Administration Of Tigecycline Research Articles

Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units

BackgroundWe 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.MethodsThis 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.ResultsFor 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.ConclusionsTigecycline 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.

Clinical Manifestations and Risk Factors of Tigecycline-Associated Thrombocytopenia.

Thrombocytopenia, characterized by a diminished platelet count, emerged as the most frequently reported coagulation dysfunction event according to the FDA Adverse Event Reporting System (FAERS) database. In recent years, numerous clinical studies have investigated the potential link between tigecycline usage and the occurrence of hypofibrinogenemia. However, a research gap remains in comprehensively examining the association between tigecycline and thrombocytopenia in real-world settings. This study was conducted to explore the incidence and clinical manifestations of tigecycline-associated thrombocytopenia. A retrospective case-control study of patients treated with tigecycline was conducted between January 2018 and June 2022. In total, 373 patients were included in this study. Among these patients, 12.3% experienced thrombocytopenia. The onset of thrombocytopenia occurred within a range of 2 to 22 days after the initiation of tigecycline, with a median period (25-75th percentile) of 9 (6-11) days. Among the patients manifesting thrombocytopenia, 60.9% exhibited mild-to-moderate cases (grades 1-2) while 39.1% endured severe cases (grades 3-4). Multivariate analysis delineated several factors as independent risk factors for thrombocytopenia. Notably, advanced age (≥74 years) (p=0.028), risk of malnutrition (p<0.001), tigecycline therapy for ≥7 days (p=0.003), DBIL>8.1μmol/L (p<0.001)), BUN>8.1mmol/L (p=0.002) emerged as independent risk factors associated with thrombocytopenia. When comparing the control group to the thrombocytopenia group, 70.7% of patients in the control group exhibited 0-2 risk factors, while all patients in the thrombocytopenia group demonstrated risk factors. Specifically, 95.7% of patients in the thrombocytopenia group presented with three to five risk factors, with only 4.4% having 0-2 risk factors. Tigecycline administration is associated with thrombocytopenia. Healthcare professionals should exercise vigilance, particularly in cases of severe tigecycline-associated thrombocytopenia, and undertake routine monitoring of patients' platelet counts, especially for those who possess three or more risk factors.

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.

A case report of drug-induced liver injury after tigecycline administration: histopathological evidence and a probable causality grading as assessed by the updated RUCAM diagnostic scale

BackgroundThere have been no reports of tigecycline-associated drug-related liver injury (DILI) identified by histopathological assistance and causal assessment method. We reported the histopathological manifestations for the first time and described tigecycline-associated liver injury’s pattern, severity, duration, and outcome.Case presentationA 68-year-old male with post-liver transplantation was given high-dose tigecycline intravenously (loading dose 200 mg, followed by 100 mg every 12 h) combined with polymyxin B (50,000 units by aerosol inhalation every 12 h) for hospital-acquired pneumonia caused by carbapenem-resistant Klebsiella pneumoniae. At the same time, tacrolimus was discontinued. Liver function was initially normal but started to decline on day 4 of tigecycline. Reducing the dose of tigecycline and resuming tacrolimus could not reverse the deterioration. Therefore, a liver puncture biopsy was performed for further diagnosis, with histopathological findings being cytotoxic injury. The updated RUCAM scale was used to evaluate the causal relationship between tigecycline and liver injury, with the result of 7 points indicating a “probable” causality grading. Methylprednisolone was initiated to treat DILI that was determined to be Grade 1 cholestatic injury. Total bilirubin and transaminase levels returned to normal on day 4 and 11 after tigecycline withdrawal, respectively. Monthly outpatient follow-up showed that the patient’s liver function stayed normal.ConclusionsThis case possessed a significant reference value for differential diagnosis and treatment prognosis of tigecycline-associated DILI. With early diagnosis and timely management, the tigecycline-associated DILI of this patient was successfully reversed.

Coagulation dysfunction events associated with tigecycline: a real-world study from FDA adverse event reporting system (FAERS) database

BackgroundTigecycline has broad-spectrum anti-bacterial activity and often used for critically ill patients with complicated infections. Only a few clinical studies have reported the coagulation disorder induced by tigecycline. The aim of this study was to investigate the association between tigecycline and coagulation dysfunction using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodData from January 2005 to December 2020 in FAERS were retrieved. We investigated the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare tigecycline with the full database and other antibiotics.ResultsThe total number of reports of coagulation dysfunction related to tigecycline as the primary suspect drug was 223. The median time to event of the coagulation dysfunction events was 10 (interquartile range [IQR] 6.75–13) days. 80.72% coagulation-related adverse events appeared within the first 14 days since the initiation of tigecycline administration. The overall ROR (95% CI) for coagulation-related adverse events was 3.55 (3.08, 4.09). The RORs (95% CI) for thrombocytopenia, hypofibrinogenaemia, coagulopathy, activated partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time prolonged were 8.21 (6.34, 10.62), 705.41 (526.81, 944.54), 30.67 (21.92, 42.92), 42.98 (24.85, 74.31), 4.67 (2.51, 8.71), and 27.99 (15.01, 52.19), respectively. In analyses stratified on comparing tigecycline to vancomycin and daptomycin, significant coagulation dysfunction signals were found with the RORs (95% CI) 2.74 (2.34, 3.22) and 3.08 (2.57, 3.70).ConclusionsWe found a strong signal of high frequency of reporting coagulation dysfunction in tigecycline. Health professionals should be aware of the potential coagulation disorders risk and monitor coagulation parameters during anti-bacterial therapy with tigecycline, particularly the need to monitor fibrinogen levels.

Risk Factors for Tigecycline-Associated Hypofibrinogenemia.

BackgroundWith the widespread use of tigecycline, especially in elderly people infected with multidrug-resistant bacteria, the associated coagulation disorders are attracting the attention of clinicians. The risk factors of tigecycline-associated hypofibrinogenemia are still controversial.PurposeThe aims of our study were to explore the related factors of hypofibrinogenemia caused by tigecycline, and to establish the risk assessment criteria for tigecycline-associated hypofibrinogenemia.Patients and MethodsThis was an observational retrospective cohort study of patients treated for at least 3 days with tigecycline. Hypofibrinogenemia was defined as plasma fibrinogen <2.0 g/L. Risk factors were determined using logistic regression analysis, and the risk assessment criteria were identified by using receiver operating characteristic curves.ResultsIn total, 148 patients were included in the analysis, mean age was 77.09±15.11 years old. Ninety patients who developed hypofibrinogenemia during tigecycline treatment with mean plasma fibrinogen of 1.42 g/L were included in the hypofibrinogenemia group, the other 58 patients with mean plasma fibrinogen of 2.68 g/L were included in the normal group. In the multivariate analysis, age (p = 0.035), tigecycline treatment duration (p = 0.044), and baseline fibrinogen level (p = 0.002) were independently associated with hypofibrinogenemia. An age of ≥82 years, ≥9 days of medication, and a baseline fibrinogen level of ≤3.5 g/L were selected for predicting hypofibrinogenemia. Hypofibrinogenemia was independently associated with bleeding (OR 8.96, 95% CI [1.132–70.946], p = 0.038).ConclusionHypofibrinogenemia is a common adverse effect of tigecycline in our study. Elderly patients are more prone to developing hypofibrinogenemia after the administration of tigecycline. It is independently associated with bleeding but not death. The risk assessment criteria can help in the identification of patients with high risk of hypofibrinogenemia.

Risk factors for tigecycline-induced hypofibrinogenaemia.

Hypofibrinogenaemia is major treatment-related adverse event associated with tigecycline therapy, which in some cases can result in treatment termination. We aimed to identify the risk factors for tigecycline-induced hypofibrinogenaemia. We retrospectively retrieved 426 Chinese patients who were undergoing tigecycline therapy≥3days. There were 426 patients treated with tigecycline. The mean age was 60.31±19.23years, and 299 (70.19%) patients were male. Of the patients, 50.5% developed hypofibrinogenaemia and 10.1% of patients developed bleeding. Compared with before treatment, fibrinogen (FIB) significantly decreased after tigecycline was used while prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) significantly increased (all P<.001). There was no statistically significant difference in platelet count, hepatic function, and renal function before and after tigecycline treatment (all P>.05). In analysing relevant risk factors, extension of the tigecycline treatment course was found to be the main risk factor for tigecycline-induced hypofibrinogenaemia. Regardless of whether patients received the standard dose or high dose of tigecycline, the long treatment course group (>14days) had more patients with hypofibrinogenaemia than the routine treatment course group (52.21% vs 40.74%, 48.81% vs 19.44%, all P<.05). Renal failure (whether requiring or not requiring dialysis) is also a risk factor for tigecycline-induced hypofibrinogenaemia (OR [95% CI]: 2.450 [1.335-4.496]). Tigecycline administration has been related to hypofibrinogenaemia, especially patients with renal failure and when long treatment course of tigecycline are used. We recommend that coagulation function be closely monitored in patients with the aforementioned risk factors for tigecycline-induced hypofibrinogenaemia to ensure patient safety.

