minocycline and Staphylococcal-Infections

Tigecycline, a derivative of minocycline, is an extended-spectrum antimicrobial agent. It has a restricted approval field in children and the experience of its adoption in clinical practice is reserved for cases of challenging infections. The aim of this review was to summarize evidence regarding the use of tigecycline in infants and children, focusing on the drug's clinical efficacy data and tolerability profile. Areas covered: We have conducted a literature search of the Cochrane Library, EMBASE, and MEDLINE databases, from their inception through 5 January 2017, using the following terms: tigecycline, newborn, infant, child, pediatrics, adolescent, human, clinical trial, and case report. Articles were excluded if they were redundant or not pertinent. Bibliographies of all relevant articles were also evaluated. Seventeen publications were included: 1 pharmacokinetic study, 16 case reports. In the selected publications, the patients' mean age was 4.45 years, 38.7% of children was <3 years old and favorable clinical response was achieved in 74.2% of cases. Expert commentary: Tigecycline may be a considerable option in life-threatening infections in pediatric patients. Its administration is well tolerated and has demonstrated a good clinical response in nonbacteremic patients. However, the available clinical records are limited and more studies are needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Infant; Infant, Newborn; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tigecycline; Treatment Outcome

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with increased morbidity, mortality and length of hospital stay. MRSA is a major pathogen in hospitals and an important pathogen in community infections with few severe and fatal cases. However, MRSA causes the majority of skin and soft tissue infections in the US. The burden of community MRSA is much smaller in Europe, but there are reports of livestock-associated MRSA (LA-MRSA) isolated from pigs and cattle causing significant infections in the people who are connected to these farms. MRSA has been present in Croatia for more than 45 years, and it exerts a different impact on health-care infections. A remarkable increase in MRSA percentage was noted in primarily sterile samples in 2002 (37%) in comparison to 2001 (31%). This percentage remained quite high until 2008, when the first signs of a reduced trend were observed. The lowest percentage was 22% in 2012.

Topics: Animals; Anti-Bacterial Agents; Carrier State; Cattle; Croatia; Daptomycin; Humans; Linezolid; Livestock; Methicillin-Resistant Staphylococcus aureus; Minocycline; Prevalence; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Swine; Teicoplanin; Tigecycline; Vancomycin; Zoonoses

New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options. Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin). Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development. This review focuses on discussing these newer antibiotics used in the "post-vancomycin" era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Cephalosporins; Daptomycin; Drug Resistance, Multiple, Bacterial; Drugs, Investigational; Genes, Bacterial; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; Tigecycline; Vancomycin

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

After the report of first case of methicillin-resistant Staphylococcus aureus (MRSA) in 1961, MRSA become a major problem worldwide. Over the last decade MRSA strains have emerged as serious pathogens in nosocomial and community settings. Glycopeptides (vancomycin and teicoplanin) are still the current mainstay of therapy for infections caused by MRSA. In the last decade dramatic changes have occurred in the epidemiology of MRSA infections. The isolates with reduced susceptibility and in vitro resistance to vancomycin have emerged. Recently, therapeutic alternatives such as quinupristin/dalfopristin, linezolid, tigecycline and daptomycin have been introduced into clinical practice for treating MRSA infections. Nevertheless, these drugs are only approved for certain indication and resistance has already been reported. In this review, the new information on novel drugs for treating MRSA infections and the resistance mechanisms of these drugs were discussed.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Protein Synthesis Inhibitors; Staphylococcal Infections; Teicoplanin; Tigecycline; Vancomycin; Vancomycin Resistance; Virginiamycin

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 epidemiology of nosocomial and community-acquired infections has changed in recent years. Methicillin-resistant Staphylococcus aureus (MRSA), especially community-associated MRSA (CA-MRSA), has emerged as a gram-positive organism with an increasing impact in clinical practice. Infections with Acinetobacter baumannii have become a major cause of morbidity and mortality. Minocycline has significant in vitro activity against MRSA and A. baumannii that is comparable with agents currently used against these organisms. The absence of an intravenous (i.v.) minocycline formulation in recent years has limited its use in seriously ill patients infected with these organisms. However, minocycline i.v. has recently been reintroduced to the US market. The objective of this study was to review available information on the chemistry, mechanism of action, in vitro activity, resistance mechanisms, pharmacokinetics, tolerability and efficacy of minocycline against MRSA and A. baumannii. This article provides suggestions for future studies and potential uses of minocycline and is designed to trigger interest in systematic clinical evaluation of minocycline for patients infected with these organisms. In conclusion, minocycline is an old drug that has the potential to become an important part of the armamentarium against emerging infections such as CA-MRSA and A. baumannii. Owing to its promising profile against these clinically important pathogens as well as excellent pharmacokinetic properties, minocycline merits evaluation in serious infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; United States

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin Resistance

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; Clindamycin; Community-Acquired Infections; Daptomycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluoroquinolones; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tetracyclines; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Vancomycin

We review data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). In this review, we cover findings reported in the English language medical literature up to February 2006. Despite the emergence of resistant and multidrug resistant S. aureus, five effective drugs for which little resistance has been observed are in clinical use: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline, and daptomycin. However, vancomycin is less effective for infections with MRSA isolates that have a high minimum inhibitory concentration in the susceptible range. Linezolid looks promising in the treatment of MRSA pneumonia and skin and soft-tissue infections (SSTIs). Daptomycin displays rapid bactericidal activity in vitro, and it has been shown to be noninferior to comparator agents in the treatment of SSTIs and bacteremia. Tigecycline was also noninferior to comparator drugs in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole, doxycycline, and minocycline are oral antistaphylococcal agents that may have utility in the treatment of SSTIs and osteomyelitis, but the clinical data for their efficacy is limited. There are four drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of clinical testing: ceptobiprole and three new glycopeptides with potent bactericidal activity, oritavancin, dalbavancin, and telavancin. Thus, there are currently many effective drugs to treat resistant S. aureus infections and many promising agents in the pipeline. Nevertheless, S. aureus remains a formidable adversary against which there are frequent treatment failures. The next goals are to determine the most appropriate indications and cost-effectiveness of each of these drugs in the treatment strategy against S. aureus.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Linezolid; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin; Virginiamycin

The advent of vancomycin-resistant enterococci in the 1990s and the threat posed by vancomycin resistance in Staphylococcus aureus led to the development of several new antimicrobial agents active against these pathogens. Quinupristin/dalfopristin was the first such drug to be commercially available but adverse effects have meant that the drug is now rarely used. Linezolid, the first antimicrobial of the oxazolidinone class, has met with more widespread use and has both an intravenous and an oral formulation. Daptomycin is a lipopeptide antimicrobial that is rapidly bactericidal against S. aureus. It is effective in the therapy of S. aureus bloodstream infections but is inactivated by pulmonary surfactant, making it of no use in the therapy of pneumonia. Tigecycline, by contrast, is bacteriostatic against most pathogens but has a broad spectrum of antimicrobial activity and has enhanced penetration into many tissues. Other new antibiotics (dalbavancin, telavancin, ceftobiprole and doripenem) are currently under clinical development and hold promise for widespread clinical use in the next decade.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Infections; Daptomycin; Humans; Linezolid; Minocycline; Oxazolidinones; Staphylococcal Infections; Streptococcal Infections; Tigecycline; Virginiamycin

Nitrofurantoin, amikacin, colistin, polymyxin B, doxycycline, and minocycline are antibiotics with proven effectiveness against selected pathogens. These antibiotics have not developed resistance over time. As "low-resistance potential antibiotics" that are effective against an increasing number of infections due to resistant gram-positive or gram-negative pathogens, these antimicrobials remain an important part of the antibiotic armamentarium. They will be used increasingly in the future, as highly resistant organisms continue to be important clinically and therapeutic options remain limited.

Topics: Amikacin; Cell Membrane; Colistin; Doxycycline; Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Humans; Methicillin Resistance; Minocycline; Nitrofurantoin; Polymyxin B; Staphylococcal Infections; Urinary Tract Infections

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

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

This paper reviews recent data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review will focus on new findings reported in the English-language medical literature from June 2003 to September 2004.. Despite the emergence of resistant and multidrug-resistant S. aureus, we have three effective drugs in clinical use for which little resistance has been observed: quinupristin-dalfopristin, linezolid, and daptomycin. Linezolid looks particularly promising in the treatment of MRSA pneumonia. Daptomycin displays rapid bactericidal activity in vitro, but, so far, clinical trials have only been conducted for the treatment of skin and soft-tissue infections. There are three drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of testing: two new glycopeptides with potent bacteriocidal activity and long half-lives (oritavancin and dalbavancin), and tigecycline, a minocycline derivative. These drugs have also shown efficacy in the treatment of skin and soft-tissue infections.. The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Virginiamycin

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

Topics: Anti-Bacterial Agents; Cefmetazole; Cephamycins; Drug Therapy, Combination; Fosfomycin; Humans; Methicillin; Minocycline; Ofloxacin; Oxazines; Penicillin Resistance; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus epidermidis; Tetracyclines

A randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistant Staphylococcus aureus (MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U.S. sites. Patients suspected or documented to have infections caused by Gram-negative bacteria were given aztreonam (2 g i.v. every 12 h [q12h]) if randomized to linezolid or matching placebo infusions if randomized to omadacycline. Adverse events were reported in 46 (41.4%) omadacycline-treated and 55 (50.9%) linezolid-treated patients. Adverse events related to treatment were assessed by investigators in 24 (21.6%) omadacycline-treated and 33 (30.6%) linezolid-treated patients. The gastrointestinal tract was most commonly involved, with adverse events reported in 21 (18.9%) patients exposed to omadacycline and 20 (18.5%) exposed to linezolid. Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, -1.7 to 11.3). For microbiologically evaluable (ME) patients with S. aureus infections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.

Topics: Acetamides; Adolescent; Adult; Aged; Anti-Bacterial Agents; Aztreonam; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Oxazolidinones; Placebos; Skin; Skin Diseases, Bacterial; Staphylococcal Infections; Treatment Outcome

To determine the efficacy of minocycline-rifampin-coated hemodialysis catheters in reducing catheter-related infections in patients requiring hemodialysis for acute renal failure.. Between May 2000 and March 2002, 66 patients were randomly assigned to receive a minocycline-rifampin-impregnated central venous catheter and 64 were randomly assigned to receive an unimpregnated catheter. Patients were followed prospectively until the catheter was removed. Catheter-related infection was determined through quantitative catheter cultures, quantitative blood cultures, or both.. Both groups of patients were similar in age, sex, underlying disease, type of dialysis (continuous vs. intermittent), neutropenia during catheterization and its duration, catheter insertion difficulties, and administration of blood products or medication. The mean (+/- SD) catheter dwell time was the same in both groups (8 +/- 6 days, P = 0.7). There were seven catheter-related infections (11%), all associated with the use of unimpregnated catheters. Kaplan-Meier estimates for the risk of catheter-related infection showed that coated catheters were less likely to be associated with infection (P = 0.006).. The use of polyurethane hemodialysis catheters impregnated with minocycline and rifampin decreases the risk of catheter-related infection in patients with acute renal failure.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antibiotics, Antitubercular; Catheterization, Central Venous; Drug Therapy, Combination; Female; Humans; Male; Methicillin Resistance; Middle Aged; Minocycline; Polyurethanes; Prospective Studies; Renal Dialysis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Time Factors

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

Topics: Catheterization; Drug Therapy, Combination; Humans; Long-Term Care; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Nasal Cavity; Pilot Projects; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

The antistaphylococcal properties of orally administered minocycline and penicillin-V were compared for one hundred and fifteen patients receiving minocycline and one hundred and twenty-eight receiving penicillin-V for various types of cutaneous infections. The majority of bacterial isolates were staphylococcal organisms. Of these 82 percent showed initial in vitro sensitivity to minocycline while only 20 percent did to penicillin-V. The percentage of clinical cures was higher with minocycline (74 percent) than with penicillin-V (54 percent), however, most patients, in both groups, showed clinical improvement. The rate of clinical improvement appeared to be significantly faster with minocycline. There was a higher percentage of adverse, chiefly vestibular, effects in the minocycline group (16 percent vs 7 percent). The study clearly demonstrates the superior antistaphylococcal properties of minocycline as compared with penicillin-V.

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Minocycline; Penicillin Resistance; Penicillin V; Skin Diseases, Infectious; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines

The genus

Topics: Animals; Anti-Bacterial Agents; Artocarpus; Biofilms; Flavonoids; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Bacterial contamination and biofilm formation onpercutaneous implants can lead to device failure and be life-threatening. To solve this issue, we constructed a carboxymethyl dextran- (CMD-) based nanomicelle antibacterial coating on the microarc-oxidized titanium (MAO-Ti) surface (described in the supplementary file). The self-assembled CMD-based nanomicelles and octadecylamine (ODA) were developed as a drug carrier and loaded with minocycline (MC). The characterization and stability of the MC-loaded nanomicelles were determined. The surface roughness, hydrophilicity, and drug release property of the coatings were also investigated. Our findings showed that the cross-linked MC-loaded nanomicelles (MC@(ODA-CMD)

Topics: Anti-Bacterial Agents; Coated Materials, Biocompatible; Dextrans; Drug Liberation; Humans; Minocycline; Monoamine Oxidase; Staphylococcal Infections; Staphylococcus aureus; Surface Properties; Titanium

To determine the frequency and antibiotic susceptibility pattern of CA-MRSA in patients with uncomplicated skin and soft tissue infections reporting to the dermatology outpatient of a tertiary health care hospital.. A descriptive study.. Dermatology outpatient of a tertiary care hospital in Punjab province of Pakistan, from September 2020 to August 2021.. Patients of all age groups and both genders reporting during the study period with community-associated uncomplicated bacterial skin and soft tissue infections were enrolled in the study. Samples were collected from skin lesions and cultured on blood agar and MacConkey agar plates. Antimicrobial susceptibility testing using the modified Kirby Baur disc diffusion technique was performed.. A total of 157 patients were included in the study. Impetigo was most common infection (n=80, 51%), followed by Furunculosis (n=47, 29.9%). The frequency of MRSA isolates was 54.1% (n=85). MRSA was significantly more frequently isolated from patients with furunculous, carbuncle and cutaneous abscesses as compared to impetigo. All MRSA isolates were sensitive to linezolid, teicoplanin, and vancomycin. 97.6%, 84.7%, and 72.9% of MRSA isolates were sensitive to rifampicin, minocycline, and fusidic acid respectively. 89.4% of MRSA were sensitive to amikacin and clindamycin. 63.5% were sensitive to doxycycline and 58.8% were sensitive to co-trimoxazole. Only 20% of MRSA were sensitive to ciprofloxacin.. The antibiotics active against CA-MRSA including rifampicin, minocycline, amikacin, and clindamycin may be used empirically in patients with furunculosis, cutaneous abscess, and carbuncles. Linezolid, teicoplanin, and vancomycin should be reserved for severe infections.. Uncomplicated skin and soft tissue infections, Community-associated Methicillin-resistant staphylococcus aureus (CA-MRSA), Antibiotic susceptibility pattern.

Topics: Agar; Amikacin; Animals; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Female; Furunculosis; Humans; Impetigo; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Rifampin; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Teicoplanin; Vancomycin

Tetracyclines are widely used as oral therapy of MRSA infection, however, the pharmacodynamic underpinning is absent.. We employed an in vitro pharmacokinetic model to study the pharmacodynamics of minocycline alone and in combination with rifampicin.. An exposure-ranging design was used to establish fAUC/MIC targets for static, -1 log drop and -2 log drop effects against Staphylococcus aureus for minocycline and in combination with rifampicin. We then simulated 7-10 day human dosing of minocycline and the combination.. The minocycline fAUC/MIC for 24 h static effect and -1 log drop in bacterial load were 12.5 ± 7.1 and 23.3 ± 12.4. fAUC/MIC targets for static and -1 log drop were greater at 48 and 72 h. The addition of simulated free rifampicin associated with dosing 300 mg q12h reduced the 24 h minocycline fAUC/MICs. Simulations performed over 7-10 days exposure indicated that for minocycline standard human doses there was a 1-3 log reduction in viable count and no changes in population profiles. Addition of rifampicin resulted in larger reductions in staphylococcal load but emergence of resistance to rifampicin. There was no resistance to minocycline.. An fAUC/MIC minocycline target of 12-36 is appropriate for S. aureus. Addition of rifampicin decreases bacterial load but results in emergence of resistance to rifampicin. Unusually, there was no emergence of resistance to minocycline.

Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Acinetobacter baumannii; Acinetobