minocycline and Critical-Illness

Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

Topics: Abdominal Cavity; Anti-Bacterial Agents; Candida; Candidiasis; Carbapenems; Critical Illness; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Minocycline; Peritonitis; Practice Guidelines as Topic; Risk Factors; Tigecycline

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Critical Illness; Drug Therapy, Combination; Enterobacteriaceae; Humans; Minocycline; Pneumonia, Bacterial; Survival Analysis; Tigecycline; Urinary Tract Infections

Here we review the effectiveness and safety of high-dose tigecycline (200mg daily). A systematic search was performed in PubMed and Scopus databases as well as of abstracts presented at scientific conferences. Eight studies (263 patients; 58% critically ill) were included, comprising one randomised controlled trial (RCT), four non-randomised cohorts and three case reports. Klebsiella pneumoniae was the most commonly isolated pathogen (reported in seven studies). In the RCT, response in the clinically evaluable patients was 85.0% (17/20) in the 100mg every 12h (q12h) group and 69.6% (16/23) in the 75mg q12h group (P=0.4). More episodes of diarrhoea, treatment-related nausea and vomiting developed in the high-dose group (14.3% vs. 2.8%, 8.6% vs. 2.8% and 5.7% vs. 2.8%, respectively; P>0.05 for all comparisons). Three (8.6%) and 7 (19.6%) patients died in the 200mg and 150mg daily dose groups, respectively. The cohort studies enrolled patients with severe infections, including ventilator-associated pneumonia and complicated intra-abdominal infections. Mortality with high-dose tigecycline (100mg q12h) in the cohort studies ranged from 8.3% to 26%; mortality in the low-dose groups (50mg q12h) ranged from 8% to 61% and depended on the severity of the underlying infection. There are limited available data regarding the effectiveness and safety of high-dose tigecycline. Most of the data come from critically ill patients with difficult-to-treat infections. Pharmacokinetic/pharmacodynamic properties of tigecycline suggest that high-dose regimens may be more effective than low-dose regimens. Candidates for administration of high-dose tigecycline should be also defined.

Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Drug Administration Schedule; Female; Humans; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Survival Analysis; Tigecycline; Treatment Outcome

The spread of multidrug-resistant, extensively drug-resistant and pan-drug-resistant pathogens is causing an unprecedented public health crisis. The limited current therapeutic options led to the revival of two 'old' antibiotics - colistin and fosfomycin - for which a better understanding of their pharmacokinetics in the critically ill patient and in specific body compartments is required. Tigecycline's use in clinical practice for nonapproved indication based on its in vitro activity against problematic pathogens requires caution and probably higher doses. Furthermore, all three antibiotics should be used as part of combination regimens in order to prevent resistance and optimize outcomes. The development of new antibacterials in the near future, namely combinations of avibactam, ceftolozane/tazobactam and plazomicin, seems promising; however, they will only partially address current mechanisms of resistance.

Topics: Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Minocycline; Tigecycline

Infection by Staphylococcus aureus in critically ill patients is usually associated with antimicrobial resistance and high mortality. A more effective antibiotic treatment is needed to replace older drugs that have limited efficacy. Novel substances active on methicillin-resistant Staphylococcus aureus, which are already available on the market or are still in development, are discussed in this review, with emphasis on nosocomial infections.. A number of new antibiotics are on the market (linezolid, quinupristin-dalfopristin, daptomycin) and there is good evidence regarding their efficacy, especially in methicillin-resistant Staphylococcus aureus infections. Linezolid is, to date, the best alternative in treating nosocomial pneumonia by methicillin-resistant Staphylococcus aureus. It is cost-effective; resistance levels are still very low but there are some concerns regarding its adverse events. Quinupristin-dalfopristin shows good activity in vitro but its efficacy in patients with pneumonia by methicillin-resistant Staphylococcus aureus is modest. Daptomycin is not recommended for pulmonary infections because of its reduced penetration in the lung tissue. Under current phase III trials in patients with nosocomial infections are tigecycline, ceftobiprole, and three new glycopeptides, all with particular activity against methicillin-resistant Staphylococcus aureus.. For the moment, there are limited and rather expensive therapeutic options for the infections by Staphylococcus aureus in the critically ill. No dramatic superiority of the new drugs in comparison to the standard therapies was observed in most of the clinical trials. Better results on the efficacy of the drugs under investigation are expected.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Critical Illness; Daptomycin; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Virginiamycin

