Tigecycline Monotherapy Research Articles

Comparing the Outcomes of Cefoperazone/Sulbactam-Based and Non-Cefoperazone/Sulbactam-Based Therapeutic Regimens in Patients with Multiresistant Acinetobacter baumannii Infections-A Meta-Analysis.

The addition of sulbactam restores the complete range of cefoperazone activity against bacteria and extends its spectrum of action to include the Acinetobacter species. The effectiveness of cefoperazone/sulbactam against multiresistant Acinetobacter baumannii has not been investigated. The purpose of the current meta-analysis was to compare the efficacy of cefoperazone/sulbactam-based therapeutic regimens and non-cefoperazone/sulbactam-based therapeutic regimens in the treatment of multiresistant Acinetobacter baumannii infections. The current meta-analysis of 10 retrospective studies provides evidence that cefoperazone/sulbactam-based therapeutic regimens are superior to non-cefoperazone/sulbactam-based therapeutic regimens in terms of 30-day mortality and clinical improvement in patients with multiresistant Acinetobacter baumannii infections. The risk of mortality was reduced by 38% among multiresistant Acinetobacter baumannii infections in patients who received cefoperazone/sulbactam-based therapeutic regimens. The cefoperazone/sulbactam-based combination therapy was superior to the cefoperazone/sulbactam monotherapy in terms of 30-day mortality when both therapeutic regimens were compared to the tigecycline monotherapy in patients with multiresistant Acinetobacter baumannii infections.

Colistin monotherapy or combination for the treatment of bloodstream infection caused by Klebsiella pneumoniae: a systematic review and meta-analysis.

Bloodstream infection of Klebsiella pneumoniae (BSI-KP) were associated with increased mortality. Klebsiella pneumoniae was tested to susceptible to colistin by E-test and broth microdilution method in clinical laboratory. This study aimed to assess the efficacy of colistin versus tigecycline, carbapenem monotherapy and combination in the treatment of BSI-KP. Electronic databases such as PubMed, Web of Science and Embase were searched. The last search was in November 24th, 2022, addressing the colistin, carbapenems and tigecycline monotherapy and combination treatments in patients with BSI-KP. The primary outcomes were 30-day or 28-day mortality. OR where available with 95% CI were pooled in random-effects meta-analysis. Following the outlined search strategy, a total of 658 articles were identified from the initial database searching. Six studies, 17 comparisons were included. However, they all were observational design, lacking high-quality randomized controlled trials (RCTs). Moderate or low-quality evidences suggested that colistin monotherapy was associated with an OR = 1.35 (95% CI = 0.62-2.97, P = 0.45, Tau2 = 0.00, I2 = 0%) compared with tigecycline monotherapy, OR = 0.81 (95% CI = 0.27-2.45, P = 0.71, Tau2 = 0.00, I2 = 0%) compared with carbapenem monotherapy. Compared with combination with tigecycline or carbapenem, Colistin monotherapy resulted in OR of 3.07 (95% CI = 1.34-7.04, P = 0.008, Tau2 = 0.00, I2 = 0%) and 0.98 (95%CI = 0.29-3.31, P = 0.98, Tau2 = 0.00, I2 = 0% ), respectively. Colistin, carbapenem and tigecycline monotherapy showed similar treatment effects in patients who suffered from BSI-KP. Compared with colistin monotherapy, colistin combined tigecycline therapy might play the synergism effects. retrospectively registered.

Intra-abdominal infection after tumor surgery: tigecycline combined with β-lactam antibiotics versus tigecycline alone

BackgroundsTigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus β-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery.MethodsThis was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student’s t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication.ResultsIn total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time.ConclusionsTigecycline plus β-lactam wasn’t superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.

Assessment of Effective Antimicrobial Regimens and Mortality-Related Risk Factors for Bloodstream Infections Caused by Carbapenem-Resistant Acinetobacter baumannii.

This study aimed to determine the clinical features, risk factors, and effective antimicrobial therapy for Carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This was a retrospective analysis of data from patients with CRAB bacteremia in a Chinese tertiary hospital between January 2012 and October 2021. Risk factors, predictors of 30-day mortality, and effective antimicrobial therapy for CRAB BSI were identified using logistic and cox regression analyses. Data from 276 patients with Acinetobacter baumannii (AB) BSI were included, of whom 157 (56.9%) had CRAB BSI. The risk factors that were significantly associated with CRAB BSI included previous intensive care unit (ICU) stay (P < 0.001), immunocompromised status (P < 0.001), cephalosporin use (P = 0.014), and fluoroquinolone use (P = 0.007). The 30-day mortality of the CRAB BSI group was 49.7% (78/157). ICU stay after BSI (P = 0.047), sequential organ failure assessment (SOFA) score ≥10 (P < 0.001), and multiple organ failure (MOF) (P = 0.037) were independent predictors of 30-day mortality. Among antibiotic strategies for the treatment of patients with CRAB BSI, we found that definitive regimens containing cefoperazone/sulbactam were superior to those without cefoperazone/sulbactam in reducing the 30-day mortality rate (25.4% vs 53.4%, P = 0.005). After propensity score matching, we observed a significant increase in the 30-day mortality (77.8%vs 33.3%, P = 0.036) in patients receiving tigecycline monotherapy compared to those receiving cefoperazone/sulbactam monotherapy. The mortality rate of patients receiving tigecycline with cefoperazone/sulbactam was also higher than that of patients receiving cefoperazone-sulbactam monotherapy; however, the difference was not significant (28.6%vs 19.0%, P = 0.375). The severity of patient conditions was significantly associated with mortality in patients with CRAB BSI. Those Patients treated with cefoperazone/sulbactam had better clinical prognoses, and tigecycline should be used with caution.

Secondary bacterial infection caused by ST16 NDM-1 and OXA-48-producing colistin and carbapenem-resistant Klebsiella pneumoniae treated with tigecycline in a pregnant woman with COVID-19

During the COVID-19 pandemic, the rapid emergence of carbapenem and colistin-resistant Klebsiella pneumoniae has resulted in an alarming situation worldwide. We aimed to describe secondary infections and antimicrobial use, in a pregnant woman admitted to hospital with COVID-19. A 28-year-old pregnant woman was admitted to the hospital due to COVID-19. According to the clinical conditions, the patient was transferred to the ICU on the second day. She was empirically treated with ampicillin and clindamycin. Mechanical ventilation through an endotracheal tube was started on the 10th day. During her hospitalization in the ICU, she was infected with ESBL-producing K. pneumonia, Enterobacter spp and carbapenemase-producing colistin-resistant Klebsiella pneumoniae isolates. Finally, the patient was treated with tigecycline monotherapy that was associated with ventilator-associated pneumonia clearance. Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. Treatment of infections caused by carbapenemase-producing colistin-resistant K. pneumoniae isolates is challenging, with limited antimicrobials available in Iran. In order to prevent the spread of extensively drug-resistant bacteria, infection control programs must be implemented more seriously.

Efficacy and Safety of Colistin versus Tigecycline for Multi-Drug-Resistant and Extensively Drug-Resistant Gram-Negative Pathogens-A Meta-Analysis.

Background: We intended to compare the efficacy and safety outcomes of colistin versus tigecycline as monotherapy or combination therapy against multi-drug resistant (MDR) and extensively drug-resistant (XDR) pathogens. Methods: A search was conducted in PubMed, Cochrane CENTRAL, EMBASE, and in the grey literature (i.e., ClinicalTrials.gov and Google Scholar) up to May 2021. Outcomes were clinical response, mortality, infection recurrence, and renal and hepatic toxicity. We pooled odd ratios (OR) using heterogeneity-guided random or fixed models at a statistical significance of p < 0.05. Results: Fourteen observational studies involving 1163 MDR/XDR pathogens, receiving tigecycline versus colistin monotherapy or combination, were included. Base-case analyses revealed insignificant differences in the clinical response, reinfection, and hepatic impairment. The 30-day mortality was significantly relatively reduced with tigecycline monotherapy (OR = 0.35, 95% CI 0.16−0.75, p = 0.007). The colistin monotherapy significantly relatively reduced in-hospital mortality (OR = 2.27, 95%CI 1.24−4.16, p = 0.008). Renal impairment rates were lower with tigecycline monotherapy or in combination, and were lower with monotherapy versus colistin-tigecycline combination. Low-risk of bias and moderate/high evidence quality were associated with all studies. Conclusions: Within the limitations of this study, it can be concluded that there were no statistically significant differences in main efficacy outcomes between colistin and tigecycline monotherapies or combinations against MDR/XDR infections, except for lower rates of 30-day mortality with tigecycline and in-hospital mortality with colistin. Tigecycline was associated with favourable renal toxicity outcomes.

Ceftazidime-Avibactam-Based Versus Tigecycline-Based Regimen for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae-Induced Pneumonia in Critically Ill Patients.

IntroductionThe aim of the present study was to assess the safety profile and outcomes of a ceftazidime–avibactam (CAZ-AVI)-based regimen and compare them with those of a tigecycline (TGC)-based regimen in intensive care unit (ICU) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP), which is classified into hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).MethodsClinical and microbiological cure rates, 28-day survival rates, and safety evaluation findings were compared between patients treated with CAZ-AVI-based regimen and those treated with TGC-based regimen in this retrospective study. Conventional multivariate logistic regression analysis and regression adjustment analysis with propensity score (PS) were performed to control for confounding variables.ResultsA total of 105 cases of critically ill ICU patients with CRKP-induced HAP or VAP were included in the present study from July 2019 to September 2020; 62 patients (59%) received TGC-based regimen and 43 patients (41%) received CAZ-AVI-based regimen. The most common concomitant agent in the CAZ-AVI group and TGC group was carbapenem (44.2% versus 62.9%, P = 0.058), while only a small proportion of the study population received CAZ-AVI and TGC monotherapy (20.9% versus 6.5%, P = 0.027). The clinical and microbiological cure rates of the CAZ-AVI group were superior to those of the TGC group [51.2% versus 29.0% (P = 0.022) and 74.4% versus 33.9% (P < 0.001), respectively]. No significant differences in the 28-day survival rates were identified between the two groups (69.8% versus 66.1%, P = 0.695). Conventional multivariate logistic regression and PS analyses showed that patients who had used CAZ-AVI were more likely to have achieved a clinical cure [4.767 (95%CI 1.694-13.414), P=0.003;3.405 (95%CI 1.304-8.889), P=0.012] and microbiological success [6.664 (95%CI 2.626-16.915), P<0.001;7.778 (95%CI 2.717-22.265), P<0.001] than patients who used TGC. However, the difference in the 28-day survival rates between the two groups was not significant. According to the safety evaluation findings, the CAZ-AVI group exhibited a generally lower incidence of adverse reactions compared with that in the TGC group.ConclusionsCAZ-AVI may be a suitable alternative for TGC in the treatment of critically ill patients with CRKP-induced HAP or VAP. These observations require further confirmation in larger randomized prospective clinical trials.

Anti-tumor activity of tigecycline: a review

Tigecycline is a novel glycylcycline antibacterial drug, which shows both antibiotic function and anti-tumor activity. This review summarizes the single and combined use of tigecycline for tumor treatment and the underpinning mechanisms. As an inhibitor for mitochondrial DNA translation, tigecycline affects the proliferation, migration, and invasion of tumor cells mainly through inhibiting mitochondrial protein synthesis and inducing mitochondrial dysfunction. Although the effect of tigecycline monotherapy is controversial, the efficacy of combined use of tigecycline is satisfactory. Therefore, it is important to explore the molecular mechanisms underpinning the anti-tumor activity of tigecycline, with the aim to use it as a cheap and effective new anti-tumor drug.

Benzydamine Reverses TMexCD-TOprJ-Mediated High-Level Tigecycline Resistance in Gram-Negative Bacteria.