Tigecycline Therapy for Multi-drug-Resistant Pseudomonas aeruginosa Sepsis Associated with Multi-organ Failure in an Infant with Persistent Arterial Duct. Case Report.

Sepsis is the leading cause of death in infants and children worldwide. The growing drug resistance in nosocomial gram-negative bacteria has resulted in treatment challenges. One of the most common multi-drug-resistant bacteria is Pseudomonas aeruginosa. Resistance to antibiotics used in Pseudomonas aeruginosa infections limits the therapeutic options. We present a tigecycline administration in a 5-month-old infant with patent arterial duct, heart failure, and respiratory failure due to respiratory syncytial virus bronchiolitis with subsequent respiratory distress syndrome and severe sepsis caused by multi-drug-resistant Pseudomonas aeruginosa. Despite combined antibiotic therapy with meropenem, amikacin, and colistin, inflammatory markers increased. Because of life-threatening condition, tigecycline was added to the therapy and was administered intravenously twice daily. Within 48 h, inflammatory markers started to decrease and tigecycline therapy continued for 13 days without adverse effects. Tigecycline used in combination with other antibiotics might be a valuable therapeutic approach in the management of multi-drug-resistant bacteria infections in pediatric patients when conventional antibiotics have failed. Further studies are needed to evaluate the efficacy and safety of tigecycline administration in critically ill pediatric patients.

Tigecycline-associated hypofibrinogenemia in a real-world setting.

Background Tigecycline is a broad-spectrum antibiotic used to treat infections that do not respond to first-line treatments. High-doses and extended treatments are common; therefore, adverse events might be more frequent and severe than those observed in clinical trials. Several case-reports have referred hypofibrinogenemia in patients who received tigecycline. Objective To analyse the impact of tigecycline use on coagulation parameters, and identify which variables could be related with this. Setting The study was performed at Hospital Universitari Vall Hebron, in Barcelona, Spain. Method Observational, retrospective study. All patients older than 18, who received tigecycline for > 72h from January 2016 to March 2018 were included. Clinical and laboratory data from before, during and at the end of tigecycline treatment were retrospectively collected. Differences between means were analyzed using the paired-sample Student's t-test. Binary logistic regression was performed to identify risk factors for hypofibrinogenemia. Main outcome measure Mean difference in fibrinogen plasma concentration and INR, before and at the end of tigecycline treatment. Results 78 patients (mean age 65; SD ± 15.5years) were identified. The most common indications for tigecycline treatment were abdominal (66%), respiratory tract (16%) and skin&soft tissue (10%) infections. High-dose tigecycline was used in 62% of cases and the median duration of treatment was 12days. Hypofibrinogenemia occurred in 12 patients, 5 bleeding events were observed and 4 of them required fibrinogen administration. Tigecycline caused significant alterations in fibrinogen plasma concentration (mean decrease 1.76g/L; IC 95% 1.36 to 2.15) as well as INR (mean increase 0.11; IC 95% 0.05 to 0.17). Both were recovered after treatment cessation. We identified duration of treatment > 4weeks (OR = 6.6), high-dose tigecycline (OR = 4.75) and high protein C levels (OR = 4.2) as independent variables associated with fibrinogen decrease, but not renal impairment. Conclusions Tigecycline administration has been related with hypofibrinogenemia, especially when high-doses of tigecycline are used. Health professionals should be aware of the potentially severe tigecycline-associated hypofibrinogenemia and monitor coagulation during treatment, especially when high-doses of tigecycline are used.

One case of intracranial administration of tigecycline for treatment of extensively drug-resistant Acinetobacter baumannii intracranial infection

One case of intracranial administration of tigecycline for treatment of extensively drug-resistant Acinetobacter baumannii intracranial infection

Observation of tigecycline administration in gram-negative bacteria infected children with ventilator-associated pneumonia

Objective To investigate the efficacy and safety of tigecycline therapy in children with ventilator-associated pneumonia infected by gram-negative bacteria. Methods We conducted a restrospective chart review of children with ventilator-associated pneumonia in a tertiary hospital from May 1, 2012 to April 30, 2017.Inclusion criteria: positive sputum culture result; receiving tigecycline administration of at least 2 days (4 doses). Clinical data and laboratory results were recorded before and after the therapy. Results Twenty-seven children were enrolled, with the in-hospital mortality of 37.0%(10/27). Twenty-seven bacteria strains were recorded, all of which were gram-negative, with Acinetobacter baumanmii took up the most.Most bacteria were susceptible to tigecycline.Median duration of tigecycline was 10 days (3-27 days), 40.7% patients(11/27) got clinically improvement and 44.4%(12/27) got pathogen eradication.Sulperazone was the most concomitantly used antibiotics.Totally 3 dosage models were observed and model 1(loading dose 2 mg/kg, maintain dose 1 mg/kg) and model 2 (loading dose 1.5 mg/kg, maintain dose 1 mg/kg) were the primary.Rate of clinical improvement and microbiology eradication in model 1 group was higher than other groups.No serious adverse effect was detected. Conclusion Tigecycline combined with other agents could be used as salvage therapy in gram-negative bacteria infected ventilator-associated pneumonia children and it is tolerated. Key words: Tigecycline; Ventilator-associated pneumonia; Pediatric intensive care unit; Multidrug resistant; Acinetobacter baumanmii

Preliminary experience with tigecycline treatment for severe infection in children.

Severe infection is a primary cause of mortality in children facing challenges from multidrug-resistant (MDR) pathogens, particularly MDR Acinetobacter baumannii. Tigecycline has an expanded spectrum of antibacterial activity, and some successful instances of its use in children have been reported. We conducted a retrospective chart review of children treated at a tertiary hospital between May 1, 2012 and May 1, 2017 to examine the efficacy and safety of tigecycline in children with severe infection. A total of 110 patients (69 males) were enrolled in this study, including 46 MDR A. baumannii infection patients, encompassing 51 A. baumannii strains. Totally, the median duration of tigecycline therapy was 10days (range, 2-47days), with a clinical improvement rate of 47.27% (52/110). In A. baumannii infection group, the clinical improvement rate was 50% (23/46) and the microbiology eradication rate was 50.98% (26/51). No adverse events were reported during therapy; however, in one case, a 9-year-old boy with hematologic disease developed tooth discoloration.Conclusion: Although some patients benefited from tigecycline, the efficacy and safety of tigecycline should not be overvalued. Additional data from randomized controlled trials are required to assess the administration of tigecycline. What is Known: • Severe infection is a primary cause of mortality in pediatric patients and its treatment is facing challenges from an increasing number of multidrug-resistant (MDR) pathogens. • Tigecycline has an expanded spectrum of antibacterial activity. • Several case reports have indicated that tigecycline could be used as a salvage therapy in children when options are limited or non-existent. What is New: • We found that rate of clinical improvement was different in various groups of different infection. The efficacy of tigecycline should not be overvalued. • Six dosage models and different infection types were observed in our series, with different improvement and eradication rate, indicating that more data are required to identify a proper tigecycline dosage.

Molecular epidemiology and risk factors for colistin- or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients during a 7-year period

A matched 1:2 case–control study was conducted among critically ill patients in order to identify the risk factors of colistin or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae (ColR-Kp, TigR-Kp) bacteraemia. MIC to colistin and tigecycline were determined by Etest. From 224 bacteraemic patients, 46.4% and 29.5% were resistant to colistin and tigecycline, respectively. PCR revealed that 199 isolates carried the blaKPC gene. PCR revealed that no isolate carried the mcr-1 gene. Risk factors for ColR-Kp bacteraemia as compared to patients with bacteraemia by a colistin-susceptible isolate or patients without carbapenemase-producing K. pneumoniae bacteraemia were colistin or tigecycline administration and tracheostomy, while TigR-Kp bacteraemia as compared to either patients with bacteraemia by tigecycline-susceptible isolate or patients without carbapenemase-producing K. pneumoniae bacteraemia were colistin or tigecycline administration, number of comorbidities and prior bacteraemia by a Gram-negative pathogen. Administration of colistin and tigecycline predisposed to development of bacteraemia by either ColR-Kp or TigR-Kp.

