Use Of Tigecycline Research Articles

Effective strategies for managing trimethoprim-sulfamethoxazole and levofloxacin-resistant Stenotrophomonas maltophilia infections: bridging the gap between scientific evidence and clinical practice.

To discuss the therapeutic options available for the management of difficult-to-treat strains of Stenotrophomonas maltophilia (Sma), namely those resistant to trimethoprim-sulfamethoxazole and fluoroquinolones. Recent pharmacological studies have highlighted the fact that current breakpoints for first-line antibiotics against Sma are too high. In light of these data, it is likely that the prevalence of difficult-to-treat (DTR) Sma is underestimated worldwide. Two promising alternatives for treating DTR strains are cefiderocol and the combination of aztreonam and an L2 inhibitor. However, clinical trials are currently very limited for these antibiotics and no comparative studies have been carried out to date. It is important to note that the clinical efficacy of cefiderocol appears to be inferior to that initially anticipated from in-vitro and animal studies. Consequently, minocycline and ceftazidime may remain viable options if they are used against strains with a low minimum inhibitory concentration. We advise against the use of intravenous polymyxins and tigecycline. Finally, recent literature does not support the systematic use of combination therapy or long-course treatments. In the coming years, phage therapy may become a promising approach against DTR Sma infections. Overall, clinical comparative studies focused on DTR strains are required in order to provide more accurate and actionable information for therapeutic decisions.

Risk factors for bloodstream infection among patients admitted to an intensive care unit of a tertiary hospital of Shanghai, China

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.

Tigecycline as Salvage Therapy in a Neonate with Multidrug-resistant Klebsiella pneumoniae Meningitis and Ventriculitis – Case Report and Literature Review

Multi drug resistant (MDR) infections especially in paediatric population, with already limited treatment options, often leave clinicians at loss for an effective antimicrobial treatment making us as helpless as in pre-antibiotic era. Tigecycline is an ‘immature’ antibiotic for children. According to FDA, tigecycline is only indicated in patients 18 years of age and older for the treatment of complicated MDR infection. According to the published literature, the youngest patient on whom Tigecycline treatment has been attempted was 73 day old baby born at 27 weeks gestation with a birth weight of 1028 grams having Acinetobacter baumanii ventriculitis . Here, we discuss use of Tigecycline in a neonate with MDR Klebsiella Pneumoniae meningitis and ventriculitis who presented to us on day 12 of life. Child was born preterm at 34 weeks and 3 days by Lower Segment Caesarean Section in view of foetal distress, maternal preeclampsia and gestational hypothyroidism in a private hospital. On 12thday of life the baby presented to our hospital after being referred with complaints of abnormal body movements, lethargy, difficulty in taking feeds and difficulty in breathing. The complaints had been documented to be present since birth but were increasing over time. Aerobic culture of CSF led to isolation of multi-drug resistant (MDR) Klebsiella pneumoniae resistant to most empirical antibiotics, with intermediate susceptibility to Amikacin susceptibility to Colistin and Tigecycline. We found our isolate produced both NDM and OXA-48 contributing to the increased virulence and resistance of the strain. Considering the paucity of knowledge of Tigecycline’s efficacy and safety in children less than 8 years, lack of FDA approval and the fact that CSF bioavailability is considered low, Tigecycline therapy was deferred and infant was continued on injection Meropenem and injection Amikacin. Condition of child did not improve and marginal weight gain was documented over next 10 days. CSF culture from repeat LP again grew Klebsiella pneumoniae with same susceptibility pattern. On day 23 due adverse affects, and injection Tigecycline was added. A total of 42 days of Meropenem and 21 days of Tigecycline were completed and child was discharged after 42 days of hospital stay. Child was gaining weight, taking feeds orally and no abnormal body movements were present. The child is being followed up for long term sequelae of HIE 2 and meningitis on OPD basis

Tigecycline-associated hypofibrinogenemia: A single center, retrospective, controlled study

BackgroundTigecycline-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. MethodsThe 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. ResultsThe 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). ConclusionHypofibrinogenemia 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.

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Abstract 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.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study

ObjectiveThis study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE.MethodsThis was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis.ResultsThis study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups.ConclusionsThe detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Clinical use of tigecycline may contribute to the widespread dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae strains

ABSTRACT The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses grave threats to human health. These strains increased dramatically in clinical settings in China in the past few years but not in other parts of the world. Four isogenic K. pneumoniae strains, including classical K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP) and CR-hvKP, were created and subjected to phenotypic characterization, competition assays, mouse sepsis model and rat colonization tests to investigate the mechanisms underlying the widespread nature of CR-hvKP in China. Acquisition of virulence plasmid led to reduced fitness and abolishment of colonization in the gastrointestinal tract, which may explain why hvKP is not clinically prevalent after its emergence for a long time. However, tigecycline treatment facilitated the colonization of hvKP and CR-hvKP and reduced the population of Lactobacillus spp. in animal gut microbiome. Feeding with Lactobacillus spp. could significantly reduce the colonization of hvKP and CR-hvKP in the animal gastrointestinal tract. Our data implied that the clinical use of tigecycline to treat carbapenem-resistant K. pneumoniae infections facilitated the high spread of CR-hvKP in clinical settings in China and demonstrated that Lactobacillus spp. was a potential candidate for anticolonization strategy against CR-hvKP.

Predictors of Mortality, Drug Resistance, and Determinants among Carbapenem‐Resistant Enterobacteriales Infections in Chinese Elderly Patients

Elderly patients with carbapenem‐resistant Enterobacteriales (CRE) infections represent considerable mortality rates. But data on the risk factors for the death of elderly patients following such infection remain limited. We aimed to assess the clinical outcomes, identify mortality‐associated risk factors, and determine the antibiotic resistance and resistance genes of isolates for these patients. Hospitalized patients aged ≥65 years with CRE infection from January 2020 to December 2020 were retrospectively reviewed. Isolates identification and molecular characterization of CRE were carried out. Logistic regression analysis was applied to assess the potential factors associated with mortality. Of the 123 elderly patients with CRE infection included in our study, the all‐cause mortality rate was 39.8% (49/123). The most prevalent pathogen was carbapenem‐resistant Klebsiella pneumoniae (CRKP, 116 of 123). The overall rates of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) were 100.0% and 66.7%. All CRE isolates exclusively harbored a singular variant of carbapenemase gene, such as blaKPC−2, blaIMP−4, blaNDM−5, or blaOXA−48, while 98.4% of isolates harbored more than one β‐lactamase gene, of which 106 (86.2%) isolates harbored blaCTX−M, 121 (98.4%) isolates harbored blaTEM, and 116 (94.3%) isolates harbored blaSHV. Multivariable logistic regression analysis revealed that mechanical ventilation (adjusted odds ratio (AOR) = 33.607, 95% confidence interval (CI): 4.176‐270.463, P &lt; 0.001), use of tigecycline during hospitalization (AOR = 5.868, 95% CI: 1.318‐26.130, P = 0.020), and APACHE II score (AOR = 1.305, 95% CI: 1.161–1.468, P &lt; 0.001) were independent factors associated with increasing the mortality of patients with CRE infection, while admission to intensive care unit (ICU) during hospitalization (AOR = 0.046, 95% CI: 0.004–0.496, P = 0.011) was a protective factor. CRE‐infected elderly patients with mechanical ventilation, use of tigecycline during hospitalization, and high APACHE II score were related to poor outcomes. The isolates carried various antibiotic genes and presented high antibiotic resistance. These findings provide crucial guidance for clinicians to devise appropriate strategies for treatment.

Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections.

Tigecycline (TIG) is a broad-spectrum antibiotic that has been approved for the treatment of a number of complicated infections, including community-acquired bacterial pneumonia. Currently it is available only as an intravenous injection that undergoes rapid chemical degradation and limits the use to in-patient scenarios. The use of TIG as an inhaled dry powder inhaler may offer a promising treatment option for patients with multidrug-resistant respiratory tract infections, such as Stenotrophomonas maltophilia (S. maltophilia). This study explores the feasibility of engineering an inhaled powder formulation of TIG that could administer relevant doses at a wide range of inhalation flow rates while maintaining stability of this labile drug. Using air-jet milling, micronized TIG had excellent aerosolization efficiency, with over 80% of the device emitted dose being within the respirable range. TIG was also readily dispersed using different inhaler devices even when tested at different pressure drops and flow rates. Additionally, micronized TIG was stable for 6 months at 25 °C/60% RH and 40 °C/75% RH. Micronized TIG maintained a low minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of 0.8 μM and >0.5 μM, respectively in S. maltophilia cultures in vitro. These results strongly suggest that the micronization of TIG results in a stable and respirable formulation that can be delivered via the pulmonary route for the treatment of lung infections.

Effect of a national antibiotic stewardship intervention in China targeting carbapenem overuse: An interrupted time-series analysis

To assess trends and patterns of carbapenem use and to evaluate the effects of a nationwide antibiotic stewardship policy to reduce carbapenem overuse. In this quasi-experimental study, using longitudinal data from the national drug procurement database and interrupted time-series analyses with carbapenems as the intervention group and possible carbapenem substitutes as the comparison group, we evaluated the effects of a national stewardship policy on carbapenem consumption and expenditures, by region and types of healthcare institutions. The carbapenem procurement volume declined by -28.8% (95% CI -35.0 to -22.6) (-334.4 thousand defined daily doses [DDDs] per month), and carbapenem expenditures showed a relative reduction of -38.1% (-43.9 to -32.2). The gap between the use of carbapenems and each drug in the comparison group narrowed after the policy intervention, with an increase in tigecycline use (14.9 thousand DDDs [10.8-18.9]) and a slower decrease in use of certain third-generation cephalosporin combinations (-85.7 [-143.0 to -28.4]), penicillin combinations (-200.9 [-421.4-19.6]), and fourth-generation cephalosporins (-116.9 [-219.8 to -14.0]). Consumption was highest during the pre-policy period, and declines were largest following the intervention in the eastern region (-32.1%, -39.8 to -24.4) and among tertiary hospitals (-266.2 [-339.5 to -192.9] thousand DDDs per month). This population-level drug utilization research represents the first comprehensive evaluation of the effectiveness of China's nationwide carbapenem stewardship. The national policy targeting carbapenem prescribing has led to a sustained reduction in carbapenem use with limited substitution. Effects varied geographically and were concentrated in tertiary and secondary hospitals.

Rational use of tigecycline and tigecycline blood concentration monitoring in patients with severe infection.

Tigecycline, a tetracycline antibiotic, is widely used against antimicrobial resistance; therefore, medical staff should use tigecycline rationally to improve clinical efficacy and reduce resistance to this drug. The present study aimed to enhance the rate of rational tigecycline usage. The patients were divided into a low-dose (50 mg tigecycline twice daily, every 12 h) and a high-dose group (100 mg twice daily, every 12 h). The blood concentrations of tigecycline were examined and the area under the curve (AUC)0-12 h values of the two groups were calculated. Prescriptions of tigecycline for 40 intensive care unit (ICU) cases were reviewed to evaluate the rationality of tigecycline usage. The peak plasma concentrations (the 7th administration after 1 h) of tigecycline were significantly higher in the high-dose group (2.46±0.43 µg/ml) compared with those in the low-dose group (1.25±0.16 µg/ml). The AUC0-12 h was 16.35±3.09 h µg/ml in the high-dose group and 9.83±1.23 h µg/ml in the low-dose group (P<0.001). There were 29 irrational prescriptions identified, involving: i) Lack of consultation records (n=20); ii) inappropriate usage or dosage (n=17); iii) inappropriate drug selection (n=2); or iv) lack of dynamic laboratory tests to evaluate the efficacy (n=4). The irrational use of tigecycline in ICU patients is common. The rate of rational tigecycline usage can be improved by strengthening the management, training and participation of clinical pharmacists.

Clinical characteristics of carbapenem-resistant Klebsiella pneumoniae infection/colonisation in the intensive care unit: a 9-year retrospective study

ObjectivesCarbapenem-resistant Klebsiella pneumoniae (CRKP) infection/colonisation has been reported in hospitals. The clinical characteristics of CRKP infection/colonisation in the intensive care unit (ICU) have received little attention. This study aims to...

Clinical characteristics and risk factors for tigecycline-induced pancreatitis in a tertiary hospital: a retrospective study.

To analyze the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. 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. 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 prevalences were 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. 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.

Tigecycline-Containing Regimens and Multi Drug-Resistant Acinetobacter baumannii: A Systematic Review and Meta-Analysis.

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.

Evaluation of Tigecycline Utilization and Trends in Antibacterial Resistance from 2018 to 2021 in a Comprehensive Teaching Hospital in China.

Tigecycline, the first glycylcycline antibiotic, which was widely used for off-label indications because of its broad-spectrum antibacterial activity. This study evaluated the indications for clinical use of tigecycline, clinical and microbiological effectiveness, factors associated with in hospital mortality, and bacterial resistance. This retrospective study evaluated all inpatients who received tigecycline treatment for >72 hours between January 2018 and December 2021 in a comprehensive teaching hospital in China. The evaluation included indications, administration regimen, etiology, efficacy and so on. Univariate and multivariate analyses were used to evaluate the risk factors for all-cause mortality. There were 203 patients treated with tigecycline. Tigecycline was commonly prescribed for off-label indications (83.25%, 169/203), and hospital-acquired pneumonia ranked first (79.29%, 134/169). The most common pathogen was Acinetobacter baumannii. Clinical and microbiological success was 57.14% (116/203) and 32.28% (41/127), respectively. Fifty-four patients died and all-cause mortality was 26.60%. Univariate and multivariate analyses showed no significant difference in age, gender, off-label indication, duration of treatment, combination with other drugs, multidrug-resistant or extensively drug-resistant infections and tigecycline application scoring with respect to mortality. Although detection of A. baumannii has decreased in the past 4 years in our hospital, resistance to tigecycline has increased. For clinical application, physicians attach importance to detection of pathogenic microorganisms, but there is still empirical medication without bacterial culture reports. Therefore, an antibiotic stewardship program oriented toward tigecycline should be strengthened to curb bacterial resistance.

P01 A review of tigecycline use in a large teaching hospital trust

Abstract Background Tigecycline is licensed for use in complicated intra-abdominal and complicated skin and soft tissue infections and is listed in seven guidelines at our large teaching hospital trust. Tigecycline is also used when advised by microbiology or infectious diseases. A drug safety update was published by the Medicines and Healthcare products Regulatory Agency (MHRA) in 2011 warning of increased mortality in clinical trials when tigecycline was used compared with other antibiotics. A review was undertaken to identify whether tigecycline was being used appropriately across a year period. Methods Tigecycline is kept as stock on some wards and dispensed individually to patients where stock is not kept. Dispensing data between April 2021 and March 2022 was reviewed. 409 vials were dispensed as stock and 64 patients had tigecycline dispensed directly to them. Results 18 patients (28%) had tigecycline prescribed as per guidelines, 51 (75%) patients had tigecycline prescribed on the advice of microbiology and out of the 25% patients who did not have microbiology involvement, three patients did not have a clear indication for tigecycline use, with no positive microbiology. 9 patients (14%) had tigecycline prescribed as per oesophageal bleed prophylaxis guidelines and one patient for allergy testing purposes. 24 patients (38%) were prescribed tigecycline for licensed indications, with one patient being prescribed it for cellulitis and the rest for complicated intra-abdominal infections. Examples of other indications where tigecycline was used were bacteraemias, pelvic infections, bone and joint infections and line infections. 41 patients (64%) had positive microbiology samples and all of these patients were discussed with microbiology. Most patients had grown vancomycin-resistant enterococci or Enterococcus faecium. See Figure 1 for the range of microbiology sampled. The MHRA update in 2011 advised of an increased mortality rate of 2.3% (52/2216) when using tigecycline for complicated skin and soft tissue and complicated intra-abdominal infections compared with 1.5% (33/2206) in clinical trials, so mortality data was considered as part of this review. 11 patients (17%) of patients died within 28 days of receiving tigecycline. For 5 of these patients, infection was listed on their death certificate, 2 patients did not have infection listed, 1 patient is awaiting an inquest and 3 patients did not have a death certificate listed on their hospital record due to place of death being outside the hospital. Conclusions It is reassuring that most of the tigecycline prescribed is within guidelines or has been discussed with microbiology and use is based on positive samples, with only 3 patients (5%) having no clear reason why tigecycline was prescribed. A limitation of this review was that some patients who received tigecycline across the year period could not be identified using dispensing data only. A future review would be beneficial to examine all the prescribing data from the electronic medicines system and continued monitoring of use and mortality.

The Effect of Widespread Use of Tigecycline and Colistin on Gram-negative Bacteria with Intrinsic Resistance to Tigecycline and Colistin and Investigation of Bacterial Distribution

The Effect of Widespread Use of Tigecycline and Colistin on Gram-negative Bacteria with Intrinsic Resistance to Tigecycline and Colistin and Investigation of Bacterial Distribution

Antibiotic Combination Therapy for Severe Scrub Typhus: Is It Necessary?

Scrub typhus can be adequately treated with doxycycline or azithromycin unless it is treated too late. Such cases present as severe scrub typhus, and their treatment remains a challenging problem. In this article, we briefly review the literature on the treatment of scrub typhus and the limitations of the combination of doxycycline and azithromycin. Several options are suggested for further study in the treatment of severe scrub typhus (such as encephalitis, myocarditis, and pneumonia), including dose escalation of doxycycline, the adjuvant use of steroids, the selective use of beta-lactam antibiotics, and the use of tigecycline.

Voriconazole therapeutic drug monitoring and hepatotoxicity in critically ill patients: A nationwide multi-centre retrospective study

To characterize trough concentrations (Cmin) of voriconazole and associated hepatotoxicity, and to determine predictors of hepatotoxicity and identify high-risk groups in critically ill patients. This was a nationwide, multi-centre, retrospective study. Cmin and hepatotoxicity were studied from 2015 to 2020 in 363 critically ill patients who received voriconazole treatment. Logistic regression and classification and regression tree (CART) models were used to identify high-risk patients. Large interindividual variability was observed in initial voriconazole Cmin and concentrations ranged from 0.1 mg/L to 18.72 mg/L. Voriconazole-related grade ≥2 hepatotoxicity developed in 101 patients, including 48 patients with grade ≥3 hepatotoxicity. The median time to hepatotoxicity was 3 days (range 1-24 days), and 83.2% of cases of hepatotoxicity occurred within 7 days of voriconazole initiation. Voriconazole Cmin was significantly associated with hepatotoxicity. The CART model showed that significant predictors of grade ≥2 hepatotoxicity were Cmin >3.42 mg/L, concomitant use of trimethoprim-sulfamethoxazole or tigecycline, and septic shock. The model predicted that the incidence of grade ≥2 hepatotoxicity among these high-risk patients was 48.3-63.4%. Significant predictors of grade ≥3 hepatotoxicity were Cmin >6.87 mg/L, concomitant use of at least three hepatotoxic drugs, and septic shock; the predictive incidence among these high-risk patients was 22.7-36.8%. Higher voriconazole Cmin, septic shock and concomitant use of hepatotoxic drugs were the strongest predictors of hepatotoxicity. Plasma concentrations of voriconazole should be monitored early (as soon as steady state is achieved) to avoid hepatotoxicity.

Risk factors of tigecycline-associated fibrinogen reduction in patients with renal transplantation: a case-control study.

Hypofibrinogenemia is a serious adverse reaction related to tigecycline administered against multidrug-resistant (MDR) bacteria and can lead to therapy termination. High dose and prolonged tigecycline therapy, renal failure, and base level of fibrinogen (FIB) were reported risk factors of tigecycline-associated FIB reduction. But results are unknown in patients with renal transplantation. A single-center and a case-control study involving renal transplantation patients was conducted. From January, 2017 to January, 2020, patients with a tigecycline course more than 2 days and a baseline FIB level greater than 2 g/L were enrolled. Hypofibrinogenemia was defined as plasma FIB <2.0 g/L. The extent of FIB reduction was calculated based on the baseline of FIB level before tigecycline administration. FIBRO was defined as the extent of FIB reduction over 50%, and FIBRB referred to the extent of FIB reduction below 50%. Univariate and multivariate analyses were performed by logistic regression models to identify independent risk factors of tigecycline-associated FIB reduction. In total, 120 patients were enrolled. A total of 114 patients (95.00%) developed with hypofibrinogenaemia. Hypofibrinogenemia mainly occurred 3 days after tigecycline administration. Of them, 79 (65.83%) developed FIBRO with a median occurrence of 3 [2-4] days after initiation of tigecycline. Multivariable regression analysis demonstrated that the FIB level before tigecycline use [odds ratio (OR): 3.225, 95% confidence interval (CI): 1.801-5.772] and total tigecycline dose (OR: 4.930, 95% CI: 1.433-16.959) were risk factors for FIBRO. The FIB level before tigecycline use and total tigecycline dose were significantly associated with FIBRO, suggesting that FIB level and coagulation-related indicators should be closely monitored during tigecycline treatment to avoid life-threatening bleeding events.