Recently, a novel efflux pump gene cluster called tmexCD1-toprJ1 and its variants have been identified, which undermine the antibacterial activity of tigecycline, one of the last remaining options effective against multidrug-resistant (MDR) Gram-negative bacteria. Herein, we report the potent synergistic effect of the non-steroidal anti-inflammatory drug benzydamine in combination with tigecycline at sub-inhibitory concentrations against various temxCD-toprJ-positive Gram-negative pathogens. The combination of benzydamine and tigecycline killed all drug-resistant pathogens during 24 h of incubation. In addition, the evolution of tigecycline resistance was significantly suppressed in the presence of benzydamine. Studies on the mechanisms of synergism showed that benzydamine disrupted the bacterial proton motive force and the functionality of this kind of novel plasmid-encoded resistance-nodulation-division efflux pump, thereby promoting the intracellular accumulation of tigecycline. Most importantly, the combination therapy of benzydamine and tigecycline effectively improved the survival of Galleria mellonella larvae compared to tigecycline monotherapy. Our findings provide a promising drug combination therapeutic strategy for combating superbugs carrying the tmexCD-toprJ gene.

Efficacy and safety of tigecycline for complicated urinary tract infection: a systematic review.

BackgroundFacing the global threat of emerging resistance to antibiotics, tigecycline, a novel glycylcycline antibiotic, is developed to against multidrug-resistant pathogens, but not recommended for the treatment of complicated urinary tract infection (cUTI). We performed a summary of the literatures to characterize and evaluate the efficacy and safety of tigecycline in patients with cUTI.MethodsWe searched PubMed, EMBASE, Cochrane and Clinical Trials using appropriate syntax to retrieve potential articles up to Jan 2020. General information, pathogen, medication regimen, comorbidities of patients from eligible literatures were recorded. Univariate logistic regression analysis was used to detect the potential factors associated with clinical cure.ResultsNineteen articles comprising 31 cases were included. The subpopulation with transplantation (25.8% of the patients) was the most common comorbidity, and cUTIs were mainly caused by Klebsiella pneumoniae (K. pneumoniae) (48.28%) in our research. Tigecycline 100 mg per day as monotherapy was most common. Clinical cure was reported as majority (77.4%), and microbiological eradication cases accounted for the most (65.2%) among the clinical cure cases. Univariate analysis showed that K. pneumoniae caused cUTI and tigecycline as a single treatment have significant meaning to clinical outcomes (P=0.044 and P=0.034, respectively).ConclusionsClinical and microbiological outcomes of tigecycline treatment revealed high rate of successful response. Tigecycline monotherapy may have a role in the treatment of cUTI except that caused by the pathogen K. pneumoniae. Further randomized controlled trials was still needed to evaluate tigecycline monotherapy for cUTI.

Impact of Tigecycline's MIC in the Outcome of Critically Ill Patients with Carbapenemase-Producing Klebsiella pneumoniae Bacteraemia Treated with Tigecycline Monotherapy-Validation of 2019's EUCAST Proposed Breakpoint Changes.

Background: Tigecycline is a therapeutic option for carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Our aim was to evaluate the impact of the tigecycline’s minimum inhibitory concentration (MIC) in the outcome of patients with CP-Kp bacteraemia treated with tigecycline monotherapy. Methods: Patients with monomicrobial bacteraemia due to CP-Kp that received appropriate targeted monotherapy or no appropriate treatment were included. Primary outcome was 30-day mortality. MICs of meropenem, tigecycline, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. PCR for blaKPC, blaVIM, blaNDM, and blaOXA genes was applied. Results: Among 302 CP-Kp bacteraemias, 32 isolates (10.6%) showed MICs of tigecycline ≤ 0.5 mg/L, whereas 177 (58.6%) showed MICs that were 0.75–2 mg/L. Colistin and aminoglycoside susceptibility was observed in 43.0% and 23.8% of isolates, respectively. The majority of isolates carried blaKPC (249; 82.5%), followed by blaVIM (26; 8.6%), both blaKPC and blaVIM (16; 5.3%), and blaNDM (11; 3.6%). Fifteen patients with tigecycline MIC ≤ 0.5 mg/L and 55 with MIC 0.75–2 mg/L were treated with tigecycline monotherapy; 30-day mortality was 20.0% and 50.9%, respectively (p = 0.042). Mortality of 150 patients that received other antimicrobials was 24.7%; among 82 patients that received no appropriate treatment, mortality was 39.0%. No difference in 30-day mortality was observed between patients that received tigecycline (MIC ≤ 0.5 mg/L) or other antimicrobials. Conclusion: Tigecycline monotherapy was as efficacious as other antimicrobials in the treatment of bloodstream infections due to CP-Kp isolates with a tigecycline’s MIC ≤ 0.5 mg/L.

