minocycline and Sepsis

Several studies have investigated the safety and efficacy of antimicrobial peripherally inserted central catheters (PICCs), and the results are conflicting. Therefore, in this systematic review and meta-analysis, we aimed to summarize and identify the effect of antimicrobial PICCs on central line-associated bloodstream infection (CLABSI) risk.. A systematic search of PubMed, Ovid MEDLINE, Ovid Embase, and Web of Science was performed to identify relevant studies up to December 2022.. A total of 9 studies were included for analysis. There were 7 retrospective/prospective cohort studies and 2 randomized controlled trials. The 9 studies involved 51,373 patients with PICCs. Among these patients, 6,563 (12.8%) antimicrobial-coated/impregnated PICCs and 44,810 (87.2%) nonantimicrobial-impregnated PICCs were inserted. The meta-analysis showed that antimicrobial PICCs had a nonsignificant association with lower CLABSI risk compared with noncoated PICCs (relative risk [RR] = 0.67; 95% CI, 0.43-1.05). In the subgroup analysis, minocycline-rifampin-(RR = 0.30; 95% CI, 0.19-0.49) or chlorhexidine-coated (RR = 0.61; 95% CI, 0.04-8.55) PICCs showed an association with reduced risk of CLABSI. In the adult population, antimicrobial PICCs had a nonsignificant association with lower CLABSI risk (RR = 0.50; 95% CI, 0.20-1.22).. This systematic review and meta-analysis suggested that antimicrobial PICCs had a nonsignificant association with lower CLABSI risk compared with noncoated PICCs. Minocycline-rifampin-or chlorhexidine-coated PICCs showed an association with reduced risk of CLABSI.

Topics: Adult; Anti-Infective Agents; Catheter-Related Infections; Catheterization, Central Venous; Catheters; Central Venous Catheters; Chlorhexidine; Humans; Minocycline; Prospective Studies; Retrospective Studies; Rifampin; Risk Factors; Sepsis

Carbapenem-resistant Enterobacteriaceae are a group of virulent, drug-resistant gram-negative bacteria that are increasingly the cause of infection. Such infections are associated with a high morbidity and mortality and increased health care costs. Management of these infections requires recognition of patients at risk for multidrug-resistant microbial colonization and infections, identification of the causative organism, and rapid, appropriate treatment. Lack of awareness of proper isolation of patients harboring these organisms and delay in prescribing antibiotics such as tigecycline and polymyxins contribute to the spread of infection in intensive care units. Surveillance and infection control measures are paramount in preventing outbreaks of infection caused by carbapenem-resistant Enterobacteriaceae. Critical care nurses are in a vital position to monitor patients at risk for such infections and to promote infection prevention measures.

Topics: Anti-Bacterial Agents; Carbapenems; Critical Care Nursing; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Humans; Infection Control; Intensive Care Units; Minocycline; Sepsis; Tigecycline

Therapeutic strategies in the management of skin and soft tissue infections should take account of different variables: epidemiological trends (community or hospital acquired infections), pathogen or pathogens involved, virulence, seriousness of pathology (possible co-morbidities, knowledge of local epidemiology and antimicrobial susceptibility patterns of community and hospital strains. Therapy often should be started promptly, and on an empiric base, once microbiological analysis have been performed, waiting for culture and antimicrobial susceptibility testing. Surgical incision and drainage represent essential therapeutic procedures in the treatment of many complicated skin and soft tissue infections such as abscesses and fasciitis. Gram-positive bacteria and specifically Staphylococcus aureus, are the main cause of such kind of infections. Therefore antistaphylococcal beta-lactams represents a first choice in empirical antimicrobial chemotherapy. Considering high incidence of MRSA in Italian hospitals, treatment of hospital acquired skin and soft tissue infections should be based on glycopeptides combined with third generation cephalosporins, piperacillin-tazobactam, carbapenems or fluoroquinolones. Recently, new drugs (as linezolid, daptomycin, tigecycline) demonstrated good efficacy in the treatment of serious infections caused by multi-drug resistant microorganisms. Most recent guidelines for the diagnosis and treatment of skin and soft tissue infections were published in 2005 by Infectious Diseases Society of America (IDSA). In Italy, the multidisciplinary group of Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) published guidelines for the treatment of skin and soft tissue infections in Internal Medicine wards in 2005. General approach and methodology in writing test were based on analysis of data from available scientific literature and comparing them with actual Italian epidemiological trends and drug prescribing policy. Considering these guidelines, we updated the newest antimicrobial drugs suggested for the treatment of skin and soft tissue infections, such as daptomycin and tigecycline.

Topics: Acetamides; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Cross Infection; Daptomycin; Debridement; Drainage; Drug Therapy, Combination; Humans; Italy; Linezolid; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Sepsis; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Wound Infection

Bloodstream infection related to a central venous catheter is a substantial clinical and economic problem. To develop policy for managing the risks of these infections, all available evidence for prevention strategies should be synthesized and understood.. We evaluate evidence (1985-2006) for short-term antimicrobial-coated central venous catheters in lowering rates of catheter-related bloodstream infection (CRBSI) in the adult intensive care unit. Evidence was appraised for inclusion against predefined criteria. Data extraction was by 2 independent reviewers. Thirty-four studies were included in the review. Antiseptic, antibiotic, and heparin-coated catheters were compared with uncoated catheters and one another. Metaanalysis was used to generate summary relative risks for CRBSI and catheter colonization by antimicrobial coating.. Externally impregnated chlorhexidine/silver sulfadiazine catheters reduce risk of CRBSI relative to uncoated catheters (RR, 0.66; 95% CI: 0.47-0.93). Minocycline and rifampicin-coated catheters are significantly more effective relative to CHG/SSD catheters (RR, 0.12; 95% CI: 0.02-0.67). The new generation chlorhexidine/silver sulfadiazine catheters and silver, platinum, and carbon-coated catheters showed nonsignificant reductions in risk of CRBSI compared with uncoated catheters.. Two decades of evidence describe the effectiveness of antimicrobial catheters in preventing CRBSI and provide useful information about which catheters are most effective. Questions surrounding their routine use will require supplementation of this trial evidence with information from more diverse sources.

Topics: Anti-Bacterial Agents; Carbon; Catheterization; Catheterization, Central Venous; Chlorhexidine; Cross Infection; Humans; Intensive Care Units; Minocycline; Platinum; Rifampin; Sepsis; Silver

The pharmacodynamic and pharmacokinetic characteristics of antimicrobial agents are the two fundamental pharmacological components which provide a rationale for the choice of therapy for intraabdominal infections, and especially serious infections. The most important PK-PD parameters are well known which can potentiate therapeutic efficacy. Antimicrobial agents can be subdivided into categories based on whether their activity is dependent on concentration or exposure time. Therefore, a correct dosing regimen for the time-dependent molecules (i.e. beta-lactams, linezolid, tigecycline) should prolong the maximum exposure time to maintain serum levels over the minimum inhibitory concentration (MIC). The concentration-dependent molecules, on the other hand, which include aminoglycosides and fluoroquinolones, should be given in order to reach maximum concentrations, since they are bactericidal in direct proportion to their concentrations and possess a prolonged post-antibiotic effect.

Topics: Abdominal Abscess; Acetamides; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactams; Digestive System Diseases; Drug Therapy, Combination; Fluoroquinolones; Humans; Linezolid; Metronidazole; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Peritonitis; Sepsis; Tigecycline; Treatment Outcome; Virginiamycin

Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Breast Neoplasms; Ciprofloxacin; Drug Resistance, Microbial; Female; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Transplantation; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Pneumonia, Bacterial; Rifampin; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores > 15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum β-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Drug Therapy, Combination; Enterococcus; Escherichia coli; Female; Germany; Humans; Intensive Care Units; Intraabdominal Infections; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Multiple Organ Failure; Prospective Studies; Sepsis; Severity of Illness Index; Skin Diseases, Bacterial; Staphylococcus aureus; Tigecycline; Treatment Outcome; Young Adult

We previously demonstrated that minocycline-EDTA was efficacious at preventing catheter-related bloodstream infections (BSIs) in three patients with recurrent infections. This study compared heparin with minocycline-EDTA as flush solutions used among dialysis patients with central venous catheters, a high-risk group for catheter-related BSI.. Patients were enrolled within 72 hours of catheter insertion and randomized to receive heparin or minocycline-EDTA as a flush after each dialysis session. Each syringe containing flush solution was wrapped in orange plastic to conceal the type of solution it contained. Patients were observed for evidence of infection and catheter thrombosis. After catheters were removed, cultures were performed to determine whether microbial colonization had occurred.. During a 14-month period, 60 patients were enrolled (30 in each group). The two groups had similar demographics and underlying diseases. Catheter survival at 90 days was 83% for the minocycline-EDTA group versus 66% for the heparin group (P = .07). Significant catheter colonization, a surrogate measure of catheter-related infection, was significantly more frequent in the heparin group (9 of 14 vs 1 of 11; P = .005). There was only one catheter-related bacteremia and it occurred in the heparin group.. When compared with heparin, minocycline-EDTA had a better 90-day catheter survival (P = .07) and a decreased rate of catheter colonization. This pilot study warrants a larger prospective, randomized trial.

Topics: Anti-Bacterial Agents; Anticoagulants; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Double-Blind Method; Drug Combinations; Edetic Acid; Equipment Contamination; Female; Heparin; Humans; Infection Control; Male; Middle Aged; Minocycline; North Carolina; Pilot Projects; Prospective Studies; Renal Dialysis; Risk Factors; Sepsis; Survival Analysis; Therapeutic Irrigation; Thrombosis; Time Factors

We sought to compare the impact of antimicrobial impregnation to that of tunneling of long-term central venous catheters on the rates of catheter colonization and catheter-related bloodstream infection.. Tunneling of catheters constitutes a standard of care for preventing infections associated with long-term vascular access. Although antimicrobial coating of short-term central venous catheters has been demonstrated to protect against catheter-related bloodstream infection, the applicability of this preventive approach to long-term vascular access has not been established.. A prospective, randomized clinical trial in 7 university-affiliated hospitals of adult patients who required a vascular access for > or = 2 weeks. Patients were randomized to receive a silicone central venous catheter that was either impregnated with minocycline and rifampin or tunneled. The occurrence of catheter colonization and catheter-related bloodstream infection was determined.. Of a total of 351 inserted catheters, 346 (186 antimicrobial-impregnated and 160 tunneled) were analyzed for catheter-related bloodstream infection. Clinical characteristics were comparable in the 2 study groups, but the antimicrobial-impregnated catheters remained in place for a shorter period of time (mean, 30.2 versus 43.8 days). Antimicrobial-impregnated catheters were as likely to be colonized as tunneled catheters (7.9 versus 6.3 per 1000 catheter-days). Bloodstream infection was 4 times less likely to originate from antimicrobial-impregnated than from tunneled catheters (0.36 versus 1.43 per 1000 catheter-days).. Antimicrobial impregnation of long-term central venous catheters may help obviate the need for tunneling of catheters.

Topics: Anti-Bacterial Agents; Catheterization, Central Venous; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Rifampin; Sepsis; Silicones

Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control.. To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections.. Multicenter, randomized clinical trial.. Five university-based medical centers.. 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters.. 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin. Untreated, uncoated catheters (n = 151) were used as controls.. Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections.. The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001). Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01). Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05). No adverse effects related to the coated catheters or antimicrobial resistance were seen. An estimate showed that the use of coated catheters could save costs.. Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections. The use of these catheters may save costs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Catheterization, Central Venous; Catheters, Indwelling; Cost-Benefit Analysis; DNA, Bacterial; DNA, Viral; Double-Blind Method; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Male; Middle Aged; Minocycline; Rifampin; Risk; Sepsis; Treatment Outcome

Twenty-eight patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were clinically studied for the effectiveness of the time-difference combination use of netilmicin (NTL) and minocycline (MINO). The patients were treated with NTL 100 mg and two hours later, with MINO 100 mg intravenously, twice daily, in the morning and evening for 14 days. Of 26 patients, MRSA was eradicated in 16 (61.5%), decreased in one, and unchanged in nine. Superinfections occurred with Serratia marcescens and Pseudomonas aeruginosa in two patients. The clinical efficacies were assessed in two patients with septicemia, 16 with pneumonia, and eight with chronic bronchitis. The obtained results were excellent in four patients, good in 15, fair in six, and poor in one patient. The rate of effectiveness was 73.1% (19/26). The overall clinical effectiveness judged by the committee was good in 19, fair in five, and poor in two patients. The efficacy rate was also 73.1% (19/26). Coagulase type II of MRSA was found in 23 patients, and coagulase type III in three patients, with overall clinical efficacy rates of 73.9% (17/23) and 66.7% (2/3), respectively. A side effect of eruption was observed in one patient, and its incidence was 3.6% (1/28). Abnormal laboratory test results were observed in 16 patients (57.1%), including abnormal liver function in 14 patients, abnormal kidney function in three, and increased eosinophils in three. Laboratory abnormalities occurred twelve of 16 bedridden patients, and this rate was higher than that in non bedridden patients. However, these abnormalities were all mild, transient, and immediately recovered after the treatment. In conclusion, the time-difference combination therapy using NTL and MINO was effective in the treatment of MRSA infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bronchitis; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Japan; Male; Methicillin Resistance; Middle Aged; Minocycline; Netilmicin; Pneumonia, Staphylococcal; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Superinfection

Sepsis is associated with several comorbidities in survivors, such as posttraumatic stress disorder (PTSD). This study investigated whether rats that survive sepsis develop the generalization of fear memory as a model of PTSD. Responses to interventions that target the endothelin-1 (ET-1)/cannabinoid system and glial activation in the initial stages of sepsis were evaluated. As a control, we evaluated hyperalgesia before fear conditioning. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. CLP-induced sepsis with one or three punctures resulted in fear generalization in the survivors 13 and 20 days after the CLP procedure, a process that was not associated with hyperalgesia. Septic animals were intracerebroventricularly treated with vehicle, the endothelin receptor A (ET

Topics: Animals; Cannabinoids; Hyperalgesia; Minocycline; Neuroinflammatory Diseases; Rats; Rats, Wistar; Receptors, Cannabinoid; Sepsis; Stress Disorders, Post-Traumatic

The aim of the study was to explore the mechanism by which minocycline protects the blood-brain barrier (BBB) in septic rats.. A sepsis rat model was generated in healthy, male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were randomly divided into four groups and treated as follows: sham-operated plus normal saline (Sham + S group), CLP plus normal saline (CLP + S group), CLP plus minocycline pretreatment (CLP + M1 group), and CLP plus minocycline treatment (CLP + M2 group). Rats in the CLP + M1 group received 45 mg/kg minocycline by intraperitoneal injection every 12 h for 72 h. Rats in the Sham + S and CLP + S groups were injected with the same volume of normal saline every 12 h for 72 h. Rats in the CLP + M2 group were intraperitoneally injected with 45 mg/kg minocycline immediately after CLP and once every 12 h for 72 h. All rats were sacrificed at 72 h after operation. Tumor necrosis factor α and interleukin 6 levels, the expression of ionized calcium-binding adaptor molecule-1 (Iba-1), and the permeability of the BBB were measured. The expression of matrix metalloproteinases-9 (MMP-9) and the tight junction proteins zonula occludens-1 (ZO-1) and occludin was detected by Western blot. In addition, Evans blue (EB) staining, immunohistochemistry, and ELISA analysis were carried out.. Minocycline pretreatment significantly inhibited microglial activation, decreased the sepsis-induced expression of MMP-9, increased the expression of ZO-1 and occludin, and improved the permeability of the BBB. Minocycline treatment failed to inhibit microglial activation, decrease the sepsis-induced expression of MMP-9, increase the expression of ZO-1 or occluding, or improve the permeability of the BBB.. Minocycline pretreatment can effectively improve the altered permeability of the BBB caused by sepsis. The mechanism may be related to the inhibition of microglial activation and MMP-9 expression and increased expression of ZO-1 and occludin.

Topics: Animals; Blood-Brain Barrier; Male; Matrix Metalloproteinase 9; Minocycline; Occludin; Rats; Rats, Sprague-Dawley; Saline Solution; Sepsis

This experiment was carried out to provide a basis for the treatment of clinical bloodstream infections by analyzing the drug resistance characteristics and integrated gene distribution of Escherichia coli in bloodstream infections in elderly patients. For this aim, E. coli were collected for bacterial identification and drug sensitivity testing from bloodstream infections in elderly patients in the hospital from January 2016 to December 2019. ESBLs positive strains were assayed for genotypes and their integron carriage rates by PCR amplification. The characteristics and differences of various genotype rates were compared and analyzed. Results showed that a total of 230 E. coli strains were isolated. The detection rate of ESBLs-producing bacteria was 37.39 %. ESBLs-producing E. coli showed a high rate of resistance to cefepime, levofloxacin, cotrimoxazole, and ticarcillin/clavulanic acid (>40%). The resistance rate of 230 strains of E. coli to meropenem, minocycline, amikacin, gentamicin and cefoxitin was less than 20%. Among the ESBLs-producing E. coli in bloodstream infections in elderly patients, CTX-M-9 accounted for 27.91%, CTX-M-2 for 17.44%, and SHV for 13.95%. The detection rate of type I integrated genes was 41.30%, and type II and III integrated genes were not detected. ESBLs-producing genotyping-positive bacteria were detected with more than 50% of type I integrated genes. It was concluded that type I integrated genes in ESBLs-producing E. coli isolated from elderly patients carried resistance genes such as CTX-M-9 and CTX-M-2 aggravating multi-drug resistance in bacteria.

Topics: Aged; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefoxitin; Clavulanic Acid; Drug Resistance; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Integrons; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Sepsis; Ticarcillin; Trimethoprim, Sulfamethoxazole Drug Combination

Oxidative stress and inflammatory responses play an important role in acute lung injury (ALI). Although minocycline (MINO) has anti-inflammatory effects and is a promising candidate in treating inflammatory diseases, the effect of MINO on ALI during sepsis is still unclear.. In the present study, a mouse model with intestinal perforation was established. C57BL/6 mice received cecal ligation and puncture (CLP) to induce sepsis-associated ALI. MINO was used to treat the mice via intraperitoneal injection at different doses (negative control, 20 mg/kg, 50 mg/kg and 100 mg/kg, respectively) 24 h after CLP. The severity of lung injury was evaluated by pathological examination, and lung wet / dry weight ratio was calculated to evaluate the severity of pulmonary edema. The changes of TNF-α, IL-1β, IL-6, PGE2, MDA, NF-κB, Nrf2, Keap1 and lncRNA MALAT1 levels in lung tissues of the mice were detected with ELISA, chemical colorimetry, Western blot or qRT-PCR.. MINO ameliorated the lung edema and lung injury of the mice induced by CLP in a dose-dependent manner. MINO administration could significantly down-regulate expressions of TNF-α, IL-6, IL-1β, PGE2 and MDA in lung tissues of the mice. Mechanistically, MINO exerted the effects of anti-inflammation and anti-oxidative stress through down-regulating the expression of MALAT1 and regulating Nrf2/Keap1 and NF-κB signaling pathways.. MINO represses oxidative stress and inflammatory response during sepsis-induced ALI via down-regulating MALAT1 expression, and it has the potential to treat septic ALI.

Topics: Acute Lung Injury; Animals; Dinoprostone; Interleukins; Kelch-Like ECH-Associated Protein 1; Lung; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Minocycline; NF-E2-Related Factor 2; Oxidative Stress; RNA, Long Noncoding; Sepsis; Tumor Necrosis Factor-alpha

Sepsis promotes an inflammatory state in the central nervous system (CNS) that may cause autonomic, cognitive, and endocrine changes. Microglia, a resident immune cell of the CNS, is activated in several brain regions during sepsis, suggesting its participation in the central alterations observed in this disease. In this study, we aimed to investigate the role of microglial activation in the neuroendocrine system functions during systemic inflammation. Wistar rats received an intracerebroventricular injection of the microglial activation inhibitor minocycline (100 μg/animal), shortly before sepsis induction by cecal ligation and puncture. At 6 and 24 h after surgery, hormonal parameters, central and peripheral inflammation, and markers of apoptosis and synaptic function in the hypothalamus were analyzed. The administration of minocycline decreased the production of inflammatory mediators and the expression of cell death markers, especially in the late phase of sepsis (24 h). With respect to the endocrine parameters, microglial inhibition caused a decrease in oxytocin and an increase in corticosterone and vasopressin plasma levels in the early phase of sepsis (6 h), while in the late phase, we observed decreased oxytocin and increased ACTH and corticosterone levels compared to septic animals that did not receive minocycline. Prolactin levels were not affected by minocycline administration. The results indicate that microglial activation differentially modulates the secretion of several hormones and that this process is associated with inflammatory mediators produced both centrally and peripherally.

Topics: Animals; Brain; Corticosterone; Disease Models, Animal; Male; Microglia; Minocycline; Neurons; Neurosecretory Systems; Oxytocin; Rats; Rats, Wistar; Sepsis; Vasopressins

Myocardial damage is responsible for the high mortality of sepsis. However, the underlying mechanism is not well understood. Cardiomyocyte autophagy alleviates the cardiac injury caused by myocardial infarction. Enhanced cardiomyocyte autophagy also has protective effects against cardiomyocyte mitochondrial injury. Minocycline enhances autophagy in many types of cells under different types of pathological stress and can be easily taken up by cardiomyocytes. The present study investigated whether minocycline prevented myocardial injury caused by sepsis and whether cardiomyocyte autophagy participated in this process. The results indicated that minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved myocardial mitochondrial and cardiac function. Minocycline upregulated protein kinase B (Akt) phosphorylation, inhibited mTORC1 expression and enhanced mTORC2 expression. In conclusion, minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved cardiac function. The underlying mechanisms were associated with mTORC1 inhibition and mTORC2 activation. Thus, our findings suggest that minocycline may represent a potential approach for treating myocardial injury and provide novel insights into the underlying mechanisms of myocardial injury and dysfunction after sepsis.

Topics: Animals; Autophagy; Male; Mice; Mice, Inbred C57BL; Minocycline; Mitochondria; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Phosphorylation; Proto-Oncogene Proteins c-akt; Sepsis; Signal Transduction; TOR Serine-Threonine Kinases; Up-Regulation

The mortality rate associated with

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Ciprofloxacin; Colony Count, Microbial; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Survival Analysis; Tigecycline; Vibrio Infections; Vibrio vulnificus

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

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Cross Infection; Female; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Prospective Studies; Recurrence; Risk Factors; Sepsis; Thienamycins; Tigecycline; Time Factors

Tigecycline is the first member of the glycylcycline family. There are rarely reports of tigecycline causing coagulopathy and hypofibrinogenemia until now. We report a case on tigecycline-associated coagulopathy and hypofibrinogenemia and discuss the characteristics of the adverse reaction.. A 47-year-old male patient with severe acute cholangitis who developed sepsis was treated with a high dosage (100 mg twice daily) of tigecycline. He experienced coagulopathy and hypofibrinogenemia as substantiated by increased levels of prolonged prothrombin time (PT), the international normalized ratio (INR) and activated partial thromboplastin time (APTT), and in particular, the fibrinogen (FIB) levels obviously decreased.. Coagulopathy and hypofibrinogenemia.. We discontinued tigecycline and gave the patient several blood products to prevent spontaneous bleeding.. The adverse reaction disappeared after the withdrawal of tigecycline. After 30 days of hospitalization, the patient discharged with symptom free.. We suggest that coagulation parameters should be closely monitored in patients treated with tigecycline, specifically in patients who may be renal insufficiency, female or use the high-dose.

Topics: Afibrinogenemia; Anti-Bacterial Agents; Blood Coagulation Disorders; Cholangitis; Humans; Male; Middle Aged; Minocycline; Sepsis; Tigecycline

Tigecycline is a broad spectrum antimicrobial agent, structurally similar to minocycline and that shares some tetracycline-related side effects. A case report is presented on a 68-year-old female who received tigecycline for a sepsis of unknown origin and who, in the following 5days, developed abdominal pain and elevated pancreatic enzymes, which suggested acute pancreatitis. After ruling out other origins, and according to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of the acute pancreatitis, a complication that has been reported 5 times in the database of the Spanish pharmacosurveillance system since 2009. Close monitoring of abdominal signs and symptoms is recommended during treatment with tigecycline, since adverse effects affecting the digestive system are the most prevalent ones when using this drug.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Critical Care; Drug Substitution; Fatal Outcome; Female; Humans; Minocycline; Multiple Organ Failure; Pancreatitis; Sepsis; Tigecycline

Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. We divided mice into four groups; sham + vehicle, sham + MINO (60 mg/kg, i.p. for 3 consecutive days before slice preparation), CLP + vehicle, and CLP + MINO. We tested LTP in the CA1 region of the hippocampus, using slices taken 24 h after surgery. Because MINO is also anti-inflammatory, LTP was analyzed following 30 min of IL-1 receptor antagonist (IL-1ra) perfusion. The endotoxin level in the blood was increased at 24 h after CLP operations regardless of MINO administrations, and LTP in the CLP + vehicle group mice was severely impaired (P < 0.05). High doses of MINO prevented the LTP impairment during sepsis in the CLP + MINO group. Interleukin (IL)-1ra administration ameliorated LTP impairment only in the CLP + vehicle group (P < 0.05); it had no additional effects on LTP in the CLP + MINO group. In conclusion, we have provided the first evidence that MINO prevents impaired LTP related to sepsis-induced encephalopathy in the mouse hippocampus, and that mechanisms associated with IL-1 receptor activity may be involved.

Topics: Animals; Brain Diseases; Hippocampus; Long-Term Potentiation; Male; Mice; Minocycline; Sepsis

The use of peripherally inserted central catheters (PICCs) has increased over the past few years due to their less serious insertion complications. The purpose of the present study was to determine whether patients receiving PICCs impregnated with minocycline and rifampin had a lower rate of CLABSI compared with a concurrent control group of patients receiving uncoated PICCs.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Catheter-Related Infections; Catheterization, Central Venous; Catheters; Female; Humans; Male; Middle Aged; Minocycline; Prevalence; Rifampin; Risk Assessment; Sepsis; Young Adult

Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 μg/ml versus 3 μg/ml [P < 0.05] and 2 μg/ml versus 3.4 μg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Colistin; Enzyme-Linked Immunosorbent Assay; Imipenem; Interleukin-10; Lysophosphatidylcholines; Mice; Microbial Sensitivity Tests; Minocycline; Pneumonia; Sepsis; Tigecycline; Tumor Necrosis Factor-alpha

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Colectomy; Enterocolitis, Pseudomembranous; Female; Humans; Intraabdominal Infections; Male; Metronidazole; Middle Aged; Minocycline; Recurrence; Retrospective Studies; Sepsis; Tigecycline; Treatment Outcome; Vancomycin

MRSA is the predominant pathogen responsible for fatal burn wound infection in patients. Antibiotic resistance and its ability to form biofilms on the surface of burn wounds limit the use of antibiotics to contain this pathogen. The results of present study have shown that single dose of combination therapy of endolysin MR-10 (50μg/s.c) and minocycline (50mg/kg/orally) resulted in 100% survival of group of mice with systemic MRSA infection. Maximum reduction in bacterial load in various organs was observed in the group that received combination therapy. In comparison to control, a significant reduction (p<0.01) of 4.82, 1.81, 1.51, 1.2 logs was observed in skin, blood, liver and spleen respectively, by 3rd day post infection. As a result of which, all organs became sterile thereby protecting mice from mortality. Histopathological analysis corroborated our findings showing no signs of inflammation and bacterial infection in the group that received combination therapy. Treatment of localized burn wound infection with combination therapy resulted in early resolution of infection followed by fast healing. The group that received combination therapy showed complete resolution of infection in less than 10days. Moreover, the skin samples obtained from animals treated with combination therapy showed no myeloperoxidase (MPO) activity on 10th day post treatment. In combination therapy group, ∼98% wound contraction was observed by 12th day followed by complete closure of wound within ∼14days. The histopathological analysis showed no signs of inflammation and infection. Collagen staining revealed early signs of re-epithelization of epidermis and signs of collagen regeneration in-group that received combination therapy. Hence, this study suggests that the combined therapy of endolysin MR-10 and minocycline is a better option in controlling burn wound infections.

Topics: Administration, Oral; Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; Burns; Disease Models, Animal; Drug Therapy, Combination; Endopeptidases; Female; Histocytochemistry; Injections, Subcutaneous; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Minocycline; Sepsis; Staphylococcal Infections; Survival Analysis; Time Factors; Treatment Outcome; Wound Infection

Acinetobacter baumannii is the most common species to have developed resistance to antibiotics. Due to increasing levels of drug resistance, the available therapeutic options are insufficient in A. baumannii infections. This study investigated the efficacy of doripenem monotherapy versus doripenem combination therapy with sulbactam, amikacin, colistin and tigecycline in experimental sepsis. A carbapenem-resistant A. baumannii was used to develop a sepsis model in 8-10-week-old Balb/c mice by intraperitoneal injection. Antibiotic therapies were initiated two hours after injection of bacterial suspension. Necropsy was performed at 24, 48 and 72 hours and cultures were made from heart, lung, liver and spleen samples. Bacterial loads of lung and liver were calculated as CFU/g. Combination therapies with doripenem were more effective than monotherapy at 24 and 48 hours of infection but no differences between groups were detected at 72 hours. The combination of doripenem with tigecycline and amikacin began to eradicate the bacterial load of lung and liver after 48 hours of infection, whereas doripenem+sulbactam and doripenem+colistin were started to eradication at 72 hours. The results of the study showed that combination therapies with doripenem are more effective than monotherapy and the combination of doripenem with tigeycline or amikacin has more rapid bactericidal effect than that with sulbactam or colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Male; Mice; Mice, Inbred BALB C; Minocycline; Sepsis; Sulbactam; Tigecycline

This study compared the effect of monotherapy of colistin, tigecycline, and their combination in sepsis model of mice. OXA-48 producing Carbapenem-resistant Klebsiella pneumoniae (CRKP) strain was used in Balb/c mice. The mice were divided into competent and Methylprednisolone acetate (MPA)-treated groups. Each group was sub-divided into (1) colistin or (2) tigecycline monotherapy and (3) colistin/tigecycline combination therapy. After 3 hours of intraperitoneal bacterial inoculation, antimicrobials were administered, and mice were sacrificed at 24 and 48 hours Time-kill curve study demonstrated that colistin sulphate had early bactericidal activity following re-growth. In competent and MPA-treated groups of mice at 24 hours, bacterial counts in liver samples significantly lowered compared to control, however, there were no statistically differences between monotherapy and combination therapy subgroup. Bacterial count in lung samples of competent group was significantly lesser than control for all three antimicrobial subgroups at 24 hours Colistin plus tigecycline combination therapy was not superior against colistin or tigecycline monotherapy.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Klebsiella pneumoniae; Methylprednisolone; Methylprednisolone Acetate; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Structure-Activity Relationship; Tigecycline

The development of sepsis in patients with traumatic brain injury increases mortality, exacerbates morphological and functional cerebral damage, and causes persistent neuroinflammation, including microglial activation. The administration of antibiotics possessing both antimicrobial and immunomodulatory activity might attenuate both sepsis and posttraumatic cerebral inflammation. We compared the potential therapeutic efficacy of two tetracyclines, minocycline and the newer generation tigecycline, on functional neurobehavioral impairment and regional histopathological damage in an experimental model of combined traumatic brain injury and sepsis.. Prospective, experimental animal study.. University Research Laboratory.. Adult male Sprague-Dawley rats.. Controlled cortical impact was used to induce traumatic brain injury and cecal ligation and puncture for sepsis. Immediately following injury, animals were treated with minocycline (45 mg/kg intraperitoneal), tigecycline (7.5 mg/kg intraperitoneal), or saline every 12 hours for 3 days.. The development of sepsis and cerebral inflammatory response were evaluated, respectively, by 1) growth of peritoneal microorganisms and clinical variables and 2) tumor necrosis factor-α expression in the perilesional cortex. To assess posttraumatic outcome, vestibulomotor and cognitive function were evaluated at different time points for 14 days post injury whereupon animals were killed and cerebral tissue analyzed for lesion volume, regional hippocampal (CA1/CA3) cell death, and microglial activation in the perilesional cortex, lesion core zone, and choroid plexus. Treatment with both antibiotics reduced microorganism growth, body weight loss, and mortality but had no effect on vestibulomotor or cognitive function. Minocycline alone attenuated postinjury cortical lesion volume, hippocampal CA3 neuronal cell loss, tumor necrosis factor-α expression, and the extent of microglial activation and infiltration.. The significantly heightened mortality caused by the superimposition of sepsis upon traumatic brain injury can be reduced by administration of both antibiotics but only minocycline can decrease the extent of cell death in selectively cortical and hippocampal brain regions, via, in part, a reduction in cerebral inflammation.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Brain Injuries; Encephalitis; Immunologic Factors; Male; Minocycline; Neuroprotective Agents; Prospective Studies; Rats; Rats, Sprague-Dawley; Sepsis; Tigecycline

Topics: Animals; Anti-Inflammatory Agents; Brain Injuries; Encephalitis; Male; Minocycline; Neuroprotective Agents; Sepsis; Tigecycline

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

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

In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice.. Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points.. Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone.. These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Sulbactam; Tigecycline; Time Factors

To investigate the trend of tigecycline susceptibility and mechanisms behind tigecycline non-susceptibility in Klebsiella pneumoniae and Escherichia coli isolates causing neonatal septicaemia (2007-10).. MICs of tigecycline for the isolates were determined. The isolates were evaluated for β-lactamases and carbapenemases. Molecular typing of the tigecycline-resistant isolates was performed. Expression of efflux pump genes (acrA, acrB and tolC) and regulators (soxS and ramA) was examined by real-time RT-PCR and western blotting. Sequencing of the ramA and ramR genes was carried out to identify mutations within these genes.. Tigecycline susceptibility was evaluated in all K. pneumoniae (n = 57) and E. coli (n = 19) blood isolates. The prevalence of extended-spectrum β-lactamase (ESBL)-producing organisms was high, but tigecycline non-susceptibility remained low in these isolates. Though MIC values of tigecycline remained in the susceptible range, there was a 2-fold increase in the value of MIC90 from 2007 to 2010. Over the 4 year period K. pneumoniae showed higher MIC values of tigecycline in comparison with E. coli. Tigecycline non-susceptibility was not observed among carbapenem-resistant isolates. Only two ESBL-producing clonally distinct K. pneumoniae isolates showed tigecycline resistance with overexpression of ramA and the AcrAB-TolC pump. No mutations were present within the ramA and ramR genes that might enhance the expression of the pump.. The study showed for the first time the trend of tigecycline susceptibility in E. coli and K. pneumoniae causing neonatal septicaemia. Tigecycline still has potent antimicrobial effects against most ESBL- or carbapenemase-producing K. pneumoniae and E. coli, but the increasing MIC values make it essential to be vigilant.

Topics: Anti-Bacterial Agents; beta-Lactamases; Blotting, Western; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Gene Expression Profiling; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Molecular Typing; Mutant Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sepsis; Sequence Analysis, DNA; Tigecycline

To discuss pharmacotherapy challenges encountered during treatment of a pediatric oncology patient with Burkholderia cepacia septicemia.. An 11-year-old male with a history of aplastic anemia presented to the emergency department with a 1-day history of cough and purulent nasal discharge 6 months after undergoing bone marrow transplant. Blood cultures obtained from the patient's Broviac catheter revealed gram-negative rods. Piperacillin/tazobactam and tobramycin were administered, but the patient worsened clinically, with fever and chills. B. cepacia was identified as the offending pathogen, and the therapy was changed to meropenem and ciprofloxacin, as piperacillin/ tazobactam and tobramycin are ineffective against Burkholderia spp. Intravenous trimethoprim/sulfamethoxazole, the drug of choice for Burkholderia spp. infections, was unavailable as it had been placed on national manufacturer backorder. The patient improved initially, but he later experienced recurrence of fever, and blood culture results were positive for Burkholderia spp. Infection was eradicated after removal of the central line and administration of ceftazidime and oral minocycline.. Literature reveals few cases of B. cepacia in pediatric oncology patients, and to our knowledge, no cases have been reported in bone marrow transplant patients in the US. Burkholderia spp. is highly resistant to many antibiotics, and commonly used agents for the empiric treatment of febrile neutropenia are not active against this organism. This indicates that most oncology patients who present with this infection would not receive appropriate initial treatment. In addition, antibiotic therapy may need to be modified, based on drug availability.. B. cepacia is an emerging multidrug-resistant pathogen that can produce severe infection in immunocompromised patients. It is pertinent to consider this organism in oncology patients who do not improve with standard therapy, as prompt use of correct pharmacotherapy is necessary to avoid serious morbidity as well as mortality in this population.

Topics: Anemia, Aplastic; Anti-Bacterial Agents; Bone Marrow Transplantation; Burkholderia cepacia; Burkholderia Infections; Ceftazidime; Child; Drug Therapy, Combination; Graft vs Host Disease; Humans; Male; Minocycline; Sepsis

Unregulated inflammation underlies many diseases, including sepsis. Much interest lies in targeting anti-inflammatory mechanisms to develop new treatments. One such target is the anti-inflammatory protein annexin A1 (AnxA1) and its receptor, FPR2/ALX. Using intravital videomicroscopy, we investigated the role of AnxA1 and FPR2/ALX in a murine model of endotoxin-induced cerebral inflammation [intraperitoneal injection of lipopolysaccharide (LPS)]. An inflammatory response was confirmed by elevations in proinflammatory serum cytokines, increased cerebrovascular permeability, elevation in brain myeloperoxidase, and increased leukocyte rolling and adhesion in cerebral venules of wild-type (WT) mice, which were further exacerbated in AnxA1-null mice. mRNA expression of TLR2, TLR4, MyD-88, and Ly96 was also assessed. The AnxA1-mimetic peptide, AnxA1(Ac2-26) (100 μg/mouse, ∼33 μmol) mitigated LPS-induced leukocyte adhesion in WT and AnxA1-null animals without affecting leukocyte rolling, in comparison to saline control. AnxA1(Ac2-26) effects were attenuated by Boc2 (pan-FPR antagonist, 10 μg/mouse, ∼12 nmol), and by minocycline (2.25 mg/mouse, ∼6.3 nmol). The nonselective Fpr agonists, fMLP (6 μg/mouse, ∼17 nmol) and AnxA1(Ac2-26), and the Fpr2-selective agonist ATLa (5 μg/mouse, ∼11 nmol) were without effect in Fpr2/3(-/-) mice. In summary, our novel results demonstrate that the AnxA1/FPR2 system has an important role in effecting the resolution of cerebral inflammation in sepsis and may, therefore, provide a novel therapeutic target.

Topics: Animals; Annexin A1; Brain; Cell Adhesion; Cerebrovascular Circulation; Cytokines; Gene Expression; Inflammation; Injections, Intraperitoneal; Leukocyte Rolling; Leukocytes; Lipopolysaccharides; Lymphocyte Antigen 96; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Video; Minocycline; Oligopeptides; Peptide Fragments; Receptors, Formyl Peptide; Reverse Transcriptase Polymerase Chain Reaction; Sepsis; Toll-Like Receptors

A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Aza Compounds; Biological Availability; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Injections, Intravenous; Mice; Microbial Sensitivity Tests; Rats; Rats, Sprague-Dawley; Sepsis; Streptococcal Infections; Structure-Activity Relationship; Tetracycline Resistance; Tetracyclines

Postoperative cognitive dysfunction (POCD) is reported to occur frequently after all types especially cardiac surgery in elderly patients. It can be short-term or long-term and some cases even develop into Alzheimer's disease (AD). Although multi-risk factors associated with POCD have been identified, the etiology and pathophysiological mechanisms of this surgical complication remain elusive. Therefore, developing strategies for preventing or treating POCD is still challenging. However, increasing evidence suggests that central and systemic inflammation triggered by surgery likely plays a fundamental role in POCD developing and progression. Minocycline, a tetracycline derivative with anti-inflammatory properties, has been shown to be effective in treating neuroinflammatory related conditions or neurodegenerative diseases such as AD, Parkinson's disease, Huntington's disease. Considering that inflammation may be a potential factor of POCD and minocycline is effective in improving cognitive dysfunction induced by inflammation, we hypothesize that minocycline may be useful to treat/prevent the POCD development after surgery in elderly patients.

Topics: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Brain Diseases; Cognition Disorders; Humans; Inflammation; Minocycline; Models, Theoretical; Neurodegenerative Diseases; Postoperative Complications; Sepsis; Tetracycline; Treatment Outcome

Topics: Amylases; Anti-Bacterial Agents; Child; Enterobacter cloacae; France; Gram-Positive Bacterial Infections; Humans; Lipase; Male; Minocycline; Pancreatitis, Acute Necrotizing; Sepsis; Tigecycline

Cancer patients with complicated infections following abdominal surgery represent one of the worst clinical scenarios that is useful for testing the efficacy of empirical antimicrobial therapy. No study so far has evaluated the performance of tigecycline (TIG) when administered as empirical first-line treatment in a homogeneous population of surgical cancer patients with a febrile episode. An observational review of the data records of 24 sequential patients receiving TIG for a febrile episode following a major abdominal procedure in a single cancer institute was performed. Large bowel surgery represented 68% of all procedures, followed by gastric surgery (16%) and urinary-gynaecologic-biliary surgery (16%). Complications following surgery were observed in 68% of febrile episodes, with peritonitis and sepsis accounting for 59% and 24% of complications, respectively. Eight patients needed repeat surgery for source control. The mean duration of TIG treatment was 8 days. Causative pathogens were detected in 16 episodes (64%), and a total of 44 microorganisms were recovered (29% Escherichia coli, 9% Enterococcus faecalis and 9% coagulase-negative staphylococci). TIG was effective in 12 episodes (48%). The success rate was 67% when infectious episodes sustained by intrinsically resistant bacteria and fungi were excluded. Treatment failure was associated with the presence of complications and with microbiologically documented infection. TIG may be useful as a first-line treatment option in cancer patients requiring antibiotic treatment following surgery when complications are not present or suspected on clinical grounds and when local microbial epidemiology shows a low incidence of primary resistant bacteria.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Enterococcus faecalis; Escherichia coli; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Minocycline; Neoplasms; Peritonitis; Sepsis; Staphylococcus; Surgical Wound Infection; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Sepsis; Serum; Tigecycline; Urinary Tract Infections; Urine

Elizabethkingia miricola is a Gram-negative rod that was initially isolated from condensation water of the space station Mir. This is the 1st reported case of human disease caused by this organism.

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lymphoma, Mantle-Cell; Male; Middle Aged; Minocycline; Ofloxacin; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sepsis; Stem Cell Transplantation; Tigecycline

Dentists generally recognize the importance of periodontal treatment in patients with leukemia, with the most attention paid to preventing the development of odontogenic infection. For physicians, the worst type of infection is one caused by multidrug-resistant bacteria. Here, we report a patient with an abnormal increase in multidrug-resistant opportunistic bacteria in the gingiva during hematopoietic cell transplantation (HCT).. A 53-year-old woman receiving HCT for leukemia had an insufficient blood cell count for invasive periodontal treatment before HCT. Even brushing caused difficulties with hemostasis. Therefore, frequent pocket irrigation and local minocycline administration were performed.. The multidrug-resistant opportunistic bacterium Stenotrophomonas maltophilia was detected first in phlegm 2 days before HCT, and it was detected in a gingival smear and a blood sample 7 and 11 days after HCT, respectively. The patient developed sepsis on day 11 and died 14 days after HCT. Frequent irrigation and local antibiotic application were ineffective against S. maltophilia on the gingiva. Inflammatory gingiva without scaling and root planing showed bleeding tendency, and this interfered with the eradication of this bacterium.. The gingiva in patients undergoing leukemia treatment acts as sites of proliferation and reservoirs for multidrug-resistant opportunistic bacteria. Severe systemic infection by multidrug-resistant bacteria in such patients with leukemia also may involve the gingiva. To prevent abnormal increases in such bacteria on the gingiva, scaling and/or root planing before chemotherapy, which reduces bleeding on brushing during the neutropenic period caused by chemotherapy, may contribute to infection control in such patients, although it was impossible in this case.

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Drug Resistance, Multiple, Bacterial; Fatal Outcome; Female; Gingival Diseases; Gingivitis; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Middle Aged; Minocycline; Opportunistic Infections; Periodontitis; Povidone-Iodine; Sepsis; Stenotrophomonas maltophilia; Transplantation Conditioning; Whole-Body Irradiation

Adequate antimicrobial therapy is crucial for the survival of critically ill patients with severe nosocomial infections. Tigecycline, the first available agent in the new class of glycylcyclines, is active against multiresistant gram-positive and gram-negative bacteria. The aim of this observational, retrospective evaluation was to assess tigecycline use patterns in a surgical intensive care unit (SICU) of a tertiary care centre.. Data from 70 patients receiving tigecycline in the SICU were analysed. We reviewed tigecycline use in terms of demographic data and co-morbidities, disease severity, clinical indication, microbiology, therapy regimens and mortality. A logistic regression analysis was performed to identify prognostic factors for mortality.. The majority of patients had co-morbidities such as cancer (51%) or renal replacement therapy (57%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of patients at admission was 27. Intra-abdominal infection was most frequently diagnosed (50% of patients); intra-abdominal infection and pneumonia were diagnosed in 14%. Methicillin-resistant Staphylococcus aureus was found in 16% of patients (colonization; infection: 6%) and vancomycin-resistant enterococci in 27% (colonization; infection: 21%). The mean duration of tigecycline therapy was 9 +/- 4 days; 76% of patients received tigecycline in combination, with 64% being treated second line. APACHE score and renal replacement were identified as predictive factors for mortality. SICU mortality was 30%.. Tigecycline treatment of critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality. Tigecycline may be an important treatment option for septic patients with infections resistant to other available agents.

Topics: Aged; Critical Care; Drug Evaluation; Female; Humans; Intensive Care Units; Male; Middle Aged; Minocycline; Retrospective Studies; Sepsis; Shock, Septic; Tigecycline; Treatment Outcome

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections with certain types of bacteria and fungi. Presented herein is the case of a 29 year old woman with CGD who suffered from bacteria-associated haemophagocytic syndrome and a septic pulmonary embolism following a uterine infection and sepsis, caused by Burkholderia cepacia complex.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Burkholderia cepacia complex; Burkholderia Infections; Echinocandins; Female; Granulomatous Disease, Chronic; Humans; Lipopeptides; Lipoproteins; Lymphohistiocytosis, Hemophagocytic; Micafungin; Minocycline; Peptides, Cyclic; Pulmonary Embolism; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Streptomyces species are part of the actinomycetes group. They have rarely been reported as a cause of invasive infection. We report a case of catheter-related Streptomyces bacteremia complicated by severe sepsis and septic thrombosis. We also present a brief review of the literature on Streptomyces bacteremia.

Topics: Aged; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Catheterization, Central Venous; Fluoroquinolones; Humans; Male; Minocycline; Moxifloxacin; Quinolines; Sepsis; Streptomyces; Treatment Outcome; Venous Thrombosis

A 35-year-old female with malabsorption syndrome who underwent a pancreatoduodenectomy for multiple endocrine adenomatosis 13 years prior was admitted to our hospital with diarrhea, general fatigue, high fever, and eruption in the lower legs. The patient had consumed raw shrimp a few days before onset and presented systemic inflammatory response syndrome at the time of hospitalization. Vibrio vulnificus was isolated from a blood culture performed before admission to the intensive care unit. We excised necrotizing tissue in the legs after improvement of her general condition. During the treatment process, glucose, catecholamine, and appropriate antibiotics were administered for hypoglycemia, hypotension, and high fever, respectively. The patient was discharged 107 days after contracting the disease. Of 18 septic patients with V. vulnificus infection admitted to our hospital, this was the first to develop septicemia in the absence of a previous liver dysfunction. In order to prevent this type of fatal infection, public education for immuno-compromised individuals as well as those with liver disease is essential. For early diagnosis and appropriate treatment, more effective strategies are required, such as the establishment of a network system where family physicians and emergency hospital staff could discuss information regarding high-risk patients.

Topics: Adult; Anti-Bacterial Agents; Catecholamines; Ceftazidime; Drug Therapy, Combination; Fasciitis, Necrotizing; Female; Glucose; Humans; Immunocompromised Host; Malabsorption Syndromes; Minocycline; Multiple Endocrine Neoplasia Type 1; Sepsis; Treatment Outcome; Vibrio Infections; Vibrio vulnificus

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Catheterization, Central Venous; Child; Chlorhexidine; Clinical Trials as Topic; Enzyme Inhibitors; Equipment Design; Humans; Minocycline; Rifampin; Sepsis; Silver Sulfadiazine

Topics: Anti-Bacterial Agents; Antirheumatic Agents; Arteritis; Arthritis, Rheumatoid; Diagnosis, Differential; Etanercept; Fatal Outcome; Humans; Immunoglobulin G; Male; Middle Aged; Minocycline; Receptors, Tumor Necrosis Factor; Sepsis

From January 1978 to August 1990, Staphylococcus aureus bacteremia (SAB) were identified in 31 patients with hematological malignancies at Jichi Medical School hospital. Mortality due to SAB was 48.4% (15/31). Of the variables analyzed, four factors were significantly associated with a poor prognosis; elderly age (p = 0.015), high granulocyte count (more than 500/microliters) (p = 0.015), presence of DIC (p = 0.011) and presence of pneumonia (p = 0.023). The incidence of methicillin-resistant SAB was 32.3% (10/31) and the first patient developed in 1985. Although not statistically significant, there was a trend of higher mortality for methicillin-resistant SAB (70%) than for methicillin-sensitive SAB (38.1%). Most strains of methicillin-resistant Staphylococcus aureus were sensitive to minocycline, chloramphenicol and vancomycin.

Topics: Adult; Aged; Aged, 80 and over; Chloramphenicol; Female; Humans; Leukemia; Male; Methicillin Resistance; Middle Aged; Minocycline; Prognosis; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Aged; Aged, 80 and over; Arthritis, Infectious; Cloxacillin; Drug Resistance, Microbial; Female; Fosfomycin; Humans; Knee Joint; Lung Abscess; Methicillin; Minocycline; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Topics: Acupuncture Therapy; Aged; Back Pain; Cefazolin; Female; Humans; Minocycline; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Topics: Aged; Alcaligenes; Aortic Valve Insufficiency; Cross Infection; Drug Therapy, Combination; Humans; Hypertension; Male; Minocycline; Sepsis; Vancomycin

Topics: Humans; Male; Meningitis, Meningococcal; Meningococcal Infections; Middle Aged; Minocycline; Rifampin; Sepsis

Topics: Chloramphenicol; Doxycycline; Erythromycin; Humans; Leg; Lincomycin; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Penicillin Resistance; Penicillins; Pneumonia; Sepsis; Streptococcus pneumoniae; Tetracycline; Thrombophlebitis

Topics: Antibody Formation; Antigens, Bacterial; Bacterial Vaccines; Carrier State; Disease Outbreaks; Humans; Immunization; Immunotherapy; Meningitis, Meningococcal; Meningococcal Infections; Military Medicine; Minocycline; Neisseria meningitidis; Polysaccharides, Bacterial; Rifampin; Sepsis; Sulfadiazine; United States