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Risk factors and predictors of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii mortality in critically ill bacteraemic patients over a 6-year period (2010-15): antibiotics do matter.

Purpose. Acinetobacter baumannii and Pseudomonas aeruginosa provoke serious infections, especially in intensive care unit (ICU) patients.Methodology. The risk factors and predictors of mortality for P. aeruginosa (n=84; 46 carbapenem-resistant) and A. baumannii (n=129; all carbapenem-resistant) bloodstream infections (BSIs) in an ICU were evaluated. Antibiotic susceptibility testing was performed using the agar disk diffusion method according to EUCAST guidelines. The minimum inhibitory concentration was determined by a gradient method (Etest). Multilocus sequence typing (MLST) was performed for P. aeruginosa during the carbapenem-resistant outbreak in 2014. Epidemiological data were collected from the patients' chart reviews.Results/Key findings. Hospitalization during the summer months, prior KPC-producing Klebsiella pneumoniae (KPC-Kp) BSI, and the administration of tigecycline, aminoglycosides and cortisone were independently associated with P. aeruginosa BSIs. MLST revealed the dissemination of clone ST227, including carbapenem-resistant P. aeruginosa strains. Hospitalization during the summer months, prior KPC-Kp BSI, and the administration of antibiotics, carbapenem and cortisone were independently associated with A. baumannii BSIs. The 30-day mortality rate for P. aeruginosa and A. baumannii BSI was 45.2 and 39.5 %, respectively. Sequential organ failure assessment (SOFA) score at onset, septic shock, age, and prior KPC-Kp BSI were significantly associated with P. aeruginosa BSI mortality. The administration of at least one active antibiotic was identified as a predictor of a good prognosis. Septic shock and simplified acute physiology score (SAPS) II at onset were independently associated with A. baumannii BSI mortality. The administration of at least one active antibiotic and colistin-vancomycin co-administration were identified as predictors of a good prognosis.Conclusion. KPC-Kp infection predisposes ICU patients to BSI by either A. baumannii or P. aeruginosa. The administration of at least one active antibiotic leads to better survival rates.

MMP-9, brain edema, and length of hospital stay of patients with spontaneous supratentorial intracerebral hemorrhage after hematoma evacuation along with the administration of tigecycline

Background: The high plasma level of matrix metalloproteinses–9 (MMP-9) is believed to disrupt the blood-brain barrier (BBB) and cause brain edema, as well as increase patient’s length of hospital stay (LOS). Tigecycline showed ability to reduce the MMP-9 level on study in animals. This study aimed to evaluate whether tigecycline can reduce the plasma levels of MMP-9; brain edema; and LOS of patients with supratentorial spontaneous intracerebral hemorrhage (SSICH).Methods: A randomized clinical trial (RCT) was conducted on 72 SSICH patients who underwent hematoma evacuation in eleven hospitals in Jakarta; 100 mg tigecycline (n=35) or 2 g fosfomycine (n=37) administered intravenously before skin incision as an prophylactic antibiotics to avoid post-operative infections. Plasma levels of MMP-9 were measured in all subjects before and on the first and seventh day after the surgery. Reduction of brain edema was assessed by comparing the extent of brain edema on computed tomography scan (CT scan) before and CT scan after surgery. The length of stay (LOS) was recorded at the time of hospital discharge either survive or death. Data were analyzed using Mann-Whitney and Chi-Square test.Results: There were non-significant statistical differences between two groups in the proportion of subjects with reduced MMP-9 levels on the first day (48% vs 50%; p=0.902; OR=1.1) and seventh day after the surgery (33% vs 48%; p=0.296; OR=1.9); proportion of the subjects with brain edema reduction (86% vs 80%, p=0.58); LOS (median 12 days vs 13 days, p=0.256; LOS ≥15 days 40% vs 27%; p=0.243; OR=1.81; NNT=8).Conclusion: On SSICH patients who underwent hematoma evacuation, tigecycline did not either reduce MMP-9 levels and brain edema or shorthen LOS.

Carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients: risk factors and predictors of mortality.

A significant increase in carbapenemase-producing Klebsiella pneumoniae (CP-Kp) bacteraemias has been observed worldwide. The objective of the present work was to study the risk factors and predictors of mortality of CP-Kp bacteraemias among critically ill patients. During a 4-year period (2012-3015), a matched 1:2 case-control study was conducted. Klebsiella pneumoniae was identified by Vitek 2 technology. Antibiotic susceptibility was performed by the agar disc diffusion method and Etest. The presence of the bla KPC, bla VIM and bla NDM genes was confirmed by polymerase chain reaction (PCR). Epidemiologic data were collected from the intensive care unit (ICU) computerised database. One hundred and thirty-nine patients who developed a CP-Kp bacteraemia were matched with 278 patients. The majority of isolates (128; 92.1%) carried the bla KPC gene, seven carried both bla KPC and bla VIM, three bla VIM and one carried bla NDM. Risk factors for the development of CP-Kp bacteraemia were administration of tigecycline and number of antibiotics administered prior to CP-Kp bacteraemia. Overall, the 30-day mortality was 36.0%. Multivariate analysis revealed septic shock, Simplified Acute Physiology Score II (SAPS II) upon infection onset, adjunctive corticosteroid administration and parenteral nutrition as independent predictors of mortality, while treatment with a combination of appropriate antibiotics was identified as a predictor of good prognosis. Among septic shock patients (n = 74), Sequential Organ Failure Assessment (SOFA) score upon infection onset, adjunctive corticosteroid administration and strain carrying the bla KPC gene were independently associated with mortality, while the administration of combination treatment was identified as a predictor of a good prognosis. The administration of tigecycline predisposes to the induction of bacteraemia. Appropriate antibiotic treatment is associated with better survival, while concomitant corticosteroid treatment is associated with mortality.

Resistance in treating Clostridium difficile infection

Introduction: Clostridium difficile infection is one of the most severe intestinal disturbances that usually occurs to hospitalized patients or patients who have undergone long antibiotic treatment. It commonly manifests as a diarrheal syndrome and has a medical, surgical and epidemiological emergency character. Case presentation: We report the case of a 60-year-old patient known with small bowel resection and secondary chronic diarrhea who was transferred from the Gastroenterology Department with the diagnosis of Clostridium difficile colitis. He received there maximal treatment with vancomycin and metronidazole. In the Infectious Diseases Department, fecal microbiota transplant was performed with the persistence of an accelerated intestinal transit. Subsequently, rescue treatment with tigecycline accompanied by administration of pancreatic enzymes resulted in the resolution of acute diarrhea syndrome. Conclusions: In treatment resistant Clostridium difficile infection, fecal microbiota transplant is a therapeutic solution and could be used from the first episode of colitis. In severe cases, systemic administration of tigecycline is legitimate. Treatment of infection should not be approached isolatedly, but in conjunction with treatment of patient’s comorbidities.

Whole-Genome Analysis of an Extensive Drug-Resistant Acinetobacter Baumannii ST195 Isolate from a Recipient After DCD Renal Transplantation in China

Background/Aims: Infection with Acinetobacter baumannii was emerging as one of the leading causes of mortality after donation after cardiac death transpalantion. Methods: We reported a case of a recipient who underwent DCD renal transplantation and later got infected by A.baumannii. Etests were done to verify the susceptibility test results in clinic. Whole-genome analysis was applied to investigate the resistant mechanism at gene level. Results: The pathogen was isolated from his draining liquid the day after the surgery, and susceptibility test reavealed that it was sensitive to tigecycline. However, the isolate obtained from the draining liquid became tigecycline-resistant after fifteen-day administration of tigecycline. The Susceptibility tests showed that the pathogen recovered from tigecycline resistance and became intermediated to tigecycline. Whole-Genome analysis revealed the genetic level change leading to tigecycline resistance and we identified the location of mutation by comparing the whole genome sequence of the isolates. Three loci were figured out which may contribute to drug resistance, including genes encoding HTH domain protein, MFS transporter and AdeS. Conclusion: Understanding the genetic characteristics associated with drug resistance mechanism and antimicrobial profiles of pathogen is important in controlling infection outbreak and preventing serious complications and gives a new insight into the development of antimicrobial agents.

Porphyromonas pogonae identification from a soft tissue infection: The first human case

We report a first human case of Porphyromonas pogonae causing soft tissue infection in a patient with open fracture. Strong β-hemolytic, aerotolerant, and non-pigmented gram-negative coccobacilli which matched Porphyromonas pogonae by PCR for 16S rRNA genes were identified from the pus specimen. The clinical course of the patient improved with repeated surgical drainage and tigecycline administration.