Topics: Acinetobacter baumannii; Adult; Animals; Anti-Bacterial Agents; Critical Illness; Humans; Microbial Sensitivity Tests; Minocycline

To determine the efficacy of minocycline and rifampin-impregnated catheters compared to non-impregnated catheters in critically ill patients.. Prospective, randomized, double-blind, controlled, multicenter trial.. Intensive care units of seven acute-care teaching hospitals in Spain. PATIENTS. Intensive care unit patients requiring triple-lumen central venous catheter for more than 3 days.. At catheter insertion, 228 patients were randomized to minocycline and rifampin-impregnated catheters and 237 to non-impregnated catheters. Skin, catheter tip, subcutaneous segment, hub cultures, peripheral blood and infusate cultures were performed at catheter withdrawal. The rate of colonization, catheter-related bloodstream infection (CRBSI) and catheter-related clinical infectious complications (purulence at the insertion site or CRBSI) were assessed.. In the intention-to-treat analysis (primary analysis), the episodes per 1000 catheter days of clinical infectious complications decreased from 8.6 to 5.7 (RR =0.67, 95% CI 0.31-1.44), CRBSI from 5.9 to 3.1 (RR =0.53, 95% CI 0.2-1.44) and tip colonization from 24 to 10.4 (RR =0.43, 95% CI 0.26-0.73). Antimicrobial-impregnated catheters were associated with a significant decrease of coagulase-negative staphylococci colonization (RR =0.24, 95% CI 0.13-0.45) and a significant increase of Candida spp. colonization (RR =5.84, 95% CI 1.31-26.1).. The use of antimicrobial-impregnated catheters was associated with a significantly lower rate of coagulase-negative staphylococci colonization and a significant increase in Candida spp. colonization, although a decrease in CRBSI, increase in 30-day survival or reduced length of stay was not observed.

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood-Borne Pathogens; Catheterization, Central Venous; Catheters, Indwelling; Critical Illness; Cross Infection; Double-Blind Method; Drug Delivery Systems; Humans; Intensive Care Units; Minocycline; Prospective Studies; Rifampin; Treatment Outcome

Topics: Anti-Bacterial Agents; Continuous Renal Replacement Therapy; Critical Illness; Humans; Minocycline; Tigecycline

Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse.. A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017.. Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly.. A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed.. The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01).. The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Ciprofloxacin; Comorbidity; Critical Illness; Drug Combinations; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Intensive Care Units, Pediatric; Male; Minocycline; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Sulfadoxine; Trimethoprim

To assess the association of survival and treatment with colistin and tigecycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.. An observational cohort study was carried out. Targeted therapy consisted of monotherapy with colistin (9 million UI/day) or combined therapy with colistin and tigecycline (100 g/day). The primary outcome was 30-day crude mortality. The association between combined targeted therapy and mortality was controlled for empirical therapy with colistin, propensity score of combined therapy and other potential confounding variables in a multivariate Cox regression analysis.. A total of 118 cases were analysed. Seventy-six patients (64%) received monotherapy and 42 patients (36%) received combined therapy. The source of bacteraemia was primary in 18% (21/118) of the patients, ventilator-associated pneumonia in 64% (76/118) and other sources in 14% (16/118). The 30-day crude mortality rate was 62% (42/76) for monotherapy and 57% (24/42) for combined therapy. The variables associated with 30-day crude mortality were: Charlson index (hazard ratio (HR) 1.16, 95% CI 1.02-1.32; p 0.028), empirical therapy with colistin (HR 2.25, 95% CI 1.33-3.80; p 0.003) and renal dysfunction before treatment (HR 1.91, 95% CI 1.01-3.61; p 0.045). Combined targeted therapy was not associated with lower adjusted 30-day crude mortality (adjusted HR 1.29, 95% CI 0.64-2.58; p 0.494).. Combined targeted therapy with high-dose colistin and standard dose tigecycline was not associated with lower crude mortality of bacteraemia due to carbapenem-resistant A. baumannii in critically ill patients.. Registered in ClinicalTrials.gov. Identifier: NCT02573064.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Bacteremia; Carbapenems; Cohort Studies; Colistin; Critical Illness; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Propensity Score; Survival Analysis; Tigecycline; Treatment Outcome

