In 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were first published in the Journal of Hepato-Biliary-Pancreatic Surgery. The fundamental policy of TG07 was to achieve the objectives of TG07 through the development of consensus among specialists in this field throughout the world. Considering such a situation, validation and feedback from the clinicians’ viewpoints were indispensable. What had been pointed out from clinical practice was the low diagnostic sensitivity of TG07 for acute cholangitis and the presence of divergence between severity assessment and clinical judgment for acute cholangitis. In June 2010, we set up the Tokyo Guidelines Revision Committee for the revision of TG07 (TGRC) and started the validation of TG07. We also set up new diagnostic criteria and severity assessment criteria by retrospectively analyzing cases of acute cholangitis and cholecystitis, including cases of non-inflammatory biliary disease, collected from multiple institutions. TGRC held meetings a total of 35 times as well as international email exchanges with co-authors abroad. On June 9 and September 6, 2011, and on April 11, 2012, we held three International Meetings for the Clinical Assessment and Revision of Tokyo Guidelines. Through these meetings, the final draft of the updated Tokyo Guidelines (TG13) was prepared on the basis of the evidence from retrospective multi-center analyses. To be specific, discussion took place involving the revised new diagnostic criteria, and the new severity assessment criteria, new flowcharts of the management of acute cholangitis and cholecystitis, recommended medical care for which new evidence had been added, new recommendations for gallbladder drainage and antimicrobial therapy, and the role of surgical intervention. Management bundles for acute cholangitis and cholecystitis were introduced for effective dissemination with the level of evidence and the grade of recommendations. GRADE systems were utilized to provide the level of evidence and the grade of recommendations. TG13 improved the diagnostic sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates adapted for clinical practice. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many new diagnostic and therapeutic modalities were presented. The bundles for the management of acute cholangitis and cholecystitis are presented in a separate section in TG13.

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TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis

Summary Background Multidrug resistance among bacteria increases the need for new antimicrobial drugs with high potency and stability. Tigecycline is one candidate drug, and a previous meta-analysis of only published randomised controlled trials suggested that it might as effective as comparator treatments; we did a meta-analysis to include new and unpublished trials to assess its efficacy for the treatment of adult patients with serious bacterial infection. Methods We searched PubMed, Cochrane Central Register, and Embase up to March 30, 2011, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. Eligible studies were randomised trials assessing the clinical efficacy, safety, and eradication efficiency of tigecycline versus other antimicrobial agents for any bacterial infection. The primary outcome was treatment success in patients who received at least one dose of the study drug, had clinical evidence of disease, and had complete follow-up (the clinically assessable population). Meta-analysis was done with random-effects models because of heterogeneity across the trials. Findings 14 randomised trials, comprising about 7400 patients, were included. Treatment success was lower with tigecycline than with control antibiotic agents, but the difference was not significant (odds ratio 0·87, 95% CI 0·74–1·02). Adverse events were more frequent in the tigecycline group than in the control groups (1·45, 1·11–1·88), with significantly more vomiting and nausea. All-cause mortality was higher in the tigecycline group than in the comparator groups, but the difference was not significant (1·28, 0·97–1·69). Eradication efficiency did not differ between tigecycline and control regimens, but the sample size for these comparisons was small. Interpretation Tigecycline is not better than standard antimicrobial agents for the treatment of serious infections. Our findings show that assessment with unpublished studies is needed to make appropriate decisions about new agents. Funding None.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(11)70177-3.pdf

Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis

OBJECTIVES To describe antimicrobial susceptibility among bacterial isolates associated with hospital infections collected from 266 centres in Asia/Pacific Rim (n = 1,947), North America (n = 24,283), Latin America (n = 1,957) and Europe (n = 8,796) METHODS Isolates were collected from blood, respiratory tract, urine, skin, wound, body fluids and other defined sources between January 2004 and August 2006 Only one isolate per patient was accepted In vitro MICs for the isolates were determined according to the CLSI (formerly NCCLS) guidelines RESULTS Key organisms collected were Acinetobacter baumannii (n = 2,902), Enterobacter spp (n = 5,731), Escherichia coli (n = 6,504), Klebsiella pneumoniae (n = 4,916), Pseudomonas aeruginosa (n = 5,128), Serratia marcescens (n = 2,313), Enterococcus faecalis (n = 2,701), Enterococcus faecium (n = 1,035) and Staphylococcus aureus (n = 5,753) Rates of methicillin resistance among S aureus and of vancomycin resistance among enterococci were highest in North America (2,016/3,809, 529% and 571/2,544, 224%, respectively) and lowest in Europe (337/1,340, 251% and 36/916, 39%, respectively) Tigecycline was the only antimicrobial to maintain activity against all Gram-positive isolates (MIC(90) values of 93% susceptibility in all regions) antimicrobials against the Gram-negative species, except for A baumannii and P aeruginosa Piperacillin/tazobactam and amikacin were the most active against P aeruginosa Extended-spectrum beta-lactamase producers among K pneumoniae occurred most frequently in Latin America (124/282, 440%) CONCLUSIONS Tigecycline is a novel broad-spectrum antimicrobial that is active against the common organisms associated with infections

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Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline

The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). A meta-analysis of randomized controlled trials (RCTs) identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs involving 4,651 patients were included in the meta-analysis. Compared with therapy with empirical antibiotic regimens, tigecycline monotherapy was associated with similar clinical treatment success rates (for the clinically evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.76 to 1.12, P = 0.42; for the clinical modified intent-to-treat [c-mITT] population, OR = 0.86, 95% CI = 0.74 to 1.01, P = 0.06) and similar microbiological treatment success rates (for the microbiologically evaluable [ME] population, OR = 0.86, 95% CI = 0.69 to 1.07, P = 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR = 1.33, 95% CI = 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.

Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease

Clostridium difficile infection (CDI) has become more refractory to standard therapy. We describe 4 patients with severe refractory CDI who were successfully treated with tigecycline. Symptoms improved within 1 week. No relapses were observed. This favorable outcome suggests that tigecycline might be a useful alternative for treating severe refractory CDI.

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Intravenous Tigecycline as Adjunctive or Alternative Therapy for Severe Refractory Clostridium difficile Infection

Tigecycline: A glycylcycline antimicrobial agent

Background:Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics.Study Design:Systematic literature review of prevalence, mechanisms, and clinical implications in S

Thien Ly Doan

Papers

Tigecycline: A glycylcycline antimicrobial agent

Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications