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• The prevalence of carbapenem-resistant Acinetobacter baumannii (CR-AB) varied among countries. • Of 232 CR-AB isolates, 224 (96.6%) harbored at least one carbapenemase gene. • Of the 226 carbapenemase genes detected, bla OXA-23 was the most dominant (94.7%). • CR-AB showed varied resistance rates for minocycline, colistin, and tigecycline. This study aimed to investigate the geographic distribution of carbapenem-resistant Acinetobacter baumannii (CR-AB) isolates in the Asia-Pacific region. We collected A. baumannii isolates using the Antimicrobial Testing Leadership and Surveillance program from 2012 to 2019. The minimum inhibitory concentrations (MICs) of the isolates were determined using the broth microdilution method. The major carbapenemase genes were identified using multiplex polymerase chain reaction assays for the isolates collected between 2012 and 2014. CR-AB was defined as isolates with meropenem MICs ≥8 mg/l. In total, 2674 A. baumannii isolates were collected from 13 countries, of which 1918 (71.7%) were CR-AB. The carbapenem resistance rates among A. baumannii isolates were as low as 2.8% and 6.5% in Japan and Australia, respectively, but as high as 88% and 87.2% in South Korea and India, respectively. Of the 232 CR-AB isolates that underwent carbapenemase gene screening, 224 (96.6%) harbored at least one carbapenemase gene. A total of 226 carbapenemase genes were detected, with bla OXA-23 (94.7%, 214/226) being the most dominant, followed by bla OXA-72 (2.7%, 6/226), bla OXA-58 (2.2%, 5/226), and bla NDM-1 (0.4%, 1/226). CR-AB isolates had >80% resistance to amikacin, ampicillin/sulbactam, cefepime, ceftazidime, ciprofloxacin, levofloxacin, and piperacillin/tazobactam. The rates of CR-AB resistance to minocycline and colistin were 7.2% (31/429) and 1.7% (23/1368). For cefoperazone/sulbactam and tigecycline, 50.2% (527/1049) and 93.3% (1789/1918) of CR-AB isolates had an MIC ≤16 mg/l and ≤2 mg/l, respectively. The prevalence of carbapenem resistance in A. baumannii showed significant differences among countries in the Asia-Pacific region, and the treatment options were limited. [ABSTRACT FROM AUTHOR]

• Tigecycline treatment causes a significant decrease in fibrinogen levels. • Tigecycline exposure is highly predictive of hypofibrinogenemia. • Serum concentration at the 6 hours after the dosing (C 1/2) ≥ 0.645 mg/l with best predictive performance may be the optimal toxicity threshold. This study aimed to determine the thresholds of serum concentration as a predictor of tigecycline (TGC)-induced hypofibrinogenemia (HF) in critically ill patients. A retrospective cohort study was conducted in intensive care unit patients treated with TGC. The clinical data and serum concentration were extracted from the patients' electronic medical records. Patients were divided into an HF group and a normal group according to fibrinogen value. The receiver operating characteristic curves and logistic regression were used to derive serum concentration thresholds and quantify the association between exposure thresholds and HF while adjusting for confounders. In total, 100 patients were included. The receiver operating characteristic curves analysis showed that TGC concentration parameters were strongly predictive of HF. Adjusting for duration of TGC, serum concentration at the 6 hours after the dosing (C 1/2) ≥ 0.645 mg/l, area under the concentration-time curve over a 24-hour period (AUC 0-24) ≥ 20.76 mg·h/l, and serum concentration of 30 minutes before next dose (C min) ≥ 0.455 mg/l were associated with a three- to five-fold increased risk of TGC-induced HF in logistic regression. The findings from this study provide evidence that TGC exposure is highly predictive of HF, with an approximately three- to five-fold increased risk. Serum concentration at the 6 hours after the dosing (C 1/2) ≥ 0.645 mg/l with best area under the receiver operating characteristic curve and negative predictive value appears to be the most appropriate toxicity threshold. [Display omitted] [ABSTRACT FROM AUTHOR]

• This is the first multicenter retrospective study about tigecycline drug-induced liver injury (DILI). • The prevalence of tigecycline DILI in the study population was 10.3%. • Abnormal baseline alanine aminotransferase, intensive care unit admission, and treatment length were risk factors. We conducted this multicenter retrospective study to evaluate the prevalence, clinical patterns, and risk factors for tigecycline-induced liver injury, which is a type of drug-induced liver injury (DILI). Inpatients receiving intravenous tigecycline for ≥7 days were included. Patient information was collected to assess possible DILIs. The pattern and severity of tigecycline DILI were evaluated. A multivariable logistic regression model was used to identify the independent risk factors associated with tigecycline DILI. A total of 986 patients were identified and 397 patients were included in this study. The prevalence of tigecycline DILI was 10.3% (95% confidence interval [CI] = 7.51–13.7%). The most common type of tigecycline DILI was cholestatic, with mild severity observed in most cases. Abnormal baseline alanine aminotransferase levels (odds ratio [OR] = 3.11, 95% CI = 1.55–6.24, P = 0.001), intensive care unit admission (OR = 2.63, 95% CI = 1.32–5.36, P = 0.006), and treatment length (in weeks) (OR = 1.25, 95% CI = 1.05–1.49, P = 0.011) were independent risk factors for tigecycline DILI. Our results indicate that the prevalence of tigecycline DILI is high, and that the patients at risk should receive special attention. [Display omitted] [ABSTRACT FROM AUTHOR]

• The patients in the HD group had a higher clinical cure rate than those in the SD group. • The Cmax, C1/2, Cmin, AUC and AUIC in the cured group were higher than those in the failure group. • The MICs were dramatically higher in the failure group than those in the cure group. • AUIC and MIC are independent risk factors for prognosis. Based on pharmacokinetics/pharmacodynamics (PK/PD) and the minimum inhibitory concentration (MIC) of tigecycline (TGC), dose increases have been advocated to maximize the efficacy against pneumonia that is suspected to be due to multidrug-resistant (MDR) bacteria in an intensive care unit. This practice-based study explored the relationship between the predicted PK parameter, the ratio of the area under the concentration-time curve to the 24 h of dosing/minimum inhibitory concentration (AUC 0–24 /MIC or AUIC), and the clinical and microbiological outcomes in critically ill patients with pneumonia due to MDR bacteria. We conducted a prospective cohort study of the treatment of pneumonia due to MDR bacteria in an intensive care unit. The study patients were recruited and assigned to either TGC standard dose (SD, 50 mg q12 h) or high dose (HD, 100 mg q12 h) for the treatment of pneumonia due to MDR bacteria depending on the doctors' decisions. The relationships between the PK/PD parameters and outcomes were examined. Over the study period, 105 patients were included in the study. Whereas C1/2, Cmin, MIC and AUC were dramatically higher in the HD group than in the SD group (all P < 0.05), the Cmax and AUIC had no difference in both groups (all P > 0.05). The patients in the HD group had a higher clinical cure rate than those in the SD group (P = 0.029), but the bacterial eradication rate and survival rate of the patients in the HD group were not better than those in SD group (P = 0.279 and 0.416, respectively). The Cmax, C1/2, Cmin and AUC in the cured group were higher than those in failure group (all P < 0.05). The MICs were dramatically higher in the failure group than those in cure group (P = 0.0001), which led to significantly lower AUICs (P = 0.0001). In the ROC analysis, the areas of Cmax, C1/2, Cmin, AUC, negative-MIC and AUIC under the ROC curve were 0.64, 0.69, 0.67, 0.66, 0.73 and 0.82, respectively. The sensitivity was ascertained to be 75% and the specificity was 89% when the AUIC cut-off value was considered to be 10.12. Moreover, the sensitivity was ascertained to be 63% and the specificity was 80% when the MIC cut-off value was considered to be 1.75 mg/L. The AUIC and MIC are associated with tigecycline treatment outcomes in pneumonia due to MDR bacteria, and aiming to achieve an individualized AUIC ≥ 10.12 when MIC < 1.75 mg/L could improve outcomes. [ABSTRACT FROM AUTHOR]

Highlights • Tigecycline was prescribed as for an 'off label' indication in 91% children. • Clinical success was reported in 86% of the patients. • No serious adverse effects of tigecycline were detected in the patients. Abstract Objective The aim of this study was to evaluate the efficacy and safety of salvage therapy of tigecycline in critically ill children with infections caused by multidrug-resistant (MDR)/extensively drug-resistant (XDR) bacteria after surgery. Methods A retrospective chart review was performed of critically ill children after surgery who had received tigecycline for ≥3 days between June 2012 and May 2016 in the surgical intensive care unit of a tertiary level children's hospital. Results Of 6442 consecutive children admitted after surgery, a total of 22 were enrolled. They had a median age of 7.5 months (interquartile range (IQR), 6 months to 4 years) and a median weight of 7.3 kg (IQR, 5.1–12.5 kg). Patients received tigecycline for a median 17 days (IQR, 12–20 days). The median intensive care unit stay was 56 days (IQR, 38–61 days) and median hospital stay was 78 days (IQR, 61–94 days). Tigecycline was prescribed as culture-directed therapy in 91% of patients and as empirical therapy in 9%. Clinical success was reported in 86% of the patients. The all-cause mortality in this cohort was 18%. No serious adverse effects of tigecycline were detected in these patients. Conclusions Tigecycline salvage therapy was successful in 86% of critically ill pediatric patients with MDR/XDR infections after surgery, with no severe adverse effects. [ABSTRACT FROM AUTHOR]

Introduction During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp , including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia. Methods The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4 μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia. Results Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (<50%). Multivariate analysis showed that recent exposure to corticosteroids (minimum 20 mg per day for more than 5 days within 2 weeks) (adjusted odds ratio (OR) 2.887, 95% confidence interval (CI) 1.170–7.126) and carbapenems (within 2 weeks) (adjusted OR 4.437, 95% CI 1.970–9.991) were significantly associated with tigecycline non-susceptible Acinetobacter bacteremia. Although prior exposure to tigecycline was more common in the case group than in the control group (9.8%, 6/61 vs. 2.2%, 2/91; p = 0.046), this variable was found not to be a significant factor associated with tigecycline non-susceptibility after adjustment for other variables (adjusted OR 1.884, 95% CI 0.298–11.920; p = 0.501). Conclusions These data suggest that tigecycline non-susceptible Acinetobacter spp have emerged and disseminated in the hospital in association with a recent exposure to carbapenems and an immunosuppressed state. This indicates that the rational use of antibiotics through a comprehensive antimicrobial stewardship program, especially in immunosuppressed patients, may be essential in limiting the emergence and spread of multidrug-resistant organisms such as tigecycline-resistant Acinetobacter spp , which are difficult to treat. [ABSTRACT FROM AUTHOR]

Summary The successful use of tigecycline in a 12-month old liver transplant recipient with extensively drug-resistant Acinetobacter baumannii bacteremia is presented. Tigecycline serum concentrations were monitored to help improve antibiotic efficacy and minimize side effects. A literature review identified 11 additional pediatric cases of A. baumannii infection treated with tigecycline since 2011. Tigecycline treatment should be considered in children with extensively drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Summary Objectives Infections with Vibrio vulnificus are commonly fatal, and the speed and accuracy of diagnosis and treatment is directly linked to mortality. The main aims of this study were to investigate the clinical characteristics of six patients with V. vulnificus infections retrospectively and to determine the effect of treatment with tigecycline (TGC) alone compared with doxycycline plus ceftazidime (DOX/CAZ). Methods The medical records of patients were reviewed. The species-specific and pathogenic gene markers were detected by PCR, and multilocus sequence typing (MLST) was performed. Furthermore, the effects of TGC and of DOX/CAZ were determined using time–kill assays. Results MLST revealed six different sequence types and five of them were novel. The complete clinical pattern ( vcg type C , CPS operon allele 1, 16S-rRNA type B ) was found in one strain and the others had a mixed pattern. The lesion was mainly located at the distal end of the extremities and the most common clinical symptoms were fever, pain, erythema, and local swelling. The in vitro time–kill assay indicated that TGC monotherapy at a concentration of 0.1 mg/l had a rapid bactericidal effect against the six tested V. vulnificus strains at 24 h. Conclusions TGC alone might be a better potential therapeutic option than the traditional combination of DOX/CAZ against V. vulnificus . [ABSTRACT FROM AUTHOR]

Summary Background As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) we report antimicrobial resistance among Gram-positive and Gram-negative isolates collected globally from integumentary sources between 2010 and 2014. Methods Minimum inhibitory concentrations and antimicrobial resistance were determined according to Clinical and Laboratory Standards Institute guidelines (US Food and Drug Administration breakpoints against tigecycline). The Cochran–Armitage trend test was used to identify statistically significant changes in resistance. Results Global rates of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii were 38% and 43%, respectively. No S. aureus isolates were resistant to linezolid or vancomycin; all isolates were susceptible to tigecycline. Two percent of Enterococcus faecalis and 28% of Enterococcus faecium were vancomycin-resistant. Extended-spectrum β-lactamase (ESBL) producers accounted for 22% of Klebsiella pneumoniae and 16% of Escherichia coli . Resistance to minocycline among E. faecalis , E. faecium , K. pneumoniae , and E. coli decreased significantly ( p < 0.0001). There were significant increases ( p < 0.0001) in A. baumannii resistance to cefepime, ceftazidime, ceftriaxone, levofloxacin, meropenem, and piperacillin–tazobactam. Conclusions Among isolates from integumentary sources, rates of MRSA and ESBL-producing Enterobacteriaceae are stabilizing. Carbapenems and tigecycline have retained their in vitro activity against Gram-positive and Gram-negative organisms. Few agents were active against A. baumannii ; its increasing resistance is cause for concern. [ABSTRACT FROM AUTHOR]

Highlights • Mycobacterium abscessus is a rare but known causative pathogen of chronic otitis media in children. • Tigecycline can be an acceptable option in the treatment of M. abscessus chronic otitis media. • Emesis from tigecycline can be controlled well with the use of ondansetron. Abstract Mycobacterium abscessus is one of the most pathogenic and chemotherapy-resistant rapidly growing mycobacteria. This Mycobacterium should always be considered as a possible cause of chronic otitis media in children, and treatment might be challenging because of its resistance to multiple antibiotics. There are no reports describing the therapeutic use of tigecycline for the treatment of chronic otitis media caused by M. abscessus. A 10-year-old boy was referred to Tokyo Metropolitan Children’s Medical Center with a 7-year history of recurrent otitis media despite treatment with antibiotics and ventilation tubes. Cultures of the otorrhea yielded Mycobacterium abscessus spp. massiliense , and it showed multiple and high-level resistance. The boy required surgery and underwent initial treatment with clarithromycin, amikacin, and tigecycline for 4 weeks. He experienced emesis as a side-effect of tigecycline, which was well controlled with ondansetron. He was treated successfully with 3 months of subsequent oral clarithromycin and linezolid. This is the first pediatric case of chronic otitis media caused by M. abscessus treated with a tigecycline-containing regimen. Although the therapeutic use of tigecycline remains controversial, especially in the pediatric population, it can be an acceptable option in the treatment of chronic otitis media caused by M. abscessus. [ABSTRACT FROM AUTHOR]

Summary Objectives To assess the efficacy and safety of tigecycline in comparison with other antimicrobial treatments for infectious diseases. Design Databases of PubMed, Embase and the Cochrane Library were searched through Feb. 2015. The reference lists of the initially identified articles and systemic review articles were manually searched. Randomized controlled trials assessing tigecycline and other antibiotics for infectious diseases in adult patients were included. Results Fifteen RCTs including 7689 cases were identified. We found that tigecycline was not as effective as the comparator agents for clinical treatment success (for the clinically evaluable population, odds ratio [OR] = 0.83, 95% confidence interval [CI] = (0.73, 0.96), P=0.01; for the clinically modified intent-to-treat (mITT) population, OR = 0.81, 95% CI = (0.72, 0.92), P=0.001). There was no significant difference in microbiological treatment success with lower eradication rate in tigecycline versus comparators (for the microbiologically evaluable population, OR = 0.94, 95% CI = (0.77, 1.16), P=0.56; for the microbiological mITT populations, OR = 0.91, 95% CI = (0.74, 1.11), P=0.35). Adverse events and all-cause mortality were more common in the tigecycline group. Conclusions Tigecycline is not as effective as other antibiotics with relatively more frequency of adverse events and higher mortality rate. [ABSTRACT FROM AUTHOR]

Summary Objective Clinical treatment for bla KPC -positive Klebsiella pneumoniae isolates is challenging because the recommended antibiotic options are limited and are extraordinarily expensive. This study aimed to explore a new therapy for infection caused by KPC-producing K. pneumoniae . Methods Patients with bla KPC -positive K. pneumoniae infection, were prospectively screened and were categorised into two groups: patients in the study group received a combination-based therapy of cefepime and amoxicillin/clavulanic acid and the control group received tigecycline-based therapy. The pathogen clearance rate, 28-day mortality and cost of the antibiotic treatment were compared between the two groups. Moreover, the checkerboard microdilution method was performed to determine the synergy between cefepime and amoxicillin/clavulanic acid in vitro. Results Twenty-six and 25 cases were enrolled in the study and control groups. The mortality and the overall pathogen clearance rate showed no significant differences ( P =0.311 and P =0.447). Both the total cost and the portion of the cost not covered by insurance were higher for the control group compared to the study group (both P <0.001). Consistently, synergy (65.4%) and partial synergy (26.9%) were the main effects. Conclusions In contrast to the currently recommended tigecycline-based therapy, cefepime and amoxicillin/clavulanic acid combination was an effective and economical option to KPC-KP infection in China. [ABSTRACT FROM AUTHOR]

To investigate the prevalence of ESBL-producing Enterobacteriaceae from blood specimens sent to Microbiology Laboratory RSUP H. Adam Malik and its antibiotic susceptibility pattern to various antibiotics We conducted a retrospective study on blood specimens sent to Microbiology Laboratory RSUP H. Adam Malik, January 2019 - March 2021. The Vitek-2 compact system (bioMerieux®) performed identification and susceptibility testing with Advanced Expert System (AES). In addition, ESBL phenotypic screening was performed with the VITEK 2 compact, which compared the proportion of decreased bacterial growth to cefepime, cefotaxime, and ceftazidime, alone and in the presence of clavulanic acid. We found 1040 isolates from positive blood culture. A total of 333 (32,0%) isolates of Enterobactericeae were identified. From those isolates, there are 60,7% isolates were ESBL-producing Enterobactericeae , consisted of 121 (59,9%) Klebsiella pneumoniae , 76 (37,6%) Escherichia coli , 3(1,5%) isolat Klebsiella oxytoca and 2 (1%). ESBL-producing K.pneumoniae were susceptible to ertapenem (99,2%), meropenem (97,5%), amikacin (95,9%), tigecycline (90,9%), piperacillin-tazobactam (78,5%), cephalosporin (0-60,3%), trimethoprim-sulfamethoxazole (31,4%), ciprofloxacin (25,6%), gentamicin (20,7%), ampicillin sulbactam (19%), aztreonam (4,1%), amoxicillin (0%). ESBL - producing E coli were susceptible to meropenem, ertapenem, amikacin (100%), tigecycline (98,7%), piperacillin-tazobactam (88,2%), gentamicin (53,9%), cephalosporin (0% - 55,3%), ampicillin sulbactam (38,2%), trimethoprim-sulfamethoxazole (22,4%), ciprofloxacin (14,5%), aztreonam (11,8%),amoxicillin(0%). The prevalence of ESBL-producing Enterobacteriaceae from blood specimens, is high and most isolates highly sensitive toward tigecycline, amikacin, meropenem and ertapenem. [ABSTRACT FROM AUTHOR]

Tigecycline is a broad-spectrum antibiotic usually used as a last resort for infections caused by multidrug-resistant and extensively drug-resistant Gram-negative bacteria, such as Enterobacterales and Acinetobacter spp. The evolvement of antimicrobial resistance has led to the increased demand for tigecycline. However, data comparing the efficacy and safety of high (HD) versus standard doses (SD) of tigecycline are limited. Therefore, this study aimed to compare the clinical and microbiological outcomes of these doses in hospitalized patients. This was a retrospective cohort multicenter study. Adult patients admitted between January 2018 and October 2020 who received tigecycline as monotherapy or in combination with other antibiotics for at least 3 days with a microbiologically documented infection were included. Clinical cure was the primary endpoint. Secondary endpoints included microbiological cure, mortality and length of stay. Of 292 patients, 77 were in the HD group while 215 were in the SD group. Baseline characteristics were similar, except for the duration of tigecycline therapy, which was 3 days longer in the HD group (P = 0.007), and source of infection (P <0.0001). Most patients in the HD group had either respiratory (54.5%), skin and soft tissue infections (SSTIs; 22.1%), or more than one site of infections (23.4%). On the other hand, most patients in the SD group had either respiratory (40.4%) or skin and soft tissue infections (40.8%), While microbiological cure was higher in the HD group (16.9% vs. 10.8%; P =0.005), clinical cure rates were lower in the HD group (24.7% vs. 39.1%; P = 0.02). Mortality rate was higher in the HD group at 63.6% compared with 39.1% in the SD group (P <0.0001). Notably, most isolates from patients in the HD group had intermediate susceptibility to tigecycline (51.3%), whereas isolates were mostly susceptible in the SD group (47.9%; P <0.0001). HD regimen of tigecycline in this study was not superior to SD. The less favorable outcomes could be attributed to the lower susceptibility to tigecycline in the HD group. More studies are needed to assess the impact of HD in patients with susceptible isolates. [ABSTRACT FROM AUTHOR]

Summary: Background: The number of reported cases of resistance to tigecycline is increasing. The aim of this study was to evaluate the current standard tigecycline dosage regimen from a pharmacokinetic/pharmacodynamic (PK/PD) perspective. Methods: Pharmacokinetic parameters and microbiological data were analyzed by Monte Carlo simulation in an evaluation of effectiveness. Results: Tigecycline exhibits excellent in vitro antimicrobial activity, however the standard tigecycline dosing regimen fails to achieve the best outcome in vivo for the common drug-resistant strains, including Acinetobacter baumannii, Enterobacter spp, and Klebsiella pneumoniae. This may result in a lack of response to tigecycline therapy or to a further increase in the resistance rate. Conclusions: In the absence of new drugs on the horizon, rather than using a single fixed dosing regimen, tigecycline dosing needs to be optimized in order to achieve the desired successful clinical response and to prevent an escalation in drug resistance. [ABSTRACT FROM AUTHOR]

Summary: Objectives:: To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V+A) in the treatment of complicated skin and skin structure infections (cSSSI). Methods:: A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for ≥5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V+A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting. Results:: A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V+A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V+A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritis, and rash occurred significantly more often in V+A-treated patients. Conclusions:: This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V+A. [Copyright &y& Elsevier]

Summary We describe the case of a 75-year-old woman presenting with spotted fever followed by acute renal failure and septic shock. The infection was caused by Rickettsia typhi , not reported in Calabria district (southern Italy) since World War II. The diagnosis of murine typhus was made 3 days after admission and was based solely on clinical criteria when her worsening condition required a prompt move to the intensive care unit. Therapy with tigecycline was then started immediately and the patient improved dramatically. The diagnosis of murine typhus was confirmed 10 days after admission by immunofluorescence assay. Our case is an example of how the diagnosis of murine typhus is challenging. However, in the case of a disease lacking specific symptoms, clinicians should never forget that, even in geographic areas considered free of flea-borne diseases, the components of the enzootic cycle are present and the diagnosis should never be underestimated. [ABSTRACT FROM AUTHOR]

Summary Limited data suggest that tigecycline may be of value in the treatment of Clostridiumdifficile infection. We reviewed our experience using tigecycline to treat severe c. difficile and compared outcomes to similarly ill patients who did not receive tigecycline. We found no difference between the groups. Further study is needed before tigecycline can be recommended for use in severe C. difficile infection. [ABSTRACT FROM AUTHOR]

Summary: From 2005 to 2009, at Detroit Medical Center, the prevalence of Providencia stuartii increased from 0.52 to 0.91/1000 patient-days (p <0.001). The use of colistin also increased (p <0.001) during the study period. The increase in the prevalence of P. stuartii was associated with an increased use of colistin (p <0.001). Facilities that frequently use colistin and tigecycline should closely monitor the prevalence of P. stuartii along with other Proteeae, since these organisms are intrinsically resistant to colistin and tigecycline. [ABSTRACT FROM AUTHOR]

Summary: Background: This analysis from the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) reports on 24 784 isolates collected from integumentary culture sources between 2004 and 2009. Methods: Minimum inhibitory concentrations (MICs) and susceptibility were determined according to the Clinical and Laboratory Standards Institute guidelines (US Food and Drug Administration breakpoints applied against tigecycline). Results: All methicillin-resistant Staphylococcus aureus were susceptible to tigecycline, linezolid, and vancomycin. MIC90s for tigecycline against Enterococcus faecalis and Enterococcus faecium ranged between 0.12mg/l and 0.25mg/l. Resistance to the carbapenems and tigecycline was low among the Enterobacteriaceae, with resistance at ≤2.0% between 2004 and 2009 for tigecycline against Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter spp, and Serratia marcescens, for imipenem against E. coli and Enterobacter spp, and for meropenem against E. coli, Enterobacter spp, and S. marcescens. Against the Acinetobacter baumannii collected in 2009, resistance to amikacin, ceftazidime, levofloxacin, meropenem, and piperacillin–tazobactam was >30%; between 2004 and 2009 resistance to minocycline varied between 1.4% and 4.8%, and tigecycline MIC90s were ≤2mg/l. Against the Pseudomonas aeruginosa collected, MIC90s were greater than the susceptibility breakpoint for cefepime, ceftazidime, imipenem, levofloxacin, and meropenem. Conclusions: The problem of antimicrobial resistance is demonstrated by the data presented. T.E.S.T. continues to provide valuable information on antimicrobial resistance globally. [ABSTRACT FROM AUTHOR]

Abstract: The treatment of post-surgical meningitis due to multidrug-resistant (MDR) Acinetobacter baumannii is a therapeutic dilemma. The cases of two patients with MDR A. baumannii meningitis secondary to surgical site infections, successfully treated with combination regimens including tigecycline, are presented. [ABSTRACT FROM AUTHOR]

Abstract: We present a case of Rhodococcus equi primary retroperitoneal abscesses without pulmonary involvement in an immunocompromised patient with severe nephrotic syndrome. No risk factors for exposure to R. equi were present. The infection was successfully treated with long-term combination antibiotic treatment including linezolid and tigecycline. [Copyright &y& Elsevier]

Summary: Complicated skin and skin structure infections encompass a diverse range of diseases frequently caused by Gram-positive pathogens, and most commonly by Staphylococcus aureus and Streptococcus pyogenes. Treatment of these infections represents a growing clinical challenge as increases in multi-drug-resistant organisms and cross-resistance to antimicrobial therapy have made empiric therapeutic choices more difficult, particularly for patients with known risk factors or who are immunocompromised. Complicating this issue has been the relative lack of new agents with antimicrobial potency against prevalent resistant species such as meticillin-resistant S. aureus (MRSA). Tigecycline, a novel glycylcycline, is a broad-spectrum antibiotic with potent microbiological activity against the wide variety of organisms implicated in the aetiology of complicated skin and skin structure infections. Recent phase III clinical data confirm previous observations on the safety and efficacy of tigecycline for the treatment of complicated skin and skin structure infections. Tigecycline was shown to be non-inferior to combination vancomycin-aztreonam regimens and exhibited high clinical success rates. MIC90 values for tigecycline were uniformly low for both susceptible and resistant pathogens. Adverse events were similar in incidence for both patient populations, with nausea and vomiting reported more frequently with tigecyclinetreated patients while rash and elevated liver transaminases were most commonly observed in the vancomycin-aztreonam treatment group. Tigecycline helps to address the urgent need for new antimicrobial agents to combat the emergence of multi-drug-resistant Gram-positive pathogens. Current clinical, microbiological and safety data support the use of tigecycline as a valuable therapeutic option in the treatment of complicated skin and skin structure infections. [Copyright &y& Elsevier]