Nonclinical studies have suggested that oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coadministration of CST with MIN (CST-MIN) may reduce the incidence of acute renal failure as well as produce additive or synergistic antimicrobial effects. A multicenter retrospective cohort study was conducted using the Premier Research database to examine the impact of CST-MIN on acute renal failure. Inclusion criteria were as follows: age of ≥18 years, intensive care unit admission at CST initiation, primary International Classification of Diseases 9 (ICD-9) diagnosis of pneumonia or sepsis, nondialysis at hospital admission, and discharge between January 2010 and December 2015. ICD-9 code 584.XX or ICD-10 code N17 was used to define acute renal failure. Baseline comparisons, 1:8 propensity score matching, and confirmatory logistic regression analyses were conducted. In total, 4,817 patients received CST and met inclusion criteria; 93 received CST-MIN. Unadjusted frequency of acute renal failure was significantly lower in patients receiving CST-MIN than CST (11.8% versus 23.7%,

Topics: Acute Kidney Injury; Adult; Aged; Cohort Studies; Colistin; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Minocycline; Patient Readmission; Protective Agents; Retrospective Studies; Treatment Outcome

Topics: Acute Kidney Injury; Colistin; Critical Illness; Humans; Minocycline; Retrospective Studies

The objective of this study was to assess the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem (MEM) in critically-ill patients with bloodstream infections (BSI) due to Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) with MEM minimum inhibitory concentrations (MICs) ≥16 mg/L. Nineteen critically-ill patients with KPC-Kp BSI were given combination therapy including MEM, tigecycline, plus colistin or gentamicin (according to susceptibility testing). MEM was administered as an extended 3-hour infusion of 2 g every 8 hours, or adjusted according to renal function. MEM plasma concentrations were determined by high-performance liquid chromatography. PK/PD targets for MEM were defined as T > 40% 1×MIC and T > 40% 4×MIC. Possible synergisms between MEM and coadministered agents were assessed by time-kill assays based on plasma levels for MEM and on fixed plasma concentrations for the other agents. In none of 19 patients MEM reached any PK/PD target. The actual MEM MICs were 256, 512, and 1024 mg/L in 1, 3, and 15 isolates, respectively. However, theoretically, the PK/PD target of T > 40% 1×MIC could have been achieved in 95%, 68%, 32% and 0% of the isolates for MIC equal to 8, 16, 32, and 64 mg/L, respectively. No synergisms were observed between MEM and coadministered agents. In conclusion, high-dose MEM failed to reach PK/PD targets in 19 patients with BSI due to KPC-Kp with very high MEM MICs. On a theoretical basis, our results suggest a possible usefulness of MEM against resistant blood isolates with MICs up to 32 mg/L.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Synergism; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline

To evaluate the efficacy of tigecycline for treatment of ventilator-associated pneumonia in critically ill elderly patients.. Data of critically ill elderly patients with ventilator-associated pneumonia treated with tigecycline in the intensive care unit was collected from June 2011 to March 2014 in this retrospective study, to evaluated the clinical efficacy of tigecycline.. A total of 79 patients (83.5% male) were included, the mean age was 84 years old (rang, 65 years to 100 years old). Acinetobacter baumannii (39.1%), Pseudomonas aeruginosa (35.0%) and Klebsiella pneumonia (23.8%) were the most common pathogens.All patients were treated with tigecycline, 54.4% combined with other antimicrobial agents, 35.4% treated with double dose of tigecycline, and the mean course of antibiotic treatment was 9 days (range, 2 days to 22 days). After treatment, clinical success were recorded in 44 patients (55.7%), clinical failure were recorded in 29 patients, clinical uncertainty were recorded in 6 patients.28 days after treatment, patients' overall mortality was 39.0%.The clinical success rates were associated with acute physiology and chronic health evaluation (APACHE) Ⅱ score less than 15 (the clinical success rates were 72.2% and 41.9% in patients with APACHE Ⅱ score<15 and APACHE Ⅱ score≥15, respectively; P=0.007); treated with double dose of tigecycline (71.4% vs 47.1%, P=0.037) or combination regimens were also had significant difference (67.4% vs 41.7%, P=0.022).. Treatment of tigecycline combined with other antimicrobial agents and double dose of tigecycline may both can improve clinical efficacy in critically ill elderly patients with ventilator-associated pneumonia.

Topics: Acinetobacter baumannii; Aged; Aged, 80 and over; APACHE; Critical Illness; Female; Humans; Intensive Care Units; Male; Minocycline; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Retrospective Studies; Tigecycline

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Blood Coagulation Disorders; Critical Illness; Female; Fibrinogen; Humans; Male; Middle Aged; Minocycline; Partial Thromboplastin Time; Tigecycline

Topics: Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Enterocolitis, Pseudomembranous; Humans; Male; Minocycline; Tigecycline

Based on tigecycline linear pharmacokinetic/pharmacodynamics, dose increases have been advocated to maximise activity especially when severe infections with high bacterial load and/or multidrug resistance are suspected. This practice-based observational study explored factors associated with tigecycline administration (100 mg/12h, 200 mg loading dose) in severely ill patients with complicated intra-abdominal infection (cIAI) admitted to four Surgical Critical Care Units (SCCUs).. Medical records of all consecutive adult patients with cIAI and controlled infection source requiring surgery and admission for ≥ 48 h to SCCU were reviewed and divided into patients treated with a regimen including tigecycline (tigecycline group) and those that not (control group). A logistic regression model was performed using "tigecycline administration" (dependent variable) and variables showing differences (p ≤ 0.1) in bivariate analyses (independent variables).. One hundred and twenty one patients were included. In the tigecycline group, higher percentage of patients (vs. controls) presented colon as surgical site (66.7% vs. 41.8%, p = 0.006), nosocomial infection (55.6% vs. 26.9%, p = 0.001), mechanical ventilation (48.1% vs. 28.4%, p = 0.025), chronic renal replacement therapy (40.7% vs. 19.4%, p =0.008), septic shock (72.2% vs. 46.3%, p = 0.004), and higher values of SAPS II (48.0 ± 15.0 vs. 39.6 ± 15.5, p = 0.003), SOFA at admission (7.0 ± 3.3 vs. 5.5 ± 3.7, p = 0.020), lactate-24h (2.5 ± 2.8 vs. 1.6 ± 0.9, p = 0.029) and CRP-72 h (207.4 ± 87.9 vs. 163.7 ± 76.8, p = 0.021). In the multivariate analysis (R2 = 0.187, p < 0.001) nosocomial infection (OR = 7.721; 95%CI = 2.193, 27.179; p = 0.001), colon as infection site (OR = 4.338; 95%CI = 1.432, 13.145; p = 0.009) and CRP-72 h (OR = 1.009 per-unit; 95%CI = 1.002, 1.016; p = 0.012) were associated with tigecycline administration.. In severely ill patients with cIAI, high-dose tigecycline administration was associated with nosocomial origin of cIAI and colon as source infection site.

Topics: Aged; Anti-Bacterial Agents; Critical Care; Critical Illness; Digestive System Surgical Procedures; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Peritonitis; Postoperative Complications; Prospective Studies; Retrospective Studies; Surgical Wound Infection; Tigecycline

Topics: Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Severity of Illness Index

Necrotizing skin and soft tissue infections (NSTI) form a group of aggressive diseases that require radical debridement for infection control. Simultaneously, a high-dose broad spectrum antibiotic regimen needs to be initiated with control of septic complications in the intensive care setting. The aim of this work is to analyze the efficacy and safety of tigecycline in a subpopulation of hospitalized, severely ill surgical NSTI patients who were documented in a large multicenter non-interventional study on tigecycline use in routine clinical practice.. A total of 1,025 patients with severe infections including complicated skin and soft-tissue infections (cSSTI, n=163; 15,9%) were enrolled in a prospective multi-center non-interventional study. Patients were to receive an initial intravenous dose of 100 mg tigecycline, followed by 50 mg twice daily. Prospectively documented parameters included clinical findings, APACHE II score, microbiological and standard laboratory assessments, surgical measures, and clinical outcomes including adverse events.. Of 163 patients were treated for cSSTI, with the largest subgroup being NSTI patients (n=50, 30.7% of all cSSTI, mean age 61 y, median APACHE II score 20). Forty-eight NSTI patients (96%) had at least one comorbidity. In 80% of patients, the treatment was started after previous antibiotic treatment had failed and in 34% resistant pathogens were isolated (28% methicillin resistant Staphyloccocus aureus [MRSA], 4% extended-spectrum-beta-lactamase (ESBL)-producing bacteria, and 2% vancomycin-resistant Enterococci (VRE). Tigecycline was administered as a single agent in 32 patients; 17 received combination regimens. Data from one patient were not reported. Rates of clinical cure or improvement with tigecycline treatment were 90.2%. Two patients (4%) had drug related adverse events (one thrombocytopenia and one fever/chills); 10 patients (20%) died.. Tigecycline alone or in combination therapy was an effective and safe antibiotic treatment in critically ill and antimicrobially pre-treated patients with NSTI frequently caused by resistant pathogens.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tigecycline; Treatment Outcome

The aim of this study was to assess the efficacy of tigecycline in the treatment of infections due to carbapenemase-producing Klebsiella pneumoniae (CPKP) in critically ill patients.. A retrospective observational study was conducted in critically ill patients receiving different tigecycline doses for severe CPKP infections. We evaluated demographic data, localization and severity of infection, response to therapy, and mortality.. Fifteen patients received tigecycline for 16 episodes of CPKP infection. The main infections were pneumonia (31%), urinary tract infection (31%), peritonitis (20%), catheter-related bacteraemia (12%), and meningitis (6%). Most infections were complicated with severe sepsis (44%), septic shock (12%), and/or bacteraemia (19%). The daily maintenance dose of tigecycline was 200 mg in 10 episodes and 100 mg in 6 episodes. The overall 30-day mortality rate was 25%. Univariate analysis showed that mortality was significantly associated (p < 0.01) with mean APACHE II and SOFA scores and the presence of immunosuppression, but not with the tigecycline dose.. Tigecycline appears to be an effective therapy for severe infections due to CPKP in critically ill patients. Mortality is related to the severity of the underlying disease. We observed no benefit from a higher maintenance dose of tigecycline, although the number of patients included in the study was too small to draw any general conclusions in this regard.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline

This prospective observational study aimed at describing prescription patterns of tigecycline and patient outcomes in 26 French intensive care units (ICU).. Data of consecutive cases of adult patients treated with tigecycline were collected from the initiation until 7 days after the end of treatment. Response to treatment was classified as success, failure or undetermined and analyses were presented according to severity (SOFA score <7 or ≥7). Survival was recorded at 28 days.. A total of 156 patients were included (64% male, age 60 ± 15 years). At inclusion, 53% had a SOFA score ≥7; 93% had received prior anti-infective agents. Tigecycline was given as first-line treatment in 47% of patients, mostly in combination (67%), for intra-abdominal (IAI 56%), skin and soft tissue (SSTI 19%) or other infections. A total of 76% of the treated infections were hospital-acquired. Bacteraemia was reported in 12% of patients. Median treatment duration was 9 days. Tigecycline was prematurely stopped in 42% patients. The global success rate was 60% at the end of treatment, and significantly higher with treatment duration more than 9 days (76 vs. 47%, P < 0.001). Success rate was 65% for patients alive at the end of treatment. Success rates tended to decrease with illness severity, immunosuppression, bacteraemia and obesity. Survival rate at day 28 was 85% in the whole cohort and significantly higher in the less severely ill patients (P < 0.001).. Tigecycline success rates appear comparable to those reported in clinical studies in ICU with severe infections. Tigecycline could be an alternative in ICU patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Critical Illness; Cross Infection; Drug Therapy, Combination; Female; France; Hospital Mortality; Humans; Immunocompromised Host; Infections; Intensive Care Units; Male; Middle Aged; Minocycline; Multivariate Analysis; Obesity; Patient Outcome Assessment; Prospective Studies; Severity of Illness Index; Tigecycline; Young Adult

Topics: Anti-Bacterial Agents; Critical Illness; Female; Hospital Mortality; Humans; Infections; Male; Minocycline; Tigecycline

The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses.. We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated.. Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure.. TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Prospective Studies; Retrospective Studies; Severity of Illness Index; Tigecycline

Few antimicrobials are currently active to treat infections caused by extremely resistant Gram-negative bacilli (ERGNB), which represent a serious global public health concern. Tigecycline, which covers the majority of these ERGNB (with the exception of Pseudomonas aeruginosa), is not currently approved for hospital-acquired pneumonia, and several meta-analyses have suggested an increased risk of death in patients receiving this antibiotic. Other studies suggest that the use of high-dose tigecycline may represent an alternative in daily practice. De Pascale and colleagues report that the clinical cure rate in patients with ventilator-associated pneumonia is significantly higher with a high dose of tigecycline than with the conventional dose, although mortality was unaffected. This high dose is safe; no patients required discontinuation or dose reduction.

Topics: Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Severity of Illness Index

Intra-abdominal infection (IAI) is a frequent complication found in surgical intensive care unit (SICU) and continues to be associated with considerable mortality. Tigecycline, the first-in-class glycylcycline has demonstrated a broad spectrum of activity against a wide range of bacteria commonly found in IAI. This observational retrospective study aimed to describe the experience with tigecycline for serious nosocomial IAI in the SICU. Data were collected from 23 consecutive patients admitted to SICU with serious nococomial IAI who had received empirical treatment with tigecycline. In all cases, IAI was diagnosed via emergency surgery. Severe sepsis was found in 56.5% and 43.5% developed septic shock. Oncological disease was the most common comorbidity (60%). The mean Simplified Acute Physiology Score (SAPS) III within 24 hours from IAI diagnosis was 57.5±14.7, and 87% showed a McCabe score >1 (2 or 3). Escherichia coli was the most common pathogen (43.5%), followed by Bacteroides spp. and Streptococcus spp. (30.4%, respectively). All but one patient received tigecycline in combination (95.7%), particularly with fluconazole (52.2%), followed by piperacillin-tazobactam (43.5%). Empirical antibiotic therapy was considered adequate in 95%. The mean duration of treatment was 8.5±4.5 days. A favorable response was achieved in 78%. Failure of the antibiotic therapy was not observed in any patient. None of the patients discontinued tigecycline due to adverse reactions. SICU mortality was 13%, with no deaths attributable to tigecycline. These findings suggest that tigecycline combination therapy is an effective and well tolerated empirical treatment of serious nosocomial IAI in the SICU.

Topics: Adult; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Critical Care; Critical Illness; Cross Infection; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Postoperative Complications; Retrospective Studies; Sepsis; Shock, Septic; Tigecycline; Treatment Outcome

It is being increasingly recognised by clinicians and scientists that participants in randomised clinical trials (RCTs) of antibiotics of last resort do not represent the patients who will later be treated with these drugs. Data on this subject are limited and have not been investigated systematically. This observational study aimed to examine this hypothesis quantitatively, using the example of tigecycline. To evaluate the influence of recruitment, patients eligible for clinical trials were retrospectively compared with ineligible patients regarding baseline and clinical characteristics as well as outcome parameters, e.g. length of hospital stay, intensive care unit (ICU) stay, ventilation and mortality. The clinical characteristics of 187 patients illustrated differences in the nature and severity of disease, co-morbidities and outcome. Eligible and ineligible patients differed in a number of parameters, e.g. median APACHE II score (15.5 vs. 28.0), number of liver transplantations (5% vs. 18%; P=0.048), septic shock (21% vs. 49%; P=0.001), need for mechanical ventilation (30% vs. 79%; P<0.001), mean length of ICU stay (19.3 days vs. 40.7 days) and death (19% vs. 46%; P=0.001). Critically ill patients were under-represented in clinical trials. Moreover, only a minority of patients in clinical practice (13%) were potentially eligible for a pivotal RCT. The disparities likely result from strict exclusion criteria in RCTs and recruitment bias. These data emphasise the importance of including critically ill patients in RCTs of antibiotics against multiresistant bacteria in order to account for those who will later be treated.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Female; Humans; Male; Middle Aged; Minocycline; Patient Selection; Randomized Controlled Trials as Topic; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Blood; Critical Illness; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; India; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and skin and skin structure infections and community-acquired bacterial pneumonia. Notwithstanding this, the tigecycline's pharmacological and microbiological profile encourage physicians' use of the drug in other infections. The aim of this study was to characterize the indications type, pathogens, and outcomes of patients who were treated with tigecycline. We analyzed the tigecycline prescriptions in 209 patients in 23 Latin American centres using an electronic form included in the website LatinUser (http://www.clinicalrec.com.ar). Sixty-six patients (31.5%) received tigecycline for approved indications, and 143 (68.5%) for "off label" indications (47% with scientific support and 21.5% with limited or without any scientific support). The most frequent "off label" use was ventilator-associated pneumonia (VAP) (76 patients). The etiology of infections was established in 88 patients (42%). Acinetobacter spp. (54.5%, in 65% of cases carbapenems-resistant), methicillin-resistant Staphylococcus aureus (12%), and extended spectrum β-lactamases-producing Enterobacteriaceae (10%) were the most common microorganisms isolated. Overall, attending physicians reported clinical success in 144 of the 209 patients (69%). Global mortality proportion was 35,5% (74/209 patients). Our study shows that the off label use of tigecycline is frequent, especially in VAP due to multidrug-resistant pathogens, where the therapeutic options are limited (eg: carbapenems-resistant Acinetobacter spp.). Physicians must evaluate the benefits/risks to use this antibiotic for indications that lack rigorous scientific support.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Child; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Internet; Male; Middle Aged; Minocycline; Off-Label Use; Pneumonia, Ventilator-Associated; Practice Patterns, Physicians'; Registries; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

Tigecycline was approved for the treatment of complicated intra-abdominal and complicated skin/skin structure infections. Because of its in vitro effectiveness for multidrug-resistant (MDR) isolates, tigecycline has been prescribed more broadly. This study evaluated tigecycline use after its first introduction in Taiwan and experience with tigecycline for the treatment of MDR Acinetobacter baumannii (MDRAB) infection, especially for ventilator-associated pneumonia.. Patients treated with tigecycline were collected retrospectively from February 2008 to July 2008 in Taipei Veterans General Hospital, a 2,900-bed tertiary care medical center in Taiwan. Patients were divided into three groups according to the indications: Group 1, Food and Drug Administration-approved indications; Group 2, health care-associated pneumonia (HAP); and Group 3, urinary tract infection, osteomyelitis, bacteremia, etc. Cases of MDRAB were also identified.. Among 66 cases, indications for the administration of tigecycline included Food and Drug Administration-approved indications (12, 18.2%), HAP (38, 57.6%), bacteremia (3, 4.5%), catheter-related infections (3, 4.5%), urinary tract infection (4, 6.1%), osteomyelitis (4, 6.1%), and others (2, 3%). Clinical outcome was positive in 20 cases, with higher clinical success rate for Group 1 than Group 2, which may correlate with higher Sequential Organ Failure Assessment score, older age, and more frequent intensive care admission in Group 2. Of the microbiologically evaluable cases, MDRAB predominated (33/51, 64.7%). Among infections with MDRAB (excluding pneumonia without ventilator), the clinical success rate was 12% (3/25).. The most common indication for the prescription of tigecycline was HAP. Success rate for MDRAB infection was lower than that previously reported, possibly because of serious underlying conditions and comorbidities in our patients. Because of limited choices, physicians should weigh the risk and benefit for prescribing tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Humans; Middle Aged; Minocycline; Off-Label Use; Pneumonia, Ventilator-Associated; Retrospective Studies; Taiwan; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carrier State; Critical Illness; Disease Outbreaks; Drug Resistance, Bacterial; Humans; Incidence; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is a novel antimicrobial agent recently licensed in the United Kingdom (UK), United States and Europe. It is a broad spectrum glycylcycline antibiotic which has structural similarities to the tetracyclines but is more potent against tetracycline-resistant organisms. It is only available as an intravenous (IV) preparation. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of tigecycline. The article also discusses the warnings and precautions associated with the use of this drug. Tigecycline may be used for complicated intra-abdominal and complicated skin and soft tissue infections. It is also likely to find a role in the treatment of infections caused by multi-resistant organisms such as Acinetobacter species.

Topics: Anti-Bacterial Agents; Bacterial Infections; Critical Care; Critical Illness; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Europe; Humans; Microbial Sensitivity Tests; Minocycline; Patient Selection; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; United Kingdom; United States

Topics: Actinobacteria; Aged; Anti-Bacterial Agents; Critical Illness; Female; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Tigecycline

To describe the peritoneal fluid penetration of tigecycline.. A 33-year-old critically ill man who had undergone orthotopic liver and cadaveric renal transplant presented with sepsis. The patient required empiric antimicrobial coverage, continuous veno-venous hemofiltration, prolonged mechanical ventilation, tracheostomy placement, and maintenance immunosuppressive therapy. After multiple infections with multi-drug resistant pathogens, the patient developed vancomycin-resistant Enterococcus faecium peritonitis. Tigecycline 50 mg was administered every 12 hours, and ascites fluid drug concentrations were obtained. Drug concentrations in the peritoneal fluid were determined by high-performance liquid chromatography and revealed a tigecycline concentration of 0.074 microg/mL. Despite aggressive measures, the patient's condition continued to decline; he died 2 weeks after tigecycline initiation.. As of October 3, 2006, these are the first data to describe tigecycline peritoneal fluid penetration. Tigecycline was aggressively administered at twice the recommended dosage for overt liver failure in light of the severity of this patient's condition. A tigecycline peritoneal fluid concentration of 44-54% of serum concentration was calculated based on the patient's peritoneal fluid drug concentration and previously published serum concentrations from a similar population.. Peritoneal penetration of tigecycline was approximately 50% in this critically ill patient. Establishment of site-specific breakpoints for tigecycline may be necessary. Future studies will need to evaluate the penetration of tigecycline into peritoneal fluid and other tissues.

Topics: Adult; Ascitic Fluid; Critical Illness; Drug Resistance, Multiple, Bacterial; Fatal Outcome; Humans; Male; Minocycline; Permeability; Tigecycline

To report the use of tetracyclines for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).. Observational case series.. . The Presley Regional Trauma Center located within the Regional Medical Center, Memphis, Tennessee, USA.. Seven critically ill trauma patients with VAP caused by A. baumannii isolates that were resistant to all antibiotics tested except for doxycycline or minocycline.. Patients were treated with IV doxycycline or minocycline for an average of 13.5 (range 9-20) days.. Doxycycline or minocycline was successful in six of seven patients.. Doxycycline or minocycline may be effective for treating multidrug-resistant A. baumannii VAP.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; APACHE; Bronchoalveolar Lavage Fluid; Critical Care; Critical Illness; Cross Infection; Doxycycline; Drug Resistance, Multiple, Bacterial; Humans; Infection Control; Infusions, Intravenous; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiration, Artificial; Retrospective Studies; Tennessee; Trauma Centers; Treatment Outcome