected only 46(16.03%)were VRSA.Irrespective of their origin and association with different ailments VRS strains were more resistant to herbal and conventional antimicrobial than VSS strains.The most effective antibiotics inhibiting≥80%of the staphylococci were tigecycline,imipenem,nitrofurantoin,linezolid and chloramphenicol inhibiting 88%,86%,86%,81%and 81%of the MRS and 92.31%,94.88%,92.25%,89.09%and 86.56%VRS strains,respectively.Among herbal antimicrobials,the most effective herbal compound was carvacrol followed by thyme oil,cinnamledehyde and ajowan oil,inhibiting≥80%of the strains.VR was most common among S.xylosus,S.schleiferi,and S.delphini strains while S.caseolyticus strains had the least probability of having VR.Staphylococci from mastitis cases had the least probability of possessing VR while those from wound infection had the highest probability of having VR.Conclusion:The study revealed that besides S.aureus,25 more species of staphylococci may be infecting animals,birds and humans.VR was more common in S.xylosus,S.schleiferi,S.auricularis,S.delphini and S.hyicus than in S.aureus strains,and of the VRS and MRS strains,83.97%and 83.46%were non-VRSA and non-methicillin-resistant S.aureus,respectively.Imipenem,tigecycline,nitrofurantoin,chloramphenicol,linezolid,meropenem and minocycline may be a better choice for the treatment of infections caused by methicillin as well as vancomycin-resistant staphylococci.

A novel antibacterial biomaterial mesh coated by chitosan and tigecycline for pelvic floor repair and its biological performance

The biomaterials composed of mammalian extracellular matrix(ECM)have a great potential in pelvic floor tissue repair and functional reconstruction.However,bacterial infection does cause great damage to the repair function of biomaterials which is the major problem in clinical utilization.Therefore,the development of biological materials with antimicrobial effect is of great clinical significance for pelvic floor repair.Chitosan/tigecycline(CS/TGC)antibacterial biofilm was prepared by coating CS/TGC nanoparticles on mammalian-derived ECM.Infrared spectroscopy,scanning electron microscopy,bacteriostasis circle assay and static dialysis methods were used to characterize the membrane.MTS assay kit and DAPI fluorescence staining were used to evaluate cytotoxicity and cell adhesion.The biocompatibility was assessed by subabdominal implantation model in goats.Subcutaneous antimicrobial test in rabbit back was used to evaluate the antimicrobial and repairing effects on the infected wounds in vivo.Infrared spectroscopy showed that the composite coating had been successfully modified.The antibacterial membrane retained the main structure of ECM multilayer fibers.In vitro release of biomaterials showed sustained release and stability.In vivo studies showed that the antibacterial biological membrane had low cytotoxicity,fast degradation,good compatibility,anti-infection and excellent repair ability.

Detection of Plasmid-Mediated Tigecycline Resistance Gene tet(X4) in a Salmonella enterica Serovar Llandoff Isolate

The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank.The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays.The genetic features of the tet(X4)-bearing plasmid sequence were analyzed.Here,we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4)in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606,isolated from a man in China in 2016,the first reported serovar Llandoff in China as a novel sequence type ST8300.The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53,resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline.The tet(X4)gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4.To our knowledge,this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4)in a Salmonella Llandoff strain isolated from a human stool sample in China.In addition,our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents,posing a serious threat to humans and public health.Overall,our timely discovery of the recent emergence of the tet(X4)gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.

Tigecycline resistance tet(X3)gene is going wild

The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.While tet(X4)was not identified in our samples,tet(X3)was found in two gut microbiomes of bird fecal samples,with 100%amino acid identity of sites 150–387.These results suggest that tet(X3)has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.

Stenotrophomonas maltophilia,an emerging pathogen in newborns:Three case reports and a review of the literature

BACKGROUND Stenotrophomonas maltophilia(S.maltophilia)is a rare cause of neonatal sepsis with significant morbidity and mortality and has extensive resistance to several antibiotics leaving few options for antimicrobial therapy.Only a few cases have been reported in neonates from developing countries.We report three cases of critically ill,extramural babies with neonatal S.maltophilia sepsis.All three babies recovered and were discharged.CASE SUMMARY All three cases were term extramural babies,who were critically ill at the time of presentation at our neonatal intensive care unit.They had features of multiorgan dysfunction at admission.Blood culture was positive for S.maltophilia in two babies and one had a positive tracheal aspirate culture.The babies were treated according to the antibiogram available.They recovered and were subsequently discharged.CONCLUSION Although various authors have reported S.maltophilia in pediatric and adult populations,only a few cases have been reported in the newborn period and this infection is even rarer in developing countries.Although S.maltophilia infection has a grave outcome,our three babies were successfully treated and subsequently discharged.

Efficacy and Safety of Three Anti-infective Therapeutic Regimens for the Multidrug-resistant Acinetobacter Baumannii Infection:ASystematic Review and Meta-analysis

Background: Due to extensive use of antibiotics, multidrug resistance of Acinetobacter baumannii (A.b) infection has become one of the major challenges in clinic, which is difficult to treat and have a high mortality rate. Based on this, we must take pro active measures against antimicrobial resistance by improving the efficacy. To provide a high-quality clinical evidence, a meta-analysis was conducted to compare the efficacy and safety of three anti-infection therapeutic regimens for the treatment of multidrug resistance of Acinetobacter baumannii(MRAB) infection. Methods: A meta-analysis of 36 randomized controlled trials, comprising approximately 3014 patients, was conducted to compare the efficacy and safety of three anti-infection therapeutic regimens for the treatment of MRAB infection. The clinical response rate and microbiological response rate between cefbperazone-sulbactam group and tigecycline plus cefbperazone-sulbactam group were RR=1.33, 95% CI= 1.27-1.39 and RR=1.72, 95% CI=1.55-1.90, respectively;Cefoperazone-sulbactam group and tigecycline plus isepamicin group were RR=1.29, 95% CI=1.19-1.39 and RR=1.59, 95% CI=1.37-1.84, respectively. Results: There was no significant difference between tigecycline plus cefbperazone-sulbactam group and tigecycline plus isepamicin group in the clinical response rate or microbiological response rate. Neither was there any adverse events (AEs) among the three regimens. Conclusion: Our finding suggested that tigecycline combined with cefbperazone-sulbactam or isepamicin may be performed with more efficacy than cefoperazone-sulbactam monotherapy in MRAB infections treatment.

Analysis of infection and prognosis of extensively drug resistant Acinetobacter baumannii in ICU

Objective:To investigate the infection of patients in the ICU with extensively drug-resistant Acinetobacter baumannii(XDRAB)and analyse the effect of tigecycline therapy for XDRAB.Methods:Seventy-one patients admitted to the ICU with XDRAB infection from January 2013 to July 2017 were divided into the tigecycline group(combination therapy with 50 mg tigecycline and 0.1 g minocycline every 12 hours)or the control group(no tigecycline treatment).Patient data,including age,sex,history of malignant tumour,body temperature,APACHE Ⅱ score,ALT,AST,GGT,TB,ALB,TBIL,DBIL,IBIL,BUN,Cr,absolute neutrophil count,procalcitonin(PCT),site positive for XDRAB infection,length of stay,and prognosis,were collected and compared between the two groups.Binary logistic regression was used to analyse the prognostic risk factors for XDRAB.Results:A total of 61.6% of the patients infected with XDRAB had multiple sites of XDRAB colonization.The cure rate achieved in the tigecycline group was higher than that of the control group(70.7%vs 41.9%).Multivariate analysis showed that older age,a high level of PCT after treatment and the absence of tigecycline treatment were poor prognostic factors for XDRAB infection.Conclusion:Combination therapy with tigecycline and minocycline is effective for XDRAB infection and reduces the cost of treatment.Combined therapy with tigecycline is a predictor of good prognosis for patients infected with XDRAB,whereas older age and increased PCT levels after treatment are predictors of poor prognosis.

Epidemiology and genetic characterization of tet(X4)-positive Klebsiella pneumoniae and Klebsiella quasipneumoniae isolated from raw meat in Chengdu City, China

The rapid spread of mobile tigecycline resistance presents a significant public health threat,particularly with the increasing prevalence of tet(X4)-positive Enterobacterales across various species.This study aimed to inves-tigate the epidemic features and transmission dynamics of tet(X4)-positive Klebsiella pneumoniae(K.pneumo-niae)through the analysis of 206 raw meats,including pork(n=182),beef(n=16),duck(n=5),and chicken(n=3).These samples were collected from schools,markets,and restaurants in Chengdu City,China.A total of 25 isolates were obtained from 13 administrative regions.All isolates exhibited resistance to tetracycline,tigecycline,ampicillin,chloramphenicol,and florfenicol.Over half of the isolates also demon-strated resistance to streptomycin(80%),sulfamethoxazole/trimethoprim(72%),ciprofloxacin(64%),and ampicillin/sulbactam(56%).Among these strains,14 distinct sequence types(STs)were identified,revealing evidence of inter-regional clonal spread,notably among 9 K.pneumoniae ST3393.Phylogenetic analysis revealed the presence of two K.pneumoniae ST5 closely resembling hypervirulent K.pneumoniae from Jiangsu.Importantly,12 isolates were capable of transferring tigecycline resistance to Escherichia coli J53.Further plasmid analysis showed that the tet(X4)-harboring plasmids in K.pneumoniae could be classified into four types,primarily belonging to the IncFIA(HI1)/HI1A/HI1B hybrid plasmid(n=16)and IncFII plasmid(n=7),which significantly contributed to the cross-species dissemination of tet(X4).In summary,this study highlights the prevalence of MDR tet(X4)-positive K.pneumoniae in Chengdu,driven predominantly by clonal expansion and plasmid-mediated horizontal gene transfer.These findings emphasize the importance of contin-uous surveillance of tet(X4)-positive K.pneumoniae in raw meat and the implementation of effective measures to control their spread.