minocycline and Bacteremia

Patients with bloodstream infections (BSI) are associated with high mortality rates. Due to tigecycline has shown excellent in vitro activity against most pathogens, tigecycline is selected as one of the candidate drugs for the treatment of multidrug-resistant organisms infections. The purpose of this study was to evaluate the effectiveness and safety of the use of tigecycline for the treatment of patients with BSI. The PubMed and Embase databases were systematically searched, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. The primary outcome was mortality, and the secondary outcomes were the rate of clinical cure and microbiological success. 24 controlled studies were included in this systematic review. All-cause mortality was lower with tigecycline than with control antibiotic agents, but the difference was not significant (OR 0.85, [95% confidence interval (CI) 0.31-2.33; P = 0.745]). Clinical cure was significantly higher with tigecycline groups (OR 1.76, [95% CI 1.26-2.45; P = 0.001]). Eradication efficiency did not differ between tigecycline and control regimens, but the sample size for these comparisons was small. Subgroup analyses showed good clinical cure result in bacteremia patients with CAP. Tigecycline monotherapy was associated with a OR of 2.73 (95% CI 1.53-4.87) for mortality compared with tigecycline combination therapy (6 studies; 250 patients), without heterogeneity. Five studies reporting on 398 patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae BSI showed significantly lower mortality in the tigecycline arm than in the control arm. The combined treatment with tigecycline may be considered the optimal option for severely ill patients with BSI.

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Minocycline; Survival Analysis; Tigecycline; Treatment Outcome

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).. Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Pneumonia; Polymyxin B; Polymyxins; Tigecycline; Treatment Outcome; Urinary Tract Infections

Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases.. We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed.. In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009).. Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Minocycline; Respiratory Tract Infections; Retrospective Studies; Tigecycline; Treatment Outcome

Multidrug-resistant (MDR) Acinetobacter baumannii infections have emerged as a serious threat worldwide. As novel agents have yet to be developed, understanding the effectiveness and safety of older antibiotics has become a priority. The purpose of this systematic review was to summarise the available clinical evidence on the use of tetracyclines for the treatment of A. baumannii infections. Ten retrospective studies regarding doxycycline and minocycline for the treatment of 185 A. baumannii infections (of which 65.4% were respiratory infections and 13% were bloodstream infections) in 156 patients were available. In most cases (86.4%), tetracyclines were administered in combination with another agent. The usual dosage of doxycycline or minocycline was 100mg intravenous or per os twice daily (usually with a 200mg loading dose for minocycline). Clinical success was achieved in 120 (76.9%) of 156 patients; in 87 (71.9%) of 121 respiratory infections and in 21 (87.5%) of 24 bloodstream infections. Twenty-two deaths occurred in 100 recorded cases. Microbiological eradication was attained in 72 (71.3%) of 101 available cases and documented microbiological eradication was reached in 59 (66.3%) of 89 available cases. Adverse events were noted in only 1 of 88 cases. Overall, although tetracycline-containing regimens showed encouraging results, more data from larger comparative trials are required to establish a role for these antibiotics in the treatment of MDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Doxycycline; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Minocycline; Respiratory Tract Infections; Survival Analysis; Treatment Outcome

Carbapenem-resistant Acinetobacter baumannii (CRAB) constitutes an increasing problem worldwide. CRAB bacteremia is associated with a high fatality rate and its optimal treatment has not been established. Early institution of appropriate therapy is shown to improve survival of patients with CRAB bloodstream infection. Regrettably, treatment options are limited. Little information exists about the efficacy of sulbactam for the treatment of CRAB bacteremia. Colistin and tigecycline possess good in vitro activity and represent in many cases the only therapeutic options although clinical data are scarce. The need for a loading dose of colistin has been recently demonstrated to rapidly achieve therapeutic levels. The use of combination therapy is also a matter of debate but current evidence do not support its routine use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulbactam; 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

In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was higher in the tigecycline group versus the comparator group. Study-level mortality risk differences were pooled using a random-effects meta-analysis. Statistical models evaluated the association between patient-level all-cause mortality and baseline factors using logistic regression, recursive partitioning [classification and regression tree (CART) analysis] and survival techniques. The estimated risk difference (tigecycline minus comparator) in all-cause mortality from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical modelling identified baseline bacteraemia associated with mortality only in the tigecycline group. In patients with ventilator-associated pneumonia (VAP) and baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7% (1/13) for the comparator group. Study-level and patient-level analyses have identified that patients in the hospital-acquired pneumonia trial, particularly those with VAP with baseline bacteraemia, were at a higher risk of clinical failure and mortality.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Survival Analysis; Tigecycline; Treatment Outcome

Klebsiella pneumoniae carbapenemases (KPCs) were originally identified in the USA in 1996. Since then, these versatile β-lactamases have spread internationally among Gram-negative bacteria, especially K pneumoniae, although their precise epidemiology is diverse across countries and regions. The mortality described among patients infected with organisms positive for KPC is high, perhaps as a result of the limited antibiotic options remaining (often colistin, tigecycline, or aminoglycosides). Triple drug combinations using colistin, tigecycline, and imipenem have recently been associated with improved survival among patients with bacteraemia. In this Review, we summarise the epidemiology of KPCs across continents, and discuss issues around detection, present antibiotic options and those in development, treatment outcome and mortality, and infection control. In view of the limitations of present treatments and the paucity of new drugs in the pipeline, infection control must be our primary defence for now.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Communicable Disease Control; Geography; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Tigecycline; Treatment Outcome

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p= 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p= 0.02); similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p= 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical trials.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Drug Combinations; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Polymyxins; Tigecycline; Treatment Outcome

Severe (life-threatening) meticillin-resistant Staphylococcus aureus (MRSA) infection continues to be treated with vancomycin despite accumulating evidence of poor outcome, increasing resistance and unachievable pharmacokinetic/pharmacodynamic (PK/PD) targets. The minimum inhibitory concentration (MIC) susceptibility breakpoint for vancomycin was recently reduced to 2 mg/L. Whilst the great majority of clinical isolates are thus still classified as susceptible, the available clinical evidence argues for a method-dependent breakpoint of 0.5 mg/L (broth dilution) or 1.0 mg/L (Etest), which would classify many strains as resistant, or at best intermediate. However, automated susceptibility testing systems are not currently capable of performing accurately at this low level, and such low breakpoints are unsatisfactory because the poor reproducibility of tests (plus or minus one doubling dilution) results in a critical non-reproducibility around the modal MIC of 1 mg/L described in most published data. Therefore, vancomycin should be used with caution in severe (life-threatening) staphylococcal disease and the MIC should always be reported by method. Daptomycin is generally preferred for bacteraemia/endocarditis and linezolid for pneumonia. Better outcome data for vancomycin, based on achievable PK/PD targets and using robust MIC tests, are urgently required.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Endocarditis, Bacterial; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Pneumonia, Bacterial; Staphylococcal Infections; Teicoplanin; Tigecycline; Treatment Outcome; Vancomycin

A 73-year-old man on hemodialysis with a tunneled central venous catheter presented to the emergency room with a fever and severe back pain.. Physical examination, laboratory investigations, chest radiography, lumbar spine radiography, renal ultrasound, lumbosacral spine MRI and transthoracic echocardiography.. Spondylodiscitis as a result of methicillin-sensitive Staphylococcus aureus bacteremia.. Antibiotic therapy with intravenous cefazolin for 6 weeks and oral minocycline for 2 weeks.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cefazolin; Discitis; Humans; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Minocycline; Staphylococcal Infections

High-dose interleukin-2 (HDIL-2) has proven to be an effective treatment for metastatic renal cell carcinoma and melanoma. Previous studies have shown an increase in catheter-related bacteremia (CRB) in patients on HDIL-2. The primary objective of this study was to evaluate the effectiveness of minocycline and rifampin-coated catheters (M/R-C) in reducing CRB in cancer patients on HDIL-2. This was a retrospective study where non-coated catheters (NC-C) and M/R-C were used for the administration of HDIL-2 before and after December 2004, respectively. Data collected included demographics, cancer type, catheter type, antibiotic prophylaxis, and infection rates. A total of 107 episodes of catheter use for HDIL-2 were evaluated in 78 patients (30 episodes in patients with M/R-C vs. 77 with NC-C). A total of nine episodes of CRB were identified, all in patients with NC-C (M/R-C 0% vs. NC-C 12%; p=0.06). The median time to bacteremia was 11 days (range 1-315 days). A log-rank test showed a trend that the M/R-C group had lower probability of getting CRB than the NC-C group (p=0.06). The use of M/R-C in patients on HDIL-2 therapy for advanced melanoma and renal cell carcinoma may have reduced the risk of CRB to nil. CRB still occurred despite antibiotic prophylaxis in patients with NC-C.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Female; Humans; Interleukin-2; Male; Middle Aged; Minocycline; Neoplasms; Rifampin; Treatment Outcome

Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens in the nosocomial and community setting. Hospitalization costs associated with MRSA infections are substantially greater than those associated with methicillin-sensitive S. aureus (MSSA) infections, and MRSA has wider economic effects that involve indirect costs to the patient and to society. In addition, there is some evidence suggesting that MRSA infections increase morbidity and the risk of mortality. Glycopeptides are the backbone antibiotics for the treatment of MRSA infections. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Several new antimicrobials demonstrate in vitro activity against MRSA and other Gram-positive bacteria. Data from large surveys indicate that linezolid, daptomycin, and tigecycline are almost universally active against MRSA. This review will briefly discuss the epidemiology, costs, outcome, and therapeutic options for the management of MRSA infections.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Cross Infection; Daptomycin; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Staphylococcal Infections; Tigecycline; Treatment Outcome

The use of antimicrobial-impregnated central venous catheters (CVCs) for the prevention of CVC microbial colonization and catheter-related bloodstream infection (CRBSI) remains controversial.. We performed a meta-analysis of randomized controlled trials (RCTs) evaluating CRBSI and colonization of CVCs impregnated with rifampicin-based antimicrobial combinations. Our main analysis compared the occurrence of CRBSI with rifampicin/minocycline-impregnated CVCs with that of non-rifampicin-impregnated CVCs. The PubMed and Cochrane Central Register of Controlled Trials databases were searched (until October 2006).. Eight RCTs were included in the analysis. The main analysis (seven RCTs) demonstrated that rifampicin/minocycline-impregnated CVCs were associated with fewer CRBSIs compared with catheters not impregnated with rifampicin/minocycline (OR 0.23, 95% CI 0.14-0.40). The same was true regarding colonization (OR 0.46, 95% CI 0.31-0.69). Further analysis, comparing rifampicin-based CVCs with non-rifampicin-impregnated CVCs, demonstrated superiority of rifampicin-based CVCs in reducing colonization (OR 0.38, 95% CI 0.24-0.62) and CRBSI (OR 0.24, 95% CI 0.14-0.40). Similar results, suggesting superiority of rifampicin/minocycline-impregnated CVCs, were noted in a subgroup analysis of colonization and CRBSIs in which rifampicin/minocycline-impregnated CVCs were compared with simple, non-tunnelled, non-antimicrobially impregnated CVCs, a subgroup analysis that was performed by excluding low quality RCTs, and a subgroup analysis for colonization comprising studies in which the sonication technique was used. No serious adverse events and no difference in mortality between the two treatment groups were reported. No clear conclusions can be made regarding the impact of the use of rifampicin/minocycline-impregnated CVCs on the development of antimicrobial resistance based on the available data.. The available evidence suggests that rifampicin/minocycline-impregnated CVCs are safe and effective in reducing the rate of catheter colonization and CRBSI. Further research should focus on the possible development of resistance and on pharmacoeconomic issues related to the use of rifampicin/minocycline-impregnated CVCs.

Topics: Bacteremia; Catheterization, Central Venous; Chlorhexidine; Humans; Minocycline; Randomized Controlled Trials as Topic; Rifampin; Silver Sulfadiazine

A 50-year-old woman was admitted to our hospital because of MRSA septicemia caused by a contaminated permanent pacemaker lead. A pacemaker system was successfully removed under cardiopulmonary bypass support. Postoperative antibiotics was administered for 7 weeks. Total removal of a pacemaker system under cardiopulmonary bypass support is the treatment of choice in a case with pacemaker infection associated with MRSA septicemia.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cardiopulmonary Bypass; Dibekacin; Drug Therapy, Combination; Female; Humans; Methicillin Resistance; Middle Aged; Minocycline; Pacemaker, Artificial; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Vascular catheters impregnated with antimicrobial agents have been shown to decrease the risk of catheter-related colonization and bloodstream infections. Various antimicrobials and antiseptics have been used. In a recent meta-analysis of 12 studies, catheters coated with chlorhexidine and silver sulfadiazine (CH/SS) were shown to be significantly less likely to be associated with catheter-related bloodstream infections than uncoated catheters. However, these catheters were coated only on the external surface and they are associated with short antimicrobial durability (3-7 days). In addition, anaphylactic reactions to them were reported in Japan. Vascular catheters impregnated with minocycline and rifampin (M/R) were found to be highly efficacious in preventing catheter-related infections. In a recent prospective, randomized trial, the likelihood of catheter-related bloodstream infections associated with the use of M/R catheters was one-twelfth of that observed with catheters coated with CH/SS. The M/R catheters are coated on the external and internal surfaces and have an antimicrobial durability of 4 weeks. Although no resistance to either minocycline or rifampin has been seen in two trials, further studies are required to determine whether the risk of resistance outweighs the benefits derived from their use. In conclusion, antimicrobial catheters have been shown to be highly cost effective in decreasing the risk of catheter-related bloodstream infection.

Topics: Anaphylaxis; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Infective Agents, Local; Bacteremia; Bacterial Infections; Catheters, Indwelling; Chlorhexidine; Coated Materials, Biocompatible; Enzyme Inhibitors; Humans; Minocycline; Rifampin; Risk Assessment; Risk Factors; Silver Sulfadiazine

The use of long-term central venous catheters (CVCs) could lead to serious bloodstream infections. Removal of the infected CVC and reinsertion of a new CVC are not always feasible and alternative lock therapy may be considered. We conducted a multicenter trial to assess the efficacy and safety of the lock therapy.. Between October 2013 and August 2014, we prospectively enrolled 20 patients with catheter-related bloodstream infections (CRBSIs) or central line-associated bloodstream infections (CLABSIs) in our sister institutions in three countries including Brazil, Lebanon, and Japan. The 20 patients who received M-EDTA-EtOH lock therapy were compared to 24 control patients who had their CVCs removed and a new CVC inserted.. Both groups had comparable clinical characteristics. In the lock therapy group, 95% of the patients had microbiological eradication within 96 h after starting lock therapy versus 83% of the patients in the control group (p = .36). In the lock group, the CVC was salvaged and retained for a median of 21 days (range 7-51) from the onset of bacteremia.. Our study suggests that M-EDTA-EtOH lock therapy may be an effective intervention to salvage long-term CVCs in the setting of CLABSI/CRBSI and hemodialysis cancer patients with limited vascular access.

Topics: Bacteremia; Edetic Acid; Ethanol; Female; Humans; Male; Middle Aged; Minocycline; Salvage Therapy

Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care.. We did a randomised controlled trial of children admitted to 14 English paediatric intensive care units. Children younger than 16 years were eligible if they were admitted or being prepared for admission to a participating paediatric intensive care unit and were expected to need a central venous catheter for 3 or more days. Children were randomly assigned (1:1:1) to receive a central venous catheter impregnated with antibiotics, a central venous catheter impregnated with heparin, or a standard central venous catheter with computer generated randomisation in blocks of three and six, stratified by method of consent, site, and envelope storage location within the site. The clinician responsible for inserting the central venous catheter was not masked to allocation, but allocation was concealed from patients, their parents, and the paediatric intensive care unit personnel responsible for their care. The primary outcome was time to first bloodstream infection between 48 h after randomisation and 48 h after central venous catheter removal with impregnated (antibiotic or heparin) versus standard central venous catheters, assessed in the intention-to-treat population. Safety analyses compared central venous catheter-related adverse events in the subset of children for whom central venous catheter insertion was attempted (per-protocol population). This trial is registered with ISRCTN number, ISRCTN34884569.. Between Nov 25, 2010, and Nov 30, 2012, 1485 children were recruited to this study. We randomly assigned 502 children to receive standard central venous catheters, 486 to receive antibiotic-impregnated catheters, and 497 to receive heparin-impregnated catheters. Bloodstream infection occurred in 18 (4%) of those in the standard catheters group, 7 (1%) in the antibiotic-impregnated group, and 17 (3%) assigned to heparin-impregnated catheters. Primary analyses showed no effect of impregnated (antibiotic or heparin) catheters compared with standard central venous catheters (hazard ratio [HR] for time to first bloodstream infection 0.71, 95% CI 0.37-1.34). Secondary analyses showed that antibiotic central venous catheters were better than standard central venous catheters (HR 0.43, 0.20-0.96) and heparin central venous catheters (HR 0.42, 0.19-0.93), but heparin did not differ from standard central venous catheters (HR 1.04, 0.53-2.03). Clinically important and statistically significant absolute risk differences were identified only for antibiotic-impregnated catheters versus standard catheters (-2.15%, 95% CI -4.09 to -0.20; number needed to treat [NNT] 47, 95% CI 25-500) and antibiotic-impregnated catheters versus heparin-impregnated catheters (-1.98%, -3.90 to -0.06, NNT 51, 26-1667). Nine children (2%) in the standard central venous catheter group, 14 (3%) in the antibiotic-impregnated group, and 8 (2%) in the heparin-impregnated group had catheter-related adverse events. 45 (8%) in the standard group, 35 (8%) antibiotic-impregnated group, and 29 (6%) in the heparin-impregnated group died during the study.. Antibiotic-impregnated central venous catheters significantly reduced the risk of bloodstream infections compared with standard and heparin central venous catheters. Widespread use of antibiotic-impregnated central venous catheters could help prevent bloodstream infections in paediatric intensive care units.. National Institute for Health Research, UK.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Candidemia; Catheter-Related Infections; Catheterization, Central Venous; Central Venous Catheters; Child; Child, Preschool; Female; Fibrinolytic Agents; Heparin; Humans; Infant; Male; Minocycline; Rifampin

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.).

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Biofilms; Catheter-Related Infections; Catheterization, Central Venous; Central Venous Catheters; Edetic Acid; Ethanol; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Pilot Projects; Prospective Studies; Treatment Outcome; Young Adult

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiratory Tract Infections; Treatment Outcome

Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria.. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment.. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups.. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Chemotherapy-Induced Febrile Neutropenia; Drug Combinations; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Tigecycline; Young Adult

In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was higher in the tigecycline group versus the comparator group. Study-level mortality risk differences were pooled using a random-effects meta-analysis. Statistical models evaluated the association between patient-level all-cause mortality and baseline factors using logistic regression, recursive partitioning [classification and regression tree (CART) analysis] and survival techniques. The estimated risk difference (tigecycline minus comparator) in all-cause mortality from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical modelling identified baseline bacteraemia associated with mortality only in the tigecycline group. In patients with ventilator-associated pneumonia (VAP) and baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7% (1/13) for the comparator group. Study-level and patient-level analyses have identified that patients in the hospital-acquired pneumonia trial, particularly those with VAP with baseline bacteraemia, were at a higher risk of clinical failure and mortality.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Survival Analysis; Tigecycline; Treatment Outcome

There is growing concern about the development of antibacterial resistance with the use of antibiotics in catheter lock solutions. The use of an antibiotic that is not usually used to treat other serious infections may be an alternative that may reduce the clinical impact should resistance develop. We conducted a randomized controlled trial to compare a solution of minocycline and EDTA with the conventional unfractionated heparin for the prevention of catheter-related bacteremia in hemodialysis patients during a period of 90 d. The study included 204 incident catheters (27.8% tunneled); 14 catheters were excluded because of early dysfunction and 3 because of protocol violations. We observed catheter-related bacteremia in 19 patients in the heparin group (4.3 per 1000 catheter-days) and in 5 patients in the minocycline-EDTA group (1.1 per 1000 catheter-days; P = 0.005). We did not detect a significant difference in the rate of catheter removal for dysfunction. Catheter-related bacteremia-free survival was significantly higher in the minocycline-EDTA group than in the heparin group (P = 0.005). In conclusion, a minocycline-EDTA catheter lock solution is effective in the prevention of catheter-related bacteremia in hemodialysis patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Anticoagulants; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Edetic Acid; Female; Heparin; Humans; Male; Middle Aged; Minocycline; Renal Dialysis; Survival Analysis

Tigecycline is effective in the treatment of complicated skin/skin-structure infection (cSSSI), complicated intraabdominal infection (cIAI), and community-acquired bacterial pneumonia (CAP), but its efficacy in subjects with secondary bacteremia is unknown.. Pooled data from subjects enrolled for treatment of cSSSI, cIAI, or CAP presenting with bacteremia from 7 double-blind and 1 open-label trial of tigecycline compared with vancomycin-aztreonam, imipenem-cilastatin, levofloxacin, vancomycin, or linezolid were analyzed. The primary efficacy end point was the clinical cure rate at the test-of-cure assessment.. A total of 170 subjects were identified (91 tigecycline recipients and 79 recipients of the comparator agent). Clinical cure rates were 81.3% and 78.5% for tigecycline and the comparator, respectively (P = .702). Analysis by sex, age, creatinine clearance, infection site, Acute Physiology and Chronic Health Evaluation score, and Fine score demonstrated no significant between-group differences. Clinical cure rates for the most commonly represented pathogens (Staphylococcus aureus, Streptococcus pneumoniae, and gram-negative species) were also not significantly different between treatment groups. No decrease in the rate of cure was found in organisms with increasing tigecycline minimum inhibitory concentrations. Nine subjects treated with tigecycline and 1 subject treated with comparator were found to have persistent bacteremia. No clinically significant differences in safety parameters were identified.. Tigecycline was generally safe and well tolerated in the treatment of secondary bacteremia associated with cSSSI, cIAI, and CAP; cure rates were similar to comparative standard therapies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Middle Aged; Minocycline; Prospective Studies; Tigecycline; Young Adult

The Tigecycline Evaluation and Surveillance Trial is a global surveillance study established in 2004 to monitor the activity of tigecycline, a new glycylcycline, and several comparators against an array of important Gram-positive and Gram-negative pathogens. In this study, we examined 1591 isolates of Acinetobacter from blood samples collected from 352 centers globally between 2004 and 2008. Tigecycline showed an MIC(90) (1 microg/mL) globally, with a maximum regional value of 4 microg/mL (Middle East) reported. Antimicrobial susceptibility was notably higher among nonintensive care unit (non-ICU) isolates than isolates collected from ICUs. Carbapenem-resistant Acinetobacter were more prevalent in the Middle East, Latin America, and Asia/Pacific rim than in Europe or North America. Tigecycline creep was noted between 2004 and 2007, corresponding closely to changes in MIC(90).

Topics: Acinetobacter; Anti-Bacterial Agents; Asia; Bacteremia; Blood; Culture Media; Drug Resistance, Bacterial; Europe; Humans; Intensive Care Units; Latin America; Microbial Sensitivity Tests; Minocycline; North America; Population Surveillance; Tigecycline

We evaluated a catheter-lock solution consisting of N-acetylcysteine, tigecycline, and heparin for catheter salvage in patients with hemodialysis catheter-associated bacteremia. Eighteen case patients received the catheter-lock solution for 14 days plus systemic antibiotic therapy. Treatment was successful for 15 (83%) of the 18 case patients within 90 days of follow-up, with a median catheter retention interval of 64.5 days.

Topics: Acetylcysteine; Anti-Bacterial Agents; Bacteremia; Catheterization; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Pilot Projects; Prospective Studies; Renal Dialysis; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Drug Administration Schedule; Drug Resistance, Multiple; Gram-Negative Bacterial Infections; Humans; Minocycline; Tigecycline

Central venous catheters are the predominant cause of nosocomial bacteremia; however, the effectiveness of different antimicrobial central venous catheters remains uncertain. We compared the infection rate of silver-platinum-carbon (SPC)-impregnated catheters with rifampicin-minocycline (RM)-coated catheters.. A large, single-center, prospective randomized study.. Twenty-two-bed adult general intensive care unit in a large tertiary metropolitan hospital in Brisbane, Australia (2000-2001).. Consecutive series of all central venous catheterizations in intensive care unit patients.. Randomization, concealment, and blinding were carefully performed. Catheter insertion and care were performed according to published guidelines. Blood cultures were taken at central venous catheter removal, and catheter-tip cultures were performed by both roll-plate and sonication techniques. Pulsed field gel electrophoresis was used to establish shared clonal origin for matched isolates.. Central venous catheter colonization and catheter-related bloodstream infection were determined with a blinded technique using the evaluation of the extensive microbiological and clinical data collected and a rigorous classification system. Six hundred forty-six central venous catheters (RM 319, SPC 327) were inserted, and 574 (89%) were microbiologically evaluable. Colonization rates were lower for the RM catheters than SPC catheters (25 of 280, 8.9%; 43 of 294, 14.6%; p=.039). A Kaplan-Meier analysis that included catheter time in situ did not quite achieve statistical significance (p=.055). Catheter-related bloodstream infection was infrequent for both catheter-types (RM 4, 1.4%; SPC 5, 1.7%).. The SPC catheter is a clinically effective antimicrobial catheter; however, the RM catheter had a lower colonization rate. Both catheter types had low rates of catheter-related bloodstream infection. These results indicate that future studies will require similar rigorous methodology and thousands of central venous catheters to demonstrate differences in catheter-related bloodstream infection rates.

Topics: Anti-Infective Agents, Local; Bacteremia; Carbon; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Equipment Contamination; Female; Humans; Logistic Models; Male; Middle Aged; Minocycline; Platinum; Prospective Studies; Queensland; Rifampin; Silver

Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia (CRB), but insufficient data are available about the ideal agent and dose. We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past.. In this prospective, open-labeled, randomized, clinical trial of patients on long-term hemodialysis therapy, patients were randomly assigned to administration of an antibiotic lock solution of gentamicin/citrate (4 mg/mL), minocycline/EDTA, or the control solution of heparin. Patients were followed up until the study end point of CRB was reached or a censoring event occurred. Interim data analysis was performed after 6 months to assess data safety; efficacy was noted and the study was terminated early.. Sixty-two patients were enrolled into the study, evenly distributed in 3 arms, with data from 1 patient excluded from analysis. Seven of 20 patients in the heparin group (4.0 events/1,000 catheter days), 1 of 21 patients in the minocycline group (0.4 events/1,000 catheter days), and none of 20 patients in the gentamicin group developed bacteremia. Results were statistically significant by using 2-tailed Fisher exact test; heparin versus gentamicin, P = 0.008, and heparin versus minocycline, P = 0.020.. Antibiotic lock solutions are superior to the standard heparin lock alone in the prevention of CRBs, and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization; Dose-Response Relationship, Drug; Female; Gentamicins; Humans; Infection Control; Male; Middle Aged; Minocycline; Prospective Studies; Renal Dialysis; Staphylococcus aureus

To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections.. This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy.. Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (+/- standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 +/- 30.88 v 63.01 +/- 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters.. Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Double-Blind Method; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Prospective Studies; Rifampin; Silicones

To determine the cost-effectiveness of the newer antiseptic and antibiotic-impregnated central venous catheters (CVCs) relative to uncoated CVCs and to each other.. Decision model analysis of the cost and efficacy of CVCs coated with either chlorhexidine silver sulfadiazine (CSS) or rifampin-minocycline (RM) at preventing catheter-related bloodstream infections (CRBSIs). The primary outcome is the incremental cost (or savings) to prevent one additional CRBSI. Model estimates are derived from prospective trials of the CSS and RM CVCs and from other studies describing the costs of CRBSIs.. Hypothetical cohort of 1,000 patients requiring placement of a CVC.. In the model, patients were managed with either an uncoated CVC, CSS CVC, or RM CVC.. The incremental cost-effectiveness of the treated CVCs was calculated as the savings resulting from CRBSIs averted less the additional costs of the newer devices. Sensitivity analysis of the effect of the major clinical inputs was performed. For the base case analysis, we assumed the incidence of CRBSIs was 3.3% with traditional catheters and that the CSS and RM CVC conferred a relative risk reduction for the development of CRBSIs of 60% and 85%, respectively. Despite their significantly higher cost than older catheters, both novel CVCs yield significant savings. Employing either of the treated CVCs saves approximately $10,000 per CRBSI prevented (relative to standard catheters). Comparing the RM CVC to the CSS CVC revealed the RM product to be economically superior, saving nearly $9,600 per CRBSI averted and $81 per patient in the cohort. For sensitivity analysis, we adjusted all model variables by 50% individually and then simultaneously. This demonstrated the model to be most sensitive to the cost of a CRBSI; however, with all inputs skewed by 50% against both the CSS CVC and the RM CVC, these devices remained economically attractive. Under this scenario, use of either treated device was less costly.. Utilization of antiseptic and antibiotic-impregnated CVCs represent an attractive alternative for the prevention of CRBSIs and may lead to significant savings. Of the two newer, coated devices, the RM CVC performs better financially. These observations hold over a range of estimates for our model inputs.

Topics: Bacteremia; Catheterization, Central Venous; Chlorhexidine; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Support Techniques; Humans; Minocycline; Rifampin; Sensitivity and Specificity; Silver Sulfadiazine

The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters.. We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated.. Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002).. The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

Topics: Analysis of Variance; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteremia; Bacteria; Catheterization, Central Venous; Chlorhexidine; DNA Fingerprinting; Equipment Contamination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Prospective Studies; Rifampin; Risk Factors; Silver Sulfadiazine

Elizabethkingia meningoseptica is a non-fermentative Gram-negative bacillus that has emerged as an important pathogen in nosocomial infections and is usually associated with high mortality. E. meningoseptica is inherently resistant to many broad-spectrum antibiotics, and appropriate antibiotic selection is crucial for survival. Data about the therapeutic efficacy of fluoroquinolone in E. meningoseptica bacteraemia are limited. We retrospectively enrolled patients with E. meningoseptica bacteraemia who were treated with a single antimicrobial agent with in vitro activity against E. meningoseptica for at least 48 hours in a Taiwanese medical centre between January 2011 and June 2016. We compared the therapeutic efficacy of fluoroquinolone and non-fluoroquinolone treatment. A logistic regression and a propensity score-adjusted model were used to evaluate the risk factors for 14-day mortality. A total of 66 patients were identified, 24 who received fluoroquinolone treatment (ciprofloxacin, n = 9; levofloxacin, n = 15) and 42 who received non-fluoroquinolone treatment (piperacillin/tazobactam, n = 26; trimethoprim/sulfamethoxazole, n = 15; minocycline, n = 1). The fluoroquinolone group had significantly lower 14-day mortality than the non-fluoroquinolone group (8.3% vs. 33.3%, P = 0.023). The APACHE II score was significantly higher in the non-fluoroquinolone group than in the fluoroquinolone group. In a propensity-adjusted analysis, fluoroquinolone use was an independent factor associated with 14-day survival. After stratification using the APACHE II score, treatment with fluoroquinolone was associated with 14-day survival, but did not reach statistical significance in both groups with greater and lesser severity. Therefore, fluoroquinolone is a suitable antimicrobial agent for treating E. meningoseptica bacteraemia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Cross Infection; Female; Flavobacteriaceae Infections; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

Acinetobacter baumannii infections in neonates are not uncommon but rarely studied.. Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed.. Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-bla. To reduce mortality of IRAB infection, it is crucial to consider giving effective agents, such as colistin, in 2 days for high risk neonates who has been given imipenem or used HFOV.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Multilocus Sequence Typing; Polymerase Chain Reaction; Risk Factors; Taiwan; Tigecycline

To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).. Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.. 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20-1.43, P <0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19-4.50, P <0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02-2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25-0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47-1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43-0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L.. In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.

Topics: Aged; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Propensity Score; Tertiary Care Centers; Tigecycline; Treatment Outcome

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

Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus.. We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used.. Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p < 0.05) in SICU patients.. Routine use of rifampin-minocycline-impregnated CVCs in the SICU was not associated with increased resistance of S. aureus isolates to rifampin or tetracyclines.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Drug Resistance, Bacterial; Hospitals, Teaching; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Urban Population

The higher 14-day mortality rate for patients with Acinetobacter bacteremia receiving tigecycline appropriately compared to other appropriate antibiotics (36.4% versus 14.2%, P = 0.028) was due to the poor effect of tigecycline for isolates with a minimum inhibitory concentration of 2 μg/mL (63.6% of 11 versus 14.2% of 127, P = 0.001).

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mortality; Prospective Studies; Retrospective Studies; Taiwan; Tigecycline; Treatment Outcome

Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) has become increasingly frequent threat recently, especially in the intensive care unit (ICU). High-dose tigecycline (TGC) regimen is proposed due to the limitation of treatment options. We investigated the efficacy and safety of high-dose TGC combination regimens for treating CRKP BSI. Furthermore, the risk factors for mortality were also determined.This was a single center retrospective cohort study conducted from 2014 to 2016. A total of 40 patients with nosocomial CRKP BSI admitted to the ICU were included; they were classified into two groups according to the treatment regimens with high-dose TGC (HD group) or not (non-HD group). In-hospital mortality rates and microbiologic responses from both groups were reviewed and compared. Besides, the survival and non-survival groups were compared to identify the risk factors of mortality.Twenty-three patients constituted the HD group (high-dosage TGC regimen was administered as 200 mg loading dose followed by 100 mg every 12 h) and 17 patients constituted the non-HD group (standard dose TGC therapy as 100 mg loading dose followed by 50 mg every 12 h and other antibiotics). The in-hospital mortality was 52.2% in the HD group and 76.5% in the non-HD group (P = .117). The Kaplan-Meier test showed significantly longer survival times in the HD group (mean: 83 days vs 28 days; P = .027). Microbiological eradication was observed in 13 patients (56.5%) in the HD group and 6 patients (36.3%) in the non-HD group (P = .184). A smaller fraction of patients in the HD group were subjected to vasoactive therapy (52.2% vs 88.2%; P = .016) compared to the non-HD group. There was no significant difference in the manifestation of adverse effects between the two groups. In the multivariate analysis, multiple organ dysfunction syndrome (MODS), vasoactive therapy, and exposure to carbapenems were regarded as the independent predictors of mortality.A therapeutic regimen consisting of a high dose of TGC was associated with significantly longer survival time and numerically lower mortality in CRKP BSI. Adverse events were not increased with the double dose therapy.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Colistin; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Bacterial; Female; Hospitalization; Humans; Infant; Infant, Newborn; Intensive Care Units; Lebanon; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mortality; Prevalence; Respiration, Artificial; Retrospective Studies; Risk Factors; Shock, Septic; Steroids; Tigecycline; Treatment Outcome; Young Adult

A 63-year-old man with follicular lymphoma was administered standard R-CHOP chemotherapy. Six days after the second course of chemotherapy, the patient developed fever and chills. Blood cultures yielded rod-shaped gram-negative bacteria, but no further identification was obtained. High fever and chills returned on the fifth and sixth days after the third and fourth courses of R-CHOP, respectively. These blood cultures were also positive. Since we detected spiral-shaped gram-negative rods, we performed a prolonged culture during the febrile period after the fourth course of R-CHOP. This revealed the formation of characteristic film-like colonies, and Helicobacter cinaedi(H. cinaedi)bacteria was identified. After final identification, the patient was administered prophylactic minocycline treatment. Subsequent blood cultures were negative, fever did not recur, and we were able to complete 6 courses of R-CHOP. Although H. cinaedi has been reported to be a cause of sepsis in immunocompromised patients, standard correlation has not been established. Our case suggests that H. cinaedi should be considered when recurrent fever is observed after chemotherapy. Prophylactic antibiotic treatment with minocycline may prevent sepsis, as observed in our case.

Topics: Anti-Bacterial Agents; Bacteremia; Helicobacter Infections; Humans; Lymphoma, Follicular; Male; Middle Aged; Minocycline; Recurrence; Sepsis

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.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Humans; Infant; Liver Transplantation; Male; Minocycline; Tigecycline

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.. 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 ≥4μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia.. 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 20mg 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).. 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.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Disease Susceptibility; Drug Resistance, Bacterial; Female; Humans; Immunocompromised Host; Male; Middle Aged; Minocycline; Risk Factors; Tigecycline

European centers (n = 226) involved in the Tigecycline Evaluation and Surveillance Trial (TEST, 2004-2014) submitted data and bacterial isolates.. Minimal inhibitory concentrations and susceptibility were determined using Clinical and Laboratory Standards Institute methods and European Committee on Antimicrobial Susceptibility Testing breakpoints.. The rates of the following resistant pathogens increased from 2004 to 2014: extended-spectrum β-lactamase (ESBL)-positive Escherichia coli (from 8.9 to 16.9%), multidrug-resistant Acinetobacter baumannii complex (from 15.4 to 48.5%), and ESBL-positive Klebsiella pneumoniae (from 17.2 to 23.7%). The rate of methicillin-resistant Staphylococcus aureus was 27.5% in 2004 and 28.9% in 2014. Resistance to the carbapenems (imipenem and meropenem) was 37.4 and 14.5% for A. baumannii complex and Pseudomonas aeruginosa, respectively. Carbapenem resistance was ≤4.3% among the Enterobacteriaceae and 0.2% against Streptococcus pneumoniae. The resistance to tigecycline ranged between 7.4% against ESBL-producing K. pneumoniae and 0.0% against S. aureus.. The carbapenems and tigecycline were active against Enterobacteriaceae. Agents with activity against A. baumannii complex and P. aeruginosa are limited. The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Thienamycins; Tigecycline

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

The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia.. In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed.. SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy.. The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Clavulanic Acids; Drug Therapy, Combination; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Middle Aged; Minocycline; Neoplasms; Stenotrophomonas maltophilia; Ticarcillin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Identification of risks of mortality for carbapenem-resistant Acinetobacter baumannii (CRAB), with early implementation of an appropriate therapy, is crucial for the patients' outcome. The aim of this study was to survey mortality risk factors in 182 patients with CRAB bacteremia in a medical center in Taiwan.. A total of 182 isolates of CRAB bacteremia were collected from 2009 to 2012 in Mackay Memorial Hospital, Taipei, Taiwan These isolates were identified by using the genotypic method. Risk of attributable mortality analysis was carried out with a Cox proportional hazards model.. The 182 CRAB isolates belonged to 38 different pulsotypes. The attributable mortality rate of the 182 patients was 58.24%. The risk factors for attributable mortality included intensive care unit stay [hazard ratio (HR): 2.27; p = 0.011], an Acute Physiology and Chronic Health Evaluation II score of >20 (HR: 2.19; p < 0.001), respiratory tract as the origin of bacteremia (HR: 3.40; p < 0.001), and previous use of ceftriaxone (HR: 2.51; p = 0.011). The appropriateness of antimicrobial therapy was 18.87% (20/106) in the mortality group versus 88.16% (67/76) in the survivor group (p < 0.001). The sensitivity of CRAB to colistin was 100% and to tigecycline was 40.11%.. The risk factors for mortality for CRAB included intensive care unit stay, a high Acute Physiology and Chronic Health Evaluation II score, respiratory tract as the origin of bacteremia, and previous use of ceftriaxone. Early implementation of an antimicrobial agent that had the highest in vitro activity against CRAB in patients at risk of CRAB bacteremia and high mortality may improve their outcome.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; APACHE; Bacteremia; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Tigecycline

To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy.. The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients.. We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality.. Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Salvage Therapy; Sulbactam; Taiwan; Tigecycline; Treatment Outcome

Serious infections in intensive care unit patients caused by multidrug-resistant (MDR) Klebsiella pneumoniae represent a major threat worldwide owing to increased mortality and limited treatment options. With the application of tigecycline for MDR pathogens, tigecycline-non-susceptible K. pneumoniae isolates have recently emerged in China. To identify the susceptibility profile of MDR K. pneumoniae to tigecycline and evaluate the molecular characterization of tigecycline resistance, 214 MDR K. pneumoniae isolates were collected from blood samples of patients in intensive care units. MICs and clonal relatedness were determined by standard broth microdilution and multilocus sequence typing, respectively. Expression levels of efflux pumps and their global regulators were examined using real-time PCR. Mutations of local repressor were identified by PCR and sequencing. Our results show that the tigecycline resistance rate of 214 MDR K. pneumoniae isolates was 6.07 %. ST11 was the predominant clone type of tigecycline-non-susceptible K. pneumoniae isolates. Expression of efflux pump AcrB and global regulator RamA correlated with tigecycline MICs (AcrB: x2=8.91, P=0.03; RamA: x2=13.91, P<0.01), and mean expression levels of AcrB for the MICs ≥4 mg l-1 were significantly higher than MICs ≤2 mg l-1 (t=2.48, P=0.029). In addition, one tigecycline-resistant isolate harboured a deletion mutation in the ramR gene. These data indicated a linear correlative trend for overexpression of the AcrB and the tigecycline MICs resulting from the upregulation of RamA. The emergence of molecular type ST11 of MDR K. pneumoniae isolates should be monitored to identify factors that contribute to tigecycline resistance in intensive care units.

Topics: Anti-Bacterial Agents; Bacteremia; China; DNA Mutational Analysis; Drug Resistance, Multiple, Bacterial; Gene Expression Profiling; Genes, Regulator; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Multidrug Resistance-Associated Proteins; Multilocus Sequence Typing; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA; Tigecycline

A rise in tigecycline resistance in Klebsiella pneumoniae has been reported recently worldwide. We sought to identify risk factors, outcomes, and mechanisms for adult patients with tigecycline-nonsusceptible K. pneumoniae bacteremia in Taiwan. We conducted a matched case-control study (ratio of 1:1) in a medical center in Taiwan from January 2011 through June 2015. The cases were patients with tigecycline-nonsusceptible K. pneumoniae bacteremia, and the controls were patients with tigecycline-susceptible K. pneumoniae bacteremia. Logistic regression was performed to evaluate the potential risk factors for tigecycline-nonsusceptible K. pneumoniae bacteremia. Quantitative reverse transcription-PCR was performed to analyze acrA, oqxA, ramA, rarA, and kpgA expression among these isolates. A total of 43 cases were matched with 43 controls. The 14-day mortality of patients with tigecycline-nonsusceptible K. pneumoniae bacteremia was 30.2%, and the 28-day mortality was 41.9%. The attributable mortalities of tigecycline-nonsusceptible K. pneumoniae at 14 and 28 days were 9.3 and 18.6%, respectively. Fluoroquinolone use within 30 days prior to bacteremia was the only independent risk factor for tigecycline-nonsusceptible K. pneumoniae bacteremia. The tigecycline-nonsusceptible K. pneumoniae bacteremia was mostly caused by overexpression of AcrAB and/or OqxAB efflux pumps, together with the upregulation of RamA and/or RarA, respectively. One isolate demonstrated isolated overexpression of kpgA In conclusion, tigecycline-nonsusceptible K. pneumoniae bacteremia was associated with high mortality, and prior fluoroquinolone use was the independent risk factor for the acquisition of tigecycline-nonsusceptible K. pneumoniae The overexpression of AcrAB and/or OqxAB contributes to tigecycline nonsusceptibility in K. pneumoniae.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Risk Factors; Taiwan; Tigecycline; Transcription Factors

Non-typhoid Salmonella species represent a significant cause of aortitis. Few antimicrobial agents can be used when the patient is allergic or intolerable to cephalosporins or fluoroquinolones. Here, we report a case of bacteremia and aortitis caused by Salmonella enterica serotype Choleraesuis. This patient was cured by initial parenteral tigecycline and subsequent oral ciprofloxacin without surgical intervention.

Topics: Aged; Anti-Bacterial Agents; Aortitis; Bacteremia; Ciprofloxacin; Humans; Male; Minocycline; Salmonella arizonae; Salmonella enterica; Salmonella Infections; Tigecycline; Treatment Outcome

The spread of carbapenem-resistant gram negatives is a global emergency, and surveillance of new resistant clones is critical from both public health and clinical standpoints. Herein, we describe the emergence of a KPC-3-producing Escherichia coli ST69 as a cause of bloodstream infection in two Italian patients.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Gene Expression; Gentamicins; Humans; Italy; Male; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome

We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of those receiving other appropriate antimicrobial agents (13.8%, 9/65; P = 0.018). However, the percentages of end-stage renal disease and congestive heart failure were higher in the tigecycline cohort. The efficacy of tigecycline was contingent upon the illness severity and bacterial species. Tigecycline should be applied cautiously for treatment of Acinetobacter bacteremia.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Humans; Male; Minocycline; Tigecycline; Treatment Outcome

A 68-year-old male underwent a right hepatectomy, resection of the biliary convergence, and a left hepatic jejunostomy for a Klatskin tumour. The postoperative course was complicated by biliary abscesses with relapsing bloodstream infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). A 2-week course of combination antibiotic therapy failed to provide source control and the bacteraemia relapsed. Success was obtained with a regimen of tigecycline 100mg daily for 2 months, followed by tigecycline 50mg daily for 6 months, then 50mg every 48h for 3 months. No side effects were reported.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver; Male; Minocycline; Postoperative Complications; Tigecycline

Use of chlorhexidine and silver sulfadiazine-impregnated (CSS) central venous catheters (CVCs) has not been shown to decrease the catheter-related bloodstream infection rate in an ICU. The purpose of this study was to determine if use of minocycline and rifampin-impregnated (MR) CVCs would decrease central line-associated bloodstream infection (CLABSI) rates compared with those observed with use of CSS-impregnated CVCs.. A total of 7,181 patients were admitted to a 24-bed university hospital surgical ICU: 2,551 between March 2004 and August 2005 (period 1) and 4,630 between April 2006 and July 2008 (period 2). All patients requiring CVC placement in period 1 had a CSS catheter inserted, and in period 2 all patients had MR CVCs placed.. Twenty-two CLABSIs occurred during 7,732 catheter days (2.7 per 1,000 catheter days) in the 18-month period when CSS lines were used. After the introduction of MR CVCs, 21 catheter-related bloodstream infections occurred during 15,722 catheter days (1.4 per 1,000 catheter days). This represents a significant (p < 0.05) decrease in the CLABSI rate after introduction of MR CVCs. Mean length of time to infection developing after catheterization (8.6 days for CSS vs 6.1 days for MR) was also different (p = 0.04). The presence of MR did not alter the microbiologic profile of catheter-related infections, and it did not increase the incidence of resistant organisms.. The CLABSI rate decreased more with the use of MR CVCs compared with CSS CVCs in an ICU where the CLABSI rate was already low. The types of organisms causing infection were similar. With continued use of MR-impregnated CVCs in our ICU in the subsequent 5 years, we have seen sustained low rates of CLABSIs.

Topics: Academic Medical Centers; Anti-Infective Agents; Bacteremia; Catheter-Related Infections; Central Venous Catheters; Chlorhexidine; Female; Humans; Intensive Care Units; Male; Middle Aged; Minocycline; Rifampin; Silver Sulfadiazine; Treatment Outcome

Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient. The aim of this study was to determine the activity of ceftaroline and other antimicrobial agents against methicillin and linezolid-resistant Staphylococcus epidermidis.. We studied susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with clinical significance from an Intensive Care Unit, using E-test.. All strains were susceptible to the four antimicrobial agents, regardless of the level of resistance to linezolid.. Ceftaroline could be an alternative in the treatment of methicillin and linezolid-resistant S. epidermidis infections in critically ill patients.

Topics: Anti-Bacterial Agents; Bacteremia; Body Fluids; Catheter-Related Infections; Ceftaroline; Cephalosporins; Critical Care; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Exudates and Transudates; Humans; Linezolid; Methicillin; Minocycline; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline; Vancomycin

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as one of the most troublesome pathogens in healthcare settings worldwide. The present study was conducted to analyze the genes encoding resistance to carbapenems and to determine in vitro activity of colistin and tigecycline against CRAB isolates from blood culture of hospitalized patients at Istanbul University Cerrahpasa Medical School hospital.. Between January 2012 and June 2014, a total of 72 CRAB isolates were isolated by conventional methods from blood cultures of patients with bacteremia who were hospitalized in intensive care units and in various departments of the hospital. The isolates were confirmed using a Phoenix automated system. Antibiotic susceptibilities were determined by disk diffusion method and Etest. Molecular detection of resistance genes were screened by multiplex real time polymerase chain reaction (qPCR) and PCR parameters.. CRAB isolates were highly resistant to tetracycline (86.1%), trimethoprim/sulfamethoxazole (84.7%), ceftazidime (83.3%), cefepime (81.9%), ciprofloxacin (81.9%), amikacin (75.0%), piperacillin/tazobactam (75.0%), cefotaxime (72.2%), and gentamicin (69.4%). Tigecycline and colistin resistance were not detected. MIC50 and MIC90 of tigecycline (MIC ranges 0.016-1 µg/mL) and colistin (MIC ranges 0.125-1.5 µg/mL) were found to be 0.5 µg/mL and 1 µg/mL, respectively. All isolates were positive for OXA-51 that shows molecular identification of A. baumannii. Fifty-one (70.8%) and 2 (2.8%) of these isolates were positive for OXA-23 and OXA-58 genes, re- spectively.. This study indicated the most of the CRAB isolates in our hospital carry the OXA-23 gene. Colistin and tigecycline resistance were not detected. However, significant effort must be done to prevent the spread of OXA-23-producing CRAB-isolates and continuous monitoring of drug resistance is necessary in clinical settings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genotype; Hospitals, University; Humans; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Multiplex Polymerase Chain Reaction; Tigecycline; Turkey

Topics: Anti-Infective Agents; Bacteremia; Catheter-Related Infections; Female; Humans; Male; Minocycline; Rifampin

Topics: Anti-Infective Agents; Bacteremia; Catheter-Related Infections; Female; Humans; Male; Minocycline; Rifampin

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

Topics: Anti-Bacterial Agents; Antiviral Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Ceftazidime; Colectomy; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Ganciclovir; Humans; Immunosuppressive Agents; Intestine, Small; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir

Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection.

Topics: Adolescent; Anemia, Aplastic; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Catheter-Related Infections; Central Venous Catheters; Drug Administration Schedule; Female; Humans; Immunosuppressive Agents; Infant; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Tigecycline; Treatment Outcome

To investigate the spectrum and antimicrobial resistance of major pathogensthat causing nosocomial infections in China, 2013.. Nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 13 teaching hospital around China were collected. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The CLSI M100-S23 criteria were used for interpretation.. Of all cases, 1 022 cases were from BSI, 683 from HAP and 674 from IAI.Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI while Acinetobacter baumanii (34.6%) and Pseudomonas aeruginosa were dominated in HAP. Tigecycline, imipenem and meropenem exhibited high potency against Enterobacteriaceae and the susceptibilities rates were 95.6%, 94.2%and 95.2% respectively. Enterobacteriaceae demonstrated high resistance against cephalosporins (52.3%) and fluoroquinolones (38.9%) but were susceptible to β-lactam+inhibitor. Of all the Enterobacteriaceae, 30.5% were ESBLs positive and 4.3% were carbapenem resistant. Acinetobacter baumanii showed low susceptibilities to the microbial agents except for tigecycline (90.5%) and colistin (100%). The rate of carbapenem resistant Acinetobacter baumanii was 76.6%. Amikacin, ciprofloxacin, cefepime and piperacillin/tazobactam showed high antibacterial activity against Pseudomonas aeruginosa with susceptible rate 88.5%, 77.6%, 72.7% and 64.5% respectively. The resistant rate to imipenem and meropenem were 42.1% and 32.2%. All Staphylococcus aureus (166 strains) were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. MRSA accounted for 46.9% of all the Staphylococcus aureus. The prevalence of MRSA in IAI (55.2%) and HAP (54.4%) were higher that that in BSI (35.0%). No Enterococcus strains were found resistant to tigecycline, linezolid and daptomycin. VRE was found in Enterococcus faecium, accounting for 1.9% of all Enterococcus faecium strains.. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are the most common pathogens causing nosocomial infections. Nosocomial pathogens showed high susceptibilities against tigecycline. For ESBLs-producing Enterobacteriaceae strains, β-lactam+Inhibitor show high antibacterial activities. Vancomycin, teicoplanin and linezolid exhibit high potency to Staphylococcus aureus and Enterococcus.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefepime; Cephalosporins; China; Cross Infection; Hospitals, Teaching; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline; Vancomycin

Resistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline non-susceptible K. pneumoniae bacteremia.. Adult patients with tigecycline non-susceptible K. pneumoniae bacteremia at a medical center in Taiwan over a 3-year period were enrolled. K. pneumoniae isolates were identified by the E-test using criteria set by the US Food and Drug Administration (FDA). Data on the clinical features of patients were collected from medical records. Genes for β-lactamases, antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined for all isolates.. Of 36 patients, 27 had nosocomial bacteremia. Overall 28-day mortality was 38.9%. The MIC50 and MIC90 of tigecycline were 6 and 8 mg/L, respectively. No carbapenemase was detected among the 36 isolates. Twenty isolates carried extended spectrum β-lactamases and/or DHA-1 genes. No major cluster of isolates was found among the 36 isolates by PFGE. Intensive care unit onset of tigecycline non-susceptible Klebsiella pneumoniae bacteremia was the only independent risk factor for 28-day mortality.. The high mortality of patients with tigecycline non-susceptible K. pneumoniae bacteremia may suggest a critical problem. Further study to identify the possible risk factors for its development and further investigation of this type of bacteremia is necessary.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Retrospective Studies; Taiwan; Tigecycline

Combination therapy is recommended for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal regimen for colistin-resistant strains is unknown. We compared the synergistic activity and post-antibiotic effect (PAE) of colistin in combination with other antimicrobials against colistin-susceptible and -resistant KPC-Kp bloodstream isolates.. The genotypes of nine colistin-susceptible and eight colistin-resistant KPC-Kp bloodstream isolates were analysed using PCR and amplicon sequencing. Combinations of colistin, meropenem, tigecycline, rifampicin and teicoplanin were then screened using the Etest, a chequerboard assay and time-kill studies. Synergistic combinations were also analysed with respect to the PAE in time-kill curves and the PAE at clinically achievable concentrations.. Insertional inactivation of the PhoQ/PhoB two-component regulatory system by mgrB-IS5 was identified in 6/8 (75%) colistin-resistant KPC-Kp. Colistin/rifampicin combinations resulted in no interactions [fractional inhibitory concentration (FIC) indices 1.5-2] for colistin-susceptible strains, but were uniformly synergistic (FIC indices 0.1-0.4) against colistin-resistant KPC-Kp. Time-kill kinetic analysis, at clinically achievable fixed concentrations of rifampicin and colistin, confirmed synergy and produced persistent growth inhibition (3 h) of colistin-resistant KPC-Kp strains exposed to colistin/rifampicin or colistin/rifampicin/tigecycline combinations.. Combinations of colistin plus rifampicin, and less frequently tigecycline, exhibited synergistic activity in vitro against colistin-resistant KPC-Kp strains.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Drug Synergism; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; 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

Central venous catheters (CVC) removal and reinsertion of a new CVC in the setting of central line associated bloodstream infections (CLABSI) is not always possible in septic patients. The purpose of this study was to evaluate the outcome of patients with Staphylococcus aureus-CLABSI (SA-CLABSI) who had their CVCs exchanged over guidewire for minocycline/rifampin-coated (M/R)-CVC within seven days of bacteremia.. Each case was matched with two control patients who had SA-CLABSI and had their CVC removed within seven days and two control patients who had their CVC retained beyond seven days. In addition, an in vitro model was developed for exchange of catheters.. We identified 40 patients with SA-CLABSI. Eight patients had their CVC exchanged over guidewire with M/R-CVC and were compared to 16 patients who had their CVC removed and 16 other patients who had their CVC retained. Patients who had their CVC exchanged over guidewire had a similar clinical response and relapse rates compared to patients whose CVC was removed or retained. However the rate of overall mortality was higher in patients who retained their CVC compared to those whose CVC was exchanged or removed (p = 0.034). The in vitro catheter exchange model showed that catheter exchange over guidewire using M/R-CVC completely prevented biofilm colonization compared to exchange using uncoated CVC (p < 0.0001).. In the setting of SA-CLABSI, exchanging the CVC over guidewire with M/R-CVC could be an alternative to removing the CVC and reinserting another CVC at a different site and may be associated with a lower rate of overall mortality. Further large prospective randomized clinical trials are warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Catheterization, Central Venous; Central Venous Catheters; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Minocycline; Recurrence; Retrospective Studies; Rifampin; Staphylococcal Infections; Young Adult

Tigecycline is a semi-synthetic tetracycline with activity against most multidrug-resistant (MDR) bacteria.. We studied in vitro activity of tigecycline by agar dilution (AD) and Etest methods to evaluate their correlation. The study included 206 isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and MDR Acinetobacter baumannii recovered from blood cultures of patients of Baskent University between 2008 and 2010.. ESBL-producing E. coli had MIC50/MIC90 values of 0.5/0.5 µg/ml by AD and 0.25/0.5 µg/ml by Etest. ESBL-producing K. pneumoniae had MIC50/MIC90 values of 1/2 µg/ml by AD and 0.75/2 µg/ml by Etest, whereas MDR A. baumannii had MIC50/MIC90 values of 4/4 µg/ml by AD and 2/4 µg/ml by Etest. The correlation between AD and Etest was weak for ESBL-producing E. coli and strong for ESBL-producing K. pneumoniae and MDR A. baumannii. Tigecycline MIC values for ESBL-producing E. coli were lower than the tigecycline concentration, while they were higher than the concentrations attainable by treatment doses for A. baumannii.. Tigecycline is an appropriate agent in the treatment of E. coli bacteremia, but it is not for treating A. baumannii bacteremia. Tigecycline could be used for K. pneumoniae bacteremia treatment after determining its MIC value. Determining the MIC value by gold-standard methods is more appropriate due to the correlation between Etest and AD at high MIC values.

Topics: Agar; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10(8) CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Vaccines; Body Weight; Bronchopneumonia; Disease Models, Animal; Female; Imipenem; Immunization; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Reproducibility of Results; Tigecycline; Time Factors

This study investigates the clinical and epidemiological features of Chryseobacterium indologenes infections and antimicrobial susceptibilities of C indologenes.. With 215 C indologenes isolates between January 1, 2004 and September 30, 2011, at a medical center, we analyzed the relationship between the prevalence of C indologenes infections and total prescription of colistin and tigecycline, clinical manifestation, antibiotic susceptibility, and outcomes.. Colistin and tigecycline were introduced into clinical use at this medical center since August 2006. The increasing numbers of patients with C indologenes pneumonia and bacteremia correlated to increased consumption of colistin (p = 0.018) or tigecycline (p = 0.049). Among patients with bacteremia and pneumonia, the in-hospital mortality rate was 63.6% and 35.2% (p = 0.015), respectively. Administration of appropriate antibiotics showed significant benefit in 14-day survival in patients with C indologenes bloodstream infection (p = 0.040). In bacteremic patients, old cardiovascular accident (p = 0.036) and cancer (p = 0.014) were the most common comorbidity. The most common co-infection pathogen in patients with C indologenes pneumonia was Acinetobacter baumannii (36/91, 39.6%), followed by Pseudomonas aeruginosa (23/91, 25.3%), carbapenem-resistant A baumannii (22/91, 24.2%), and Klebseilla pneumoniae (13/91, 14.3%). Antimicrobial susceptibility testing of the 215 isolates showed that trimethoprim-sulfamethoxazole was the most active agent (susceptibility rate: 87.4%), followed by cefoperazone-sulbactam (48.0%).. The present study showed a trend of increasing prevalence of C indologenes infection after introduction of colistin and tigecycline usage. The bacteremia group had higher mortality rate than the pneumonia group. Increasing resistance to piperacillin-tazobactam, ceftazidime, cefepime, and newer fluoroquinolone were noticed in our analysis. Trimethoprim-sulfamethoxazole was a potential antimicrobial agent in vitro for C indologenes. To avoid collateral damage, we emphasize the importance of antibiotic stewardship program.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Colistin; Drug Prescriptions; Drug Resistance, Bacterial; Female; Flavobacteriaceae Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Prevalence; Survival Analysis; Tigecycline

Although tigecycline is considered one of the few therapeutic options for carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia, its role in the treatment of CRAB bacteraemia remains unclear. We describe the clinical outcomes of 9 patients who received tigecycline for CRAB bacteraemia. Although all CRAB blood isolates were susceptible to tigecycline, 5 (56%) deaths were related to CRAB bacteraemia and 1 case of breakthrough CRAB bacteraemia was observed during tigecycline therapy. Clinical outcomes of tigecycline therapy may be poor in patients with tigecycline-susceptible CRAB bacteraemia, although multiple factors including delayed treatment could contribute to the poor outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cohort Studies; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Catheter-related bloodstream infections very often involve the premature removal of long-term intravascular devices (LTID). The antibiotic lock therapy (ALT) represents a conservative approach to the treatment of uncomplicated infections of tunneled LTID when catheter removal is not a feasible option.. We present here the first reported case of tunneled LTID bloodstream infection due to a multidrug resistant Lactobacillus rhamnosus. The patient, who had large granular lymphocytic leukemia, was successfully treated with systemic tigecycline therapy and lock therapy.. Our results confirm ALT as a valid catheter-salvage strategy for the treatment of CRBSIs in clinically stable patients when catheter removal is not a feasible option, tigecycline appear to be a good option.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Drug Resistance, Multiple, Bacterial; Female; Gram-Positive Bacterial Infections; Humans; Lacticaseibacillus rhamnosus; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome

The emergence of colistin or tigecycline resistance as well as imipenem resistance in Acinetobacter baumannii poses a great therapeutic challenge. The bactericidal and synergistic effects of several combinations of antimicrobial agents against imipenem-, colistin- or tigecycline-resistant A. baumannii isolates were investigated by in vitro time-kill experiments. Six imipenem-resistant A. baumannii blood isolates were examined in this study, including colistin- and tigecycline-susceptible, colistin-resistant but tigecycline-susceptible, and colistin-susceptible but tigecycline-resistant isolates. Time-kill studies were performed using five antimicrobial agents singly or in combinations (imipenem plus colistin, imipenem plus ampicillin-sulbactam, colistin plus rifampicin, colistin plus tigecycline, and tigecycline plus rifampicin) at concentrations of 0.5× and 1× their MICs. Only imipenem was consistently effective as a single agent against all six A. baumannii isolates. Although the effectiveness of combinations of 0.5× MIC antimicrobial agents was inconsistent, combination regimens using 1× MIC of the antimicrobial agents displayed excellent bactericidal activities against all six A. baumannii isolates. Among the combinations of 0.5× MIC antimicrobial agents, the combination of colistin and tigecycline showed synergistic or bactericidal effects against four of the isolates. This in vitro time-kill analysis suggests that antimicrobial combinations are effective for killing imipenem-resistant A. baumannii isolates, even if they are simultaneously resistant to either colistin or tigecycline. However, the finding that the combinations of 0.5× MIC antimicrobial agents were effective on only some isolates may warrant further investigation of the doses of combination agents needed to kill resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Blood; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline; Time Factors

New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an experimental model of pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella pneumoniae. The susceptibilities of K. pneumoniae NDM, E. coli NDM and K. pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an experimental model of pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. pneumoniae NDM) and 37 (K. pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. pneumoniae NDM and K. pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. pneumoniae NDM and K. pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating pneumonia due to NDM-1-producing K. pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating experimental pneumonia due to NDM-1-producing E. coli and K. pneumoniae.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Bacterial Proteins; beta-Lactamases; Colistin; Disease Models, Animal; Drug Evaluation, Preclinical; Enterobacteriaceae Infections; Escherichia coli; Female; Klebsiella pneumoniae; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Tigecycline

Here we report on the antimicrobial resistance amongst Gram-negative isolates (excluding Acinetobacter spp.) collected from blood culture sources at European study sites as part of the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) from the study start in 2004 until August 2009. All isolates were collected and tested for minimum inhibitory concentrations using Clinical and Laboratory Standards Institute methodology. Over the collection period, extended-spectrum β-lactamase (ESBL) production was recorded in 21.1% of Klebsiella pneumoniae, 2.6% of Klebsiella oxytoca and 11.3% of Escherichia coli, primarily in Croatia, Greece, Hungary, Italy, Poland, Romania and the Slovak Republic. ESBL rates stabilised amongst K. pneumoniae over 2006-2009, but doubled amongst E. coli in 2008-2009. The patterns of antimicrobial resistance changed accordingly for both organisms. Generally, Greece had the highest antimicrobial resistance for K. pneumoniae, Italy for E. coli, Serratia marcescens and Enterobacter spp., and Croatia for Pseudomonas aeruginosa. High resistance rates amongst K. pneumoniae were also seen in Croatia and Italy. Imipenem resistance amongst K. pneumoniae was reported exclusively in Greece (13.8%); amongst other Enterobacteriaceae, imipenem resistance was absent or low. Similarly, meropenem resistance was low amongst the Enterobacteriaceae except K. pneumoniae from Greece (42.6%). Across Europe, the most active antimicrobial agents against the Enterobacteriaceae were tigecycline, amikacin and the carbapenems, each with <10% resistance each year. Against the other antimicrobials, significant increases in non-susceptibility were reported for K. pneumoniae and E. coli, both important causative pathogens of bacteraemia.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Blood; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

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

We investigated the clinical characteristics and outcomes of 43 patients with Acinetobacter junii bacteremia at a 2,500-bed tertiary care center in northern Taiwan. These organisms were confirmed to the species level by an array assay and 16S rRNA gene sequence analysis. The antimicrobial susceptibilities of the 43 A. junii isolates to 13 agents were determined using the agar dilution method. Susceptibility testing for tigecycline was determined using the broth microdilution method. Most of the patients were hospital-acquired (n = 36, 83.7 %) or healthcare facility-related infections (n = 6, 13.9 %), and 55.8 % had impaired immunity. Central venous access devices were present in 35 (81.4 %) patients; among the total of 43 patients with A. junii bacteremia, 8 patients were diagnosed as catheter-related bloodstream infection and 19 patients were diagnosed as catheter-associated bloodstream infection. Shock requiring inotropic agents occurred in 2 patients (4.6 %). Most patients developed bacteremia in general wards (n = 36, 83.7 %). The overall in-hospital mortality rate was low (7 %), despite the low rate of removal of central venous devices, low rate of holding usage of original central venous devices, and high rate of inappropriate antimicrobial regimens. Carbapenems, fluoroquinolones, and amikacin had potent activity (>95 % susceptible rate) against A. junii isolates. Interestingly, 35 % of the A. junii isolates were resistant to colistin. Tigecycline exhibited low minimum inhibitory concentration (MIC) values (range, 0.06-2 μg/ml, MIC(90), 1 μg/ml) against the A. junii isolates.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Carbapenems; Catheter-Related Infections; Central Venous Catheters; Colony Count, Microbial; Cross Infection; Drug Resistance, Bacterial; Female; Hospital Mortality; Humans; Incidence; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; RNA, Ribosomal, 16S; Sequence Analysis, RNA; Taiwan; Tertiary Care Centers; Tigecycline

This study was designed to evaluate antimicrobial activities against methicillin-susceptible Staphylococcus aureus in both sessile and planktonic forms and to detect genes associated with this biofilm phenotype. Minimal biofilm inhibition and eradication concentrations (MBIC and MBEC, respectively) were determined by an in vitro biofilm model, and icaA, atlA, and sasG genes were detected by polymerase chain reaction. Vancomycin and tigecycline presented better biofilm inhibitory activity (MBIC range: 4-8 μg/mL) (P ≤ 0.05) and lower MBEC/MIC ratios (P ≤ 0.001) than other antimicrobials. All isolates harbored icaA and atlA, whereas sasG was present only in strong biofilm formers (P ≤ 0.05). Interestingly, antimicrobial activities against sasG- weak biofilm formers were significantly higher than those against sasG+ strong biofilm formers (P ≤ 0.05), demonstrating that number of cells in a biofilm matrix affected the antimicrobial activity, which was also variable, and might be associated with specific genetic determinants. To our knowledge, this was the first study reporting the presence of sasG in clinical isolates of S. aureus in South America.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Biofilms; Brazil; Catheter-Related Infections; Humans; Membrane Proteins; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Bacteremia; Diverticulitis; Female; Humans; Minocycline; Tigecycline; Tomography, X-Ray Computed

Catheters coated with minocycline and rifampin are proven to decrease the rates of central line-associated bloodstream infection; however, it is unclear whether success occurs independent of other infection control precautions. We evaluated the effect of catheters coated with minocycline and rifampin with and without other infection control precautions on our rates of central line-associated bloodstream infection in critically ill patients and on antibiotic resistance throughout the hospital and in the intensive care unit.. Retrospective clinical cohort study conducted during 1999-2006 with an observational laboratory component.. A tertiary university-based cancer center.. All 8009 patients admitted to the medical intensive care unit were subjects for the surveillance of central line-associated bloodstream infection. All Staphylococcus aureus and coagulase-negative staphylococci clinical isolates cultured at our institution during the same period were subjects for laboratory testing.. Using catheters coated with minocycline and rifampin and implementing infection control precautions.. Incidence of central line-associated bloodstream infection in the medical intensive care unit. Change in resistance to tetracycline and rifampin in clinically relevant staphylococcal isolates in the intensive care unit and hospitalwide. During the study period, 9200 catheters coated with minocycline and rifampin were used hospitalwide over a total of 511,520 catheter days. The incidence of central line-associated bloodstream infection per 1000 patient days in the medical intensive care unit significantly and gradually decreased from 8.3 in 1998 to 1.2 in 2006 (p ≤ .001). The resistance of S. aureus and coagulase negative staphylococci clinical isolates to tetracycline or rifampin in the intensive care unit and on a hospitalwide level remained stable or decreased significantly during the same period.. Catheters coated with minocycline and rifampin significantly decreased the incidence of central line-associated bloodstream infection in the medical intensive care unit in a manner that was independent and complementary to the infection control precautions. Although this study strongly suggests an association between catheters coated with minocycline and rifampin use and a decrease in central line-associated bloodstream infection, because of multiple other concurrent interventions, the results should be interpreted cautiously until a prospective study is conducted. Furthermore, long-term use of these devices is not associated with increased resistance of staphylococcal isolates to tetracycline and rifampin in the intensive care unit or throughout the hospital.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Blood-Borne Pathogens; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Chi-Square Distribution; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance, Multiple, Bacterial; Female; Follow-Up Studies; Humans; Infection Control; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Retrospective Studies; Rifampin; Risk Assessment; Statistics, Nonparametric; Time Factors; Treatment Outcome

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is an emerging multidrug-resistant nosocomial pathogen. This is a retrospective chart review describing the outcomes and treatment of 60 cases of CR-Kp bloodstream infections. All CR-Kp isolated from blood cultures were identified retrospectively from the microbiology laboratory from January 2007 to May 2009. Clinical information was collected from the electronic medical record. Patients with 14-day hospital mortality were compared to those who survived 14 days. The all-cause in-hospital and 14-day mortality for all 60 CR-Kp bloodstream infections were 58.3% and 41.7%, respectively. In this collection, 98% of tested isolates were susceptible in vitro to tigecycline compared to 86% to colistimethate, 45% to amikacin, and 22% to gentamicin. Nine patients died before cultures were finalized and received no therapy active against CR-Kp. In the remaining 51 patients, those who survived to day 14 (n = 35) were compared to nonsurvivors at day 14 (n=16). These patients were characterized by both chronic disease and acute illness. The 90-day readmission rate for hospital survivors was 72%. Time to active therapy was not significantly different between survivors and nonsurvivors, and hospital mortality was also similar regardless of therapy chosen. Pitt bacteremia score was the only significant factor associated with mortality in Cox regression analysis. In summary, CR-Kp bloodstream infections occur in patients who are chronically and acutely ill. They are associated with high 14-day mortality and poor outcomes regardless of tigecycline or other treatment regimens selected.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prognosis; Retrospective Studies; Tigecycline; Treatment Outcome

The recent molecular epidemiological studies concerning epidemiological studies concerning methicillin-resistant Staphylococcus aureus (MRSA) blood isolates from adult patients and susceptibilities of MRSA isolates with high vancomycin minimum inhibitory concentrations (MICs) (≥2 mg/L) to linezolid, tigecycline, and daptomycin in Taiwan remain limited. The objectives of the study were (1) to better understand the change of molecular epidemiology of MRSA blood isolates and (2) to evaluate the in vitro activity of new anti-Gram-positive agents, including linezolid, tigecycline, and daptomycin.. A total of 470 nonduplicate MRSA blood isolates from adult patients (older than 18 years) were collected from January 2006 to December 2008. The MICs of these isolates to various antibiotics were determined. Multilocus sequence typing was also performed in all isolates.. Three sequence types (STs) constitute most (92.1%) of these 470 MRSA isolates: ST239 (53.2%), ST59 (23.2%), and ST5 (15.7%). Throughout the 3-year study, the ST239 strain remained predominant but with a significant trend of declining annually (p=0.03). In contrast, the proportion of isolates of ST59 increased, although the increment was insignificant (p=0.14). The proportion of MRSA isolates with a vancomycin MIC of 2 mg/L was 17.2%. All of these isolates with a vancomycin MIC of 2 mg/L were susceptible to linezolid and tigecycline, whereas most of them (98.8%) were susceptible to daptomycin.. ST239 remained predominant during the 3-year period but with a significant trend of declining. Moreover, linezolid, tigecycline, and daptomycin remained highly active against MRSA blood isolates, even with a vancomycin MIC of 2 mg/L.

Topics: Acetamides; Adult; Anti-Bacterial Agents; Bacteremia; Blood; Daptomycin; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Taiwan; Tigecycline; Vancomycin

Topics: Aged, 80 and over; Bacteremia; Daptomycin; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Tigecycline; Vancomycin Resistance

To investigate the clinical implication and prognostic predictors of tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii (MDRAB).. A retrospective observational study over a 32-month period for adult patients receiving tigecycline treatment at least 7 days for pneumonia involving MDRAB.. We reviewed 112 patients with 116 episodes of tigecycline-treated pneumonia involving MDRAB. The mean age was 70.8 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.7. Seventy episodes (60.3%) had clinical resolution. The episodes with monomicrobial MDRAB pneumonia had a significantly lower clinical resolution rate than polymicrobial pneumonia (14/31, 45.2% vs. 56/85, 65.9%; p = 0.044). The independent predictors for failure of clinical resolution were female gender, malignancy, bilateral pneumonia, monomicrobial pneumonia, and higher APHCHE II scores. Forty-two episodes (36.2%) had the 30-day mortality, and the only independent predictor was deterioration of pneumonia on chest radiographs.. A high disease severity, bilateral pneumonia, and monomicrobial MDRAB pneumonia predicted failure of clinical resolution, and deterioration of pneumonia predicted mortality. MDRAB in monomicrobial pneumonia was the most certain to be causal. The clinical resolution rate from such pneumonia might reflect the ultimate efficacy of tigecycline in treating MDRAB pneumonia and the overall efficacy might be overestimated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacteremia; Demography; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Prognosis; Retrospective Studies; Severity of Illness Index; Sex Factors; Tigecycline; Treatment Outcome

Topics: Bacteremia; beta-Lactamases; Calciphylaxis; Coinfection; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; Minocycline; Tigecycline

Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health.. The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years.. Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis.. The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.

Topics: Anti-Bacterial Agents; Bacteremia; Cardiovascular Diseases; Chronic Periodontitis; Dental Scaling; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Glycated Hemoglobin; Humans; Hypertension; Japan; Middle Aged; Minocycline; Myocardial Infarction; Periodontal Abscess; Porphyromonas gingivalis; Risk Factors; Syndrome; Tooth Extraction

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Female; Humans; Male; Minocycline

Topics: Anti-Bacterial Agents; Bacteremia; Cardiovascular Diseases; Conscious Sedation; Crowns; Dental Implants; Dental Scaling; Gingivitis; Humans; Inflammation Mediators; Minocycline; Periodontitis; Probiotics; Risk Assessment; Thrombosis; Tooth Loss; United States

Topics: Anti-Bacterial Agents; Bacteremia; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The spread of antimicrobial resistance among members of the Enterobacteriaceae is a significant clinical threat. We report the treatment of pan-resistant Klebsiella pneumoniae bacteraemia with combination tigecycline and colistin in a 49-year-old male and review available therapeutic options. Despite a poor prognosis, the patient recovered, but remains colonized with the pan-resistant isolate.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; Data Interpretation, Statistical; Humans; Minocycline; Tigecycline; Treatment Outcome

This study evaluated vancomycin susceptibility and activity alone and in combination with rifampicin and tigecycline against low-biofilm- and high-biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates.. Forty MRSA isolates recovered from bloodstream infections were analysed. Susceptibilities were performed in planktonic and biofilm cultures by microbroth dilution. Biofilm production was determined using an adherent plate assay. Time-kill analysis was performed on six low- and six high-biofilm-producing isolates with 15 mg/L vancomycin alone and in combination with rifampicin or tigecycline at 4x MIC.. Vancomycin susceptibility displayed a 4-fold and an 8-fold increase in the MIC(50) and MIC(90), respectively, in the presence of biofilm. Rifampicin and tigecycline susceptibilities also increased in biofilms, but still remained within the susceptibility breakpoints except for a tigecycline MIC(90) of 1 mg/L. High biofilm production was detected in 60% of the isolates. In time-kill analysis, 15 mg/L vancomycin achieved bactericidal activity against only low-biofilm-producing strains with a 1.8 log(10) cfu/mL difference in bacterial kill compared with high-biofilm-producing strains (P < 0.001). Rifampicin alone had minimal activity, resulting in resistance. Tigecycline was minimally effective and was not bactericidal, but no difference was observed in the comparison of biofilm-producing strains. Vancomycin in combination with rifampicin or tigecycline was bactericidal against all strains (mean kill 4.5 +/- 0.5 log(10) cfu/mL), regardless of biofilm production.. Vancomycin exposures at 15 mg/L may not be adequate in eradicating biofilm-producing S. aureus. Alternative treatments or combination therapy should be explored to optimize outcomes in biofilm-associated infections.

Topics: Anti-Bacterial Agents; Bacteremia; Biofilms; Colony Count, Microbial; Drug Synergism; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Rifampin; Staphylococcal Infections; Tigecycline; Vancomycin

Antimicrobial resistance in Salmonella spp. is of grave concern, more so in quinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing isolates that cause complicated infections. The MIC of azithromycin, ciprofloxacin, cefixime, cefepime, ceftriaxone, gatifloxacin, imipenem, levofloxacin, meropenem and ofloxacin (E-test strip) and tigecycline and faropenem (agar dilution) against 210 Salmonella spp. was determined. MIC(90) (defined as the antimicrobial concentration that inhibited growth of 90 % of the strains) of the carbapenems (imipenem and meropenem) for Salmonella Typhi and Salmonella Paratyphi A was 0.064 microg ml(-1). MIC(90) of faropenem was 0.25 microg ml(-1) for S. Typhi, S. Paratyphi A and Salmonella Typhimurium. The MIC(90) of azithromycin for all Salmonella spp. ranged from 8 to 16 microg ml(-1). Tigecycline showed an MIC(90) of 2 microg ml(-1) for S. Typhi, 1 microg ml(-1) for S. Paratyphi A and 4 microg ml(-1) for S. Typhimurium. We concluded that tigecycline and the carbapenems are likely to have roles in the final stage of treatment of quinolone-resistant and ESBL-producing multidrug-resistant salmonellae.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Quinolones; Salmonella; Salmonella Infections; Tigecycline; Typhoid Fever

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Blood; Chryseobacterium; Colistin; Flavobacteriaceae Infections; Humans; Infant; Infant, Newborn; Minocycline; Taiwan; Tigecycline; Young Adult

This observational retrospective study aims to present early experience with tigecycline (TIG) in the treatment of infections due to multi-drug resistant (MDR) microorganisms.. Adult patients included, received TIG for >5 days either as monotherapy (M group) or as presumed active monotherapy (PAM group). In the PAM group, all co-administered antimicrobial(s) were resistant in vitro against the targeted pathogen(s) or had been clinically and microbiologically failing after >or=5 days of therapy despite in vitro susceptibility.. Forty-five patients (35 in ICU) were treated for 28 Acinetobacter baumannii and 23 Klebsiella pneumoniae infections [21 ventilator-associated and healthcare-acquired pneumonia (VAP/HCAP), 10 bloodstream infections (BSI) and 14 surgical infections (SI)]. Successful overall clinical outcome was 80%, i.e. 81.8% in M group, 78.3% in PAM group, 90.5% in VAP/HCAP, 80% in BSI, 64.3% in SI and 85% in the cases with septic shock. Superinfections from Enterobacteriaceae inherently resistant to tigecycline occurred in 31.8% of M and 13% of PAM group (p<0.001).. TIG represents a promising option in infections from MDR pathogens, however, further clinical experience is required.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Analysis of Variance; Anti-Bacterial Agents; Bacteremia; Chi-Square Distribution; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Shock, Septic; Surgical Wound Infection; Tigecycline

Tigecycline, the first in a new class of glycylcyclines, has been approved for the treatment of complicated skin and skin structure and intraabdominal infections in adults. However, clinical data on its safety and effectiveness in cancer patients are lacking. We reviewed the records of all cancer patients treated with tigecycline for more than 48 hours between June 2005 and September 2006 at our institution and identified 110 consecutive cases (median age, 58 yr; range, 18-81 yr). We collected data on demographics, cancer type, tigecycline indication, microbiologic characteristics, side effects, and outcome. Sixty-four (58%) patients had hematologic malignancies; 27 patients had undergone hematopoietic stem cell transplantation. Thirty-one (28%) patients had neutropenia, and 62 (56%) were in the intensive care unit at the start of therapy. Most patients (106 [96%]) received tigecycline as a second-line agent (after not responding to other broad-spectrum antibiotics), and 101 (92%) received it in combination with an antipseudomonal drug. The mean duration of therapy was 11 days (range, 3-35 d). Sixty-six (60%) patients received tigecycline for refractory pneumonia, 19 (17%) had bacteremia, 9 (8%) had intraabdominal infections, and 7 (6%) had complicated skin and soft tissue infections. Fifty (45%) patients had microbiologically documented infections, and the remaining patients had negative cultures at the start of therapy.An overall clinical response was noted in 70 (64%) patients. More clinical responses were seen in patients with bacteremia than in those with pneumonia (79% vs. 51%; p = 0.029). Patients with microbiologically documented infections had significantly higher clinical response rates than patients with non-microbiologically documented infections (73% vs. 55%; p = 0.047). Forty (36%) patients did not respond to treatment; 36 of these patients died of active infection during tigecycline therapy. Patients with pneumonia had a significantly higher mortality rate than patients with bacteremia (44% vs. 16%; p = 0.026). During the 60 days of follow-up from the date of clinical response, patients with pneumonia had significantly shorter survival durations than patients with other infections. Of the 42 patients who were not on antiemetics or ventilator support at the start of tigecycline therapy, 2 (5%) experienced mild nausea, and 1 (2%) experienced nausea and vomiting. Only 4 (4%) patients overall experienced diarrhea during tigecycline therapy, all

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Female; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Leukemia; Lymphoma; Male; Middle Aged; Minocycline; Nausea; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome; Vomiting; Young Adult

Acinetobacter infections resistant to multiple classes of antibiotics have become prevalent in many institutions. Tigecycline has in vitro activity against Acinetobacter spp. and has been suggested as a therapeutic option in these infections.. To describe the clinical and microbiologic outcomes of patients who received tigecycline for the treatment of infections caused by Acinetobacter spp. at our institution.. A retrospective review was conducted of the medical records of 29 sequential patients who received tigecycline for treatment of Acinetobacter infections. The outcomes assessed for efficacy were clinical improvement or cure and microbiologic cure in evaluable patients.. Patients received tigecycline a median of 30 days into hospitalization for a median of 11 days. Common indications were pneumonia (15 pts.), bacteremia (6), and urinary tract infection (3). Positive clinical outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of the 25 microbiologically evaluable patients, 11 (44%) had resolution of their cultures. Eleven patients had susceptibility testing performed, and the median minimum inhibitory concentration was 4 microg/mL (range 3-8).. In this case series, most patients did not have clinically or microbiologically favorable outcomes with tigecycline therapy. No patient had an isolate that was fully susceptible to tigecycline. Data from more studies are needed before tigecycline can be recommended for the treatment of Acinetobacter infections.

Topics: Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bronchitis; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Urinary Tract Infections; Wound Infection

Topics: Asepsis; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Chlorhexidine; Cross Infection; Equipment Contamination; Humans; Minocycline; Rifampin; Silver Sulfadiazine

We report the use of tigecycline, firstly with colistin and finally alone, in a patient with a persistent breakthrough bacteremia due to a Klebsiella pneumoniae isolate harboring a metallo-beta-lactamase (VIM-1) and an extended-spectrum beta-lactamase (SHV-12). Time-kill studies demonstrated that the combination of both compounds was synergistic along the first 12 h, suppressing the regrowth observed after 3 to 6 h when colistin was tested alone.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Drug Synergism; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Minocycline; Tigecycline

In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Biofilms; Catheterization, Central Venous; Daptomycin; Humans; Linezolid; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcus aureus; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Aged; Anti-Bacterial Agents; Bacteremia; Calcaneus; Colistin; Humans; Male; Microbial Sensitivity Tests; Osteomyelitis

Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed.. The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor.. Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively.. To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.

Topics: Acinetobacter baumannii; Aged; Anti-Bacterial Agents; Bacteremia; Dipeptides; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

A patient genetically diagnosed with X-linked agammaglobulinemia repeatedly developed bacteremia due to Campylobacter coli (C. coli) for one year and seven months in spite of immunoglobulin replacement therapy. Throughout the clinical course, C. coli with identical genetic patterns was repeatedly isolated from both blood and stool cultures, thus indicating that the patient had latent intestinal infection. The bacteremia was always accompanied by reactive arthritis. Since the immunoglobulin level was extremely low with severe B cell deficiency, the reactive arthritis must have been induced in a humoral immunity-independent manner. Adding oral minocycline following intravenous meropenem was very effective; the stool cultures became negative and the patient has been well for more than one year without relapse of bacteremia.

Topics: Administration, Oral; Adult; Agammaglobulinemia; Anti-Bacterial Agents; Arthritis, Reactive; Bacteremia; Campylobacter coli; Campylobacter Infections; Chromosomes, Human, X; Feces; Genetic Linkage; Humans; Injections, Intravenous; Intestinal Diseases; Male; Meropenem; Minocycline; Recurrence; Thienamycins; Treatment Outcome

We assessed the in vitro effect of exposing various bacteria to minocycline/rifampicin-impregnated vascular catheters on the antimicrobial activity of the catheters and the antimicrobial susceptibility of tested organisms.. Segments of minocycline/rifampicin-impregnated catheters were placed in agar plates inoculated with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus (VRE). Zones of inhibition were measured at 24 h, and colonies from the edge of this zone were retrieved after 72 h and inoculated onto new agar plates. A total of seven 72 h cycles were completed. We then measured the MICs of minocycline, rifampicin, vancomycin and linezolid for the collected strains.. The zones of inhibition of the four organisms remained stable after 21 days of sequential exposure to the impregnated catheters. The MICs of the antimicrobials remained constant, except for the MICs of rifampicin for MRSA and linezolid for MRSE, which increased slightly but remained within the susceptible range.. Minocycline/rifampicin-impregnated catheters remain effective against MSSA, MRSA, MRSE and VRE, as evidenced by stable zones of inhibition following 21 day sequential exposure to these catheters. The increase in MIC of rifampicin for MRSA may be clinically relevant if the catheter remains in place for >12 days though the strain remained susceptible to minocycline, there was no concurrent increase in the MIC of other tested drugs, and the zones of inhibition remained stable.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Drug Resistance, Bacterial; Equipment Contamination; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Minocycline; Rifampin; Time Factors

To evaluate early experience with tigecycline alone or in combination with other antimicrobials for treatment of ventilator-associated pneumonia (VAP) and/or bacteremia caused by multidrug-resistant Acinetobacter baumannii.. Retrospective case series.. University-affiliated medical center.. Twenty-five patients with multidrug-resistant A. baumannii who received tigecycline for VAP (19 patients), bacteremia (3), or VAP plus bacteremia (3) between September 1, 2005, and May 31, 2006. Five patients were treated with tigecycline alone.. Primary outcomes were resolution of clinical signs and symptoms of the infection and documented microbial eradication of A. baumannii with tigecycline. Overall, 21 (84%) of the 25 patients had clinical resolution. Four had clinical failure: three with VAP and one with VAP plus bacteremia that developed resistance to tigecycline during therapy. Microbial eradication was demonstrated in 12 (80%) of 15 patients in whom repeat cultures were obtained. Three patients with VAP had a recurrence of infection: one patient had two recurrences, and two patients had one recurrence each. All four recurrent episodes led to clinical resolution and microbial eradication. No patients discontinued tigecycline because of adverse events.. Tigecycline was effective in most of these 25 patients when used alone or in combination with other antimicrobials for VAP and/or bacteremia caused by multidrug-resistant A. baumannii. The emergence of a resistant strain while one patient was receiving therapy, however, is concerning.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline

Multi-resistant coagulase-negative staphylococci (CNS) may cause systemic infections in patients undergoing bone marrow transplantation. Daptomycin, a new lipopeptide, and tigecycline, a new glycylcycline, have excellent activity against Gram-positive bacteria including methicillin-resistant staphylococci. This study presents the in vitro activity of daptomycin and tigecycline compared to vancomycin and fosfomycin against 105 CNS isolated from 76 bone marrow transplant patients with symptomatic bacteremia.. Blood stream isolates of Staphylococcus epidermidis (n = 102) and Staphylococcus haemolyticus (n = 3) from bone marrow transplant patients were collected from 2000 to 2006. The susceptibility of all isolates was tested using methods of the Clinical Laboratory Standards Institute.. The minimal inhibitory concentrations MIC(50) and MIC(90) were 0.125 microg/mL and 0.25 microg/mL for daptomycin, 0.25 and 0.5 microg/mL for tigecycline, 1 microg/mL and 2 microg/mL for vancomycin, and 8 microg/mL and >256 microg/mL for fosfomycin, respectively. MIC values of tested agents were similar for both methicillin-sensitive and methicillin-resistant S. epidermidis strains.. All CNS isolates were susceptible to the new antistaphylococcal agents daptomycin and tigecycline. Although vancomycin had been used over the past 30 yr at our bone marrow transplant unit all CNS were still susceptible to vancomycin.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bone Marrow Transplantation; Coagulase; Daptomycin; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Hematologic Neoplasms; Humans; In Vitro Techniques; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Staphylococcus haemolyticus; Tigecycline; Vancomycin

Catheter-associated bloodstream infections (CABSI) are among the most common and serious adverse events experienced by critically ill children. Randomized trials have demonstrated that the use of central venous catheters (CVC) coated with antiseptic solutions reduces rates of CABSI in adult patients; however, their efficacy in children has not been evaluated.. To compare the incidence of CABSI, rate of complications, and microbiology of infection in critically ill children treated with antibiotic-coated or noncoated CVC (NC-CVC).. A prospective observational trial was conducted in the pediatric intensive care unit (PICU) during a 13-month period. A minocycline-rifampin-coated CVC (MR-CVC) or NC-CVC was placed by PICU physicians who nonpreferentially selected CVC type.. We studied the outcomes associated with the first CVC placed in 225 patients, including 69 MR-CVC and 156 NC-CVC. Patients who received MR-CVC, as compared with NC-CVC, were similar in gender, age, and severity of illness at time of PICU admission. The incidence density of CABSI did not vary by catheter type [MR-CVC: 7.53 per 1000 catheter-days (95% confidence interval 2.05-19.17); NC-CVC: 8.64 CABSI per 1000 catheter-days (95% confidence interval 3.74-16.96)]. However, the median time to infection in children with MR-CVC was 3-fold longer than in children with NC-CVC [18 versus 5 days (P = 0.053)]. No difference was seen in the incidence of complications, including thrombosis and catheter site reaction, between MR- and NC-CVC. No significant difference was observed in the types of organisms recovered from patients with MR- and NC-CVC.. The use of MR-CVC significantly delayed the onset of CABSI in PICU patients. Larger, randomized trials are needed to better define potential differences in the incidence of CABSI, rate of complications, and microbiology of infection among pediatric patients treated with antiseptic-coated CVC and NC-CVC.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacteremia; Blood; Catheterization, Central Venous; Child; Child, Preschool; Female; Humans; Intensive Care Units, Pediatric; Male; Medical Records; Minocycline; Philadelphia; Rifampin; Survival Analysis; Treatment Outcome

Topics: Anti-Infective Agents, Local; Bacteremia; Carbon; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Equipment Contamination; Humans; Minocycline; Platinum; Rifampin; Silver

We report 4 cases of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections who received treatment with tigecycline after unsuccessful treatment attempts with conventional drugs. All 4 patients were eventually cured although 1 experienced a relapse of her bacteremia while on treatment due to inadequate dosing.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Methicillin Resistance; Middle Aged; Minocycline; Recurrence; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Treatment Outcome

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Catheter-related bloodstream infections are costly and associated with substantial morbidity and mortality. Trials suggest that central venous catheters impregnated with minocycline/rifampin, although more expensive, are clinically superior to chlorhexidine/silver sulfadiazine impregnated catheters. It remains unclear whether minocycline/rifampin catheters are cost-effective for all high-risk patients or only those requiring longer-term catheterization.. We developed a series of decision models with patient-level clinical trial data to determine whether minocycline/rifampin catheters are cost-effective for patients requiring various durations of catheterization. We calculated incremental cost-effectiveness ratios for patients catheterized for durations ranging from 1 to 25 days.. The data were too sparse to estimate cost-effectiveness for patients catheterized less than 8 days. The probability that minocycline/rifampin catheters were cost-effective compared with chlorhexidine/silver sulfadiazine catheters in patients catheterized for 8 days was 91%. The probability that the minocycline/rifampin catheters in patients catheterized 13 days or longer resulted in cost savings was more than 95%.. Our analysis suggests that central venous catheters coated with minocycline/rifampin are cost-effective for patients catheterized for at least 1 week and lead to overall cost savings when patients are catheterized for 2 weeks or longer. Policies for the use of antimicrobial catheters in high-risk patients should reflect patients' expected duration of catheterization.

Topics: Anti-Infective Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Chlorhexidine; Cost-Benefit Analysis; Decision Support Techniques; Drug Delivery Systems; Humans; Middle Aged; Minocycline; Quality-Adjusted Life Years; Rifampin; Sensitivity and Specificity; Silver Sulfadiazine; Time Factors; United States

To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU.. Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999).. ICUs of a tertiary care hospital in Houston, TX.. Cancer patients in the medical ICU (MICU) and surgical ICU (SICU).. ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999.. The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999.. The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cause of Death; Child; Child, Preschool; Coated Materials, Biocompatible; Critical Care; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Enterococcus; Female; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Opportunistic Infections; Prospective Studies; Rifampin; Survival Rate; Texas; Vancomycin Resistance

To determine the efficacy of antibiotic catheter lock solution in preventing catheter-related infections, silicone catheters were tunneled and inserted into the jugular veins of 18 rabbits. The catheters were challenged with an intraluminal injection of 10(5) CFU of slime-producing Staphylococcus epidermidis in 0.1 ml of water. The catheters were maintained on heparin (100 IU/ml) flush for the first 3 days. On day 3, quantitative blood samples for culture were obtained from the catheters and ear veins, which documented catheter-related bacteremia, and the rabbits were randomized to have their catheters flushed as follows: five animals were continued on heparin (100 IU/ml), five animals received vancomycin (3 mg/ml) with heparin (100 IU/ml), and eight animals received 3 mg of minocycline per ml with 30 mg of EDTA per ml (M-EDTA). All animals were killed at day 7. Blood, catheters, jugular veins, and heart valves were cultured quantitatively. Animals maintained on heparin developed catheter-related colonization, bacteremia, septic phlebitis, and endocarditis. Vancomycin-heparin partially prevented catheter colonization, bacteremia, and phlebitis (P = 0.2). M-EDTA completely prevented catheter colonization, catheter-related bacteremia, and phlebitis in all of the animals (P < 0.01). Tricuspid endocarditis was equally prevented by vancomycin-heparin and M-EDTA (P < or = 0.06). In conclusion, the M-EDTA catheter flush solution was highly efficacious in preventing catheter-related colonization, bacteremia, septic phlebitis, and endocarditis in rabbits.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Catheterization; Disease Models, Animal; Edetic Acid; Endocarditis; Male; Minocycline; Phlebitis; Prosthesis-Related Infections; Rabbits

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteremia; Catheterization, Central Venous; Chlorhexidine; Equipment Contamination; Humans; Minocycline; Rifampin; Silver Sulfadiazine

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteremia; Bacteria; Catheterization, Central Venous; Chlorhexidine; Equipment Contamination; Humans; Minocycline; Rifampin; Silver Sulfadiazine

Actinomycosis is an uncommon infectious disease caused predominantly by Actinomyces israelii. The cutaneous disseminated form is usually caused by hematogenous dissemination from a primary extra-cutaneous lesion. We report here cutaneous disseminated actinomycosis without any detectable extra-cutaneous lesions in a 42-year-old Japanese woman with acute lymphocytic leukemia. Multiple soft nodules developed on her upper and lower extremities. Histopathological examination revealed "sulfur granules", which are a specific finding for actinomycosis. Cultures from biopsy specimens were not successful. There were no cervicofacial, thoracic, nor abdominal lesions. These findings suggest that cutaneous disseminated actinomycosis in our patient developed primarily in the skin. Although the patient was immunocompromised, antibiotic treatment with minocycline was effective.

Topics: Actinobacillus; Actinomycosis; Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Arm; Bacteremia; Biopsy; Cytoplasmic Granules; Female; Humans; Immunocompromised Host; Leg Dermatoses; Minocycline; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Skin Diseases, Bacterial

Three patients with recurrent vascular catheter-related bacteremia were successfully treated by allowing a solution of minocycline and ethylenediaminetetraacetate (EDTA) to dwell in the lumen of the indwelling catheter or by coating polyurethane catheters with minocycline/EDTA and flushing the lumen daily with the same solution. In vitro and in vivo experiments showed that minocycline/EDTA may have broad-spectrum antimicrobial activity, may have optimal anticoagulant activity, and may be highly efficacious in preventing catheter colonization.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Bacteremia; Catheterization, Central Venous; Drug Therapy, Combination; Edetic Acid; Enterobacter; Enterobacteriaceae Infections; Fatal Outcome; Female; Humans; Male; Middle Aged; Minocycline; Recurrence; Staphylococcal Infections

Topics: Actinomycetales Infections; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Gentamicins; Humans; Immunocompromised Host; Lung Transplantation; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Rhodococcus equi; Teicoplanin

A 55-year-old man was admitted to our department one month after resection of rectal carcinoma, with complaints of fever and general malaise. Shock developed rapidly after admission. The chest X-ray film and computed tomography showed diffuse small nodular shadows and bilateral pleural effusion. Septic lung caused by Methicillin-resistant Staphylococcus epidermidis (MRSE) was diagnosed from the results of a bacteriological study. This bacteria is a Coagulase Negative Staphylococcus (CNS). Chemotherapy with Minocycline and Cefotiam was effective. Characteristic radiologic features of this case may be related to the early stage of adult respiratory distress syndrome (ARDS) and septic pulmonary microembolism.

Topics: Anti-Bacterial Agents; Bacteremia; Cefotiam; Cephalosporins; Humans; Lung Diseases; Male; Methicillin Resistance; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus epidermidis

A sixteen year old female was feverish from June 12, 1993. Methicillin-resistant Staphylococcus aureus was isolated from the blood, the diagnosis of MRSA sepsis was established. Vancomycin (2 g/day) was administered for eighteen days, but MRSA was not eradicated in the blood culture. Then she was administered a combination therapy of arbekacin (200 mg/day) and imipenem/cilastain (1 g/day) for seven days, but MRSA in the blood was cultured continuously. The sequential combination therapy of netilmycin (200 mg/day) and minocycline (200 mg/day) was started, MRSA was eradicated from the blood culture after four days. The sequential combination therapy netilmycin and minocycline was seemed to be effective for MRSA infection.

Topics: Adolescent; Bacteremia; Drug Therapy, Combination; Female; Humans; Methicillin Resistance; Minocycline; Netilmicin; Staphylococcal Infections; Staphylococcus aureus

Local drug delivery by using biocompatible polymers has been developed in the treatment of periodontitis for many years. The purpose of this study was to examine the release kinetics of minocycline from monolithic film prepared from polycaprolactone and polyethylene glycol and to examine the antimicrobial activity in vitro. Polycaprolactone (Mwt 60,000), polyethylene glycol and minocyline was dissolved by chloroform, which was vigorously stirred for 24 hours and it was dried in vacuum chamber. The thickness of cast films containing 20%, 30% and 40% minocycline was 200 +/- 10 microns. Release rate of minocycline from the film was measured by means of a UV spectrophotometer. In vitro releasing test, each film showed a large burst effect within first two and three hours and a steady state release kinetic at the rate of 4-8 micrograms/cm/hour for 7 days. In antimicrobial test, each sample (one fourth inch in diameter) sunk in the broth that had been innoculated with periodontopathic bacteria showed growth inhibitory activity after 48 hr anaerobic incubation. In cytotoxicity test, there was no significant cytotoxic effect in casting film to human gingival fibroblast. This study showed that, by embedding minocycline in polycaprolactone, it is feasible to obtain substained release of the drug within the periodontal pocket for seven days and should be useful tool for elimination of pathogenic microflora from periodontal pocket or reducing inflammation in periodontal disease.

Topics: Adolescent; Adult; Bacteremia; Drug Delivery Systems; Female; Humans; Male; Minocycline; Periodontal Pocket; Polyesters; Polyethylene Glycols