Characteristics and predictors of treatment failure with intravenous tigecycline monotherapy among adult patients with severe Clostridioides (Clostridium) difficile infection: a single-centre observational cohort study

Our aim was to analyze characteristics of treatment failure with intravenous tigecycline monotherapy among adults with severe Clostridioides (Clostridium) difficile infection (CDI). A single-centre observational cohort study was performed between 2014 and 2018. Data were collected by charts review, diagnosis and severity were determined by ESCMID guidelines. Primary outcome was treatment failure, secondary outcomes were in-hospital mortality, relapse, colectomy, and complication rates. Independent predictors of failure were identified using logistic regression. Altogether 110 patients were included, failure occurred in 37.3%. Patients with failure frequently had chronic heart and pulmonary co-morbidities, peritonitis, higher CRP levels, ICU admittance rates and need for total parenteral nutrition and vasopressors. Mostly, CDI-specific mortality and complications contributed to failure. Relapse rates were similar. Chronic pulmonary disease, ileus, total parenteral nutrition, and duration of tigecycline therapy were predictors of failure. We conclude that severe CDI cases with higher risk for tigecycline monotherapy failure might be identified by contributing factors.

Successful High-Dosage Monotherapy of Tigecycline in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats.

Background: Recent scientific reports on the use of high dose tigecycline monotherapy as a “drug of last resort” warrant further research into the use of this regimen for the treatment of severe multidrug-resistant, Gram-negative bacterial infections. In the current study, the therapeutic efficacy of tigecycline monotherapy was investigated and compared to meropenem monotherapy in a newly developed rat model of fatal lobar pneumonia–septicemia. Methods: A Klebsiella pneumoniae producing extended-spectrum β-lactamase (ESBL) and an isogenic variant producing K. pneumoniae carbapenemase (KPC) were used in the study. Both strains were tested for their in vitro antibiotic susceptibility and used to induce pneumonia–septicemia in rats, which was characterized using disease progression parameters. Therapy with tigecycline or meropenem was initiated at the moment that rats suffered from progressive infection and was administered 12-hourly over 10 days. The pharmacokinetics of meropenem were determined in infected rats. Results: In rats with ESBL pneumonia–septicemia, the minimum dosage of meropenem achieving survival of all rats was 25 mg/kg/day. However, in rats with KPC pneumonia–septicemia, this meropenem dosage was unsuccessful. In contrast, all rats with KPC pneumonia–septicemia were successfully cured by administration of high-dose tigecycline monotherapy of 25 mg/kg/day (i.e., the minimum tigecycline dosage achieving 100% survival of rats with ESBL pneumonia–septicemia in a previous study). Conclusions: The current study supports recent literature recommending high-dose tigecycline as a last resort regimen for the treatment of severe multidrug-resistant bacterial infections. The use of ESBL- and KPC-producing K. pneumoniae strains in the current rat model of pneumonia–septicemia enables further investigation, helping provide supporting data for follow-up clinical trials in patients suffering from severe multidrug-resistant bacterial respiratory infections.

Tigecycline versus INR increase; more than expected?

ABSTRACT Objectives: The aim of the study was to investigate the frequency of tigecycline-associated INR abnormality. Methods: Patients who were hospitalized between June and September 2016 and treated with tigecycline including therapy were extracted from hospital database and retrospectively reviewed. INR values at the beginning and end of treatment were compared. Results: A total of 79 patients who received tigecycline were identified by analyzing the hospital database. Nineteen patients were excluded from the study since INR was not measured at the beginning and/or end of treatment. In 55 of the 60 patients, INR levels were within normal limits (0.9–1.2) at the beginning of treatment while 19 of these 55 (34,5%) had prolonged INR after treatment. Prolongation was found to be mild (1.01–1.25 x ULN-upper limit of normal) in 12 of 19 patients, moderate (1.26–1.5 x ULN) in six and severe (1.51−3.0 x ULN) in one. In 10 of 19 patients, tigecycline was stopped, and the INR values normalized. There was no difference in INR abnormality rate between tigecycline monotherapy versus combination therapy receiving cases (19/27–33% vs. 10/33–30% p:1). Conclusion: These data show that INR prolongation may develop as common as 34.6% during tigecycline therapy. Regular INR follow-up may be beneficial in cases receiving tigecycline.

Efficacy of tigecycline monotherapy versus combination therapy with other antimicrobials against carbapenem-resistant Acinetobacter baumannii sequence type 2 in Heilongjiang Province.

Selecting alternative antibiotic combinations as treatment options may help successfully manage carbapenem-resistant Acinetobacter baumannii (CRAB). This study aimed to determine the synergistic effects of tigecycline (TIG) monotherapy versus combination therapy with other antimicrobials against CRAB. After performing biochemical identification assays, we detected oxacillin-hydrolyzing (OXA)-type carbapenemase genes in 35 CRAB isolates. The minimum inhibitory concentrations (MICs) and interactions of the test drugs were determined using the checkerboard assay with TIG, colistin (CST) and meropenem (MEM). Static time-kill assays were conducted to validate the synergistic effects of the most efficacious combination. The chromosomal gene, blaOXA-51-like, was tested among all isolates, blaOXA-23-like and blaOXA-24-like were present in 91.4% and 25.7%, respectively. In the checkerboard assay, the combination of TIG and MEM displayed the highest rate of synergy (30.5%) against the 35 isolates. In contrast, the TIG-CST combination showed a higher indifference interaction rate (36.1%) than that of the TIG-MEM (16.7%) combination. Antagonism appeared in one isolate for the TIG-CST combinations. The static time-kill assays confirmed the superior synergistic effect of CST against the CRAB isolates. TIG combined with CST exhibited early synergistic activity that was not sustained beyond 12 h. TIG combination therapy can only be recommended when other optimized therapeutics are unavailable.

Once-a-week tigecycline for the treatment of drug-resistant TB.

MDR-TB and XDR-TB have poor outcomes. To examine the efficacy of tigecycline monotherapy in the hollow fibre system model of TB. We performed pharmacokinetic/pharmacodynamic studies using tigecycline human-like concentration-time profiles in the hollow fibre system model of TB in five separate experiments using Mycobacterium tuberculosis in log-phase growth or as semi-dormant or intracellular bacilli, as monotherapy. We also compared efficacy with the isoniazid/rifampicin/pyrazinamide combination (standard therapy). We then applied extinction mathematics, morphisms and Latin hypercube sampling to identify duration of therapy with tigecycline monotherapy. The median tigecycline MIC for 30 M. tuberculosis clinical and laboratory isolates (67% MDR/XDR) was 2 mg/L. Tigecycline monotherapy was highly effective in killing M. tuberculosis in log-phase-growth and semi-dormant and intracellular M. tuberculosis. Once-a-week dosing had the same efficacy as daily therapy for the same cumulative dose; thus, tigecycline efficacy was linked to the AUC0-24/MIC ratio. Tigecycline replacement by daily minocycline after 4 weeks of therapy was effective in sterilizing bacilli. The AUC0-24/MIC ratio associated with optimal kill was 42.3. Tigecycline monotherapy had a maximum sterilizing effect (day 0 minus day 28) of 3.06 ± 0.20 log10 cfu/mL (r2 = 0.92) compared with 3.92 ± 0.45 log10 cfu/mL (r2 = 0.80) with optimized standard therapy. In our modelling, at a tigecycline monotherapy duration of 12 months, the proportion of patients with XDR-TB who reached bacterial population extinction was 64.51%. Tigecycline could cure patients with XDR-TB or MDR-TB who have failed recommended therapy. Once-a-week tigecycline could also replace second-line injectables in MDR-TB regimens.

Tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii meningitis: Results of the Ege study

ObjectivesIn this study we retrospectively reviewed A. baumannii meningitis cases treated with tigecycline including regimens and evaluated the efficacy of tigecycline in the therapy.Patients and Methods: Study was performed in seven tertiary-care educational hospitals from five cities of Turkey and one center from France. We extracted data and outcomes of all adult (aged >18) patients with culture proven A. baumannii meningitis treated with tigecycline including antibiotic therapy until April 2016. ResultsA total of 23 patients (15 male and eight female) fulfilled our inclusion criteria. All Acinetobacter strains were carbapenem-resistant and susceptible to tigecycline. Six cases received tigecycline monotherapy while 17 received tigecycline including combination therapy (10 with colistin, 4 with netilmicin, 3 with amikacin, 4 with meropenem). Seven of 23 cases (30%) died during the tigecycline including therapy (1 in monotherapy, 4 in colistin, 2 in netilmicin, 1 amikacin, one case received tigecycline + netilmicin followed by tigecycline + colistin). Hence, overall end of treatment (EOT) success was 70%. However, since further 27% died due to additional nosocomial infections, overall clinical success (relieved symptoms at the EOT and one-month post-therapy survival without any relapse or reinfection) decreased to 43%. ConclusionWe conclude that tigecycline may be an alternative in the salvage treatment of nosocomial multidrug-resistant Acinetobacter spp. meningitis. Acinetobacter spp. Meningitis.

Efficacy and safety of tigecycline monotherapy versus combination therapy for the treatment of hospital-acquired pneumonia (HAP): a meta-analysis of cohort studies

The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.

Antibiotic strategies and clinical outcomes in critically ill patients with pneumonia caused by carbapenem-resistant Acinetobacter baumannii

ObjectivesThis study aimed to investigate antibiotic prescribing patterns and effectiveness of different anti-carbapenem-resistant Acinetobacter baumannii (CRAB) strategies for CRAB pneumonia. MethodsWe conducted a multicentre, retrospective study in three hospitals. During 2010–2015, adult ICU patients with CRAB pneumonia treated with at least one antimicrobial agent covering the CRAB isolate in vitro for more than 2 days were included. We used multivariate logistic regression to analyse the associations of anti-CRAB strategies with ICU mortality and other clinical outcomes. ResultsAmong 238 patients with CRAB pneumonia, tigecycline monotherapy (84, 35.3%) was the most common antibiotic strategy, followed by tigecycline with colistin (43, 18.1%), colistin monotherapy (34, 14.3%), colistin combination without tigecycline (33, 13.9%), tigecycline combination without colistin (32, 13.4%), and sulbactam-based therapy without tigecycline and colistin (12, 5.0%). In multivariate analysis, tigecycline-based therapy was associated with higher ICU mortality than non-tigecycline therapy (adjusted OR 2.30, 95% CI 1.19–4.46). There was no difference between colistin-based therapy and non-colistin therapy. Compared with tigecycline monotherapy, colistin monotherapy was associated with lower ICU mortality (aOR 0.30, 95% CI 0.10–0.88). Treatment failure analyses showed similar trends. Tigecycline-based therapy was associated with higher treatment failure rate than non-tigecycline therapy (aOR 2.51, 95% CI 1.39–4.54), whereas colistin-based therapy was associated with lower treatment failure rate than non-colistin-based therapy (aOR 0.48, 95% CI 0.27–0.86). ConclusionsTigecycline was commonly prescribed for CRAB pneumonia. However, tigecycline-based therapy was associated with higher ICU mortality and treatment failure. Our study suggests that colistin monotherapy may be a better antibiotic strategy for CRAB pneumonia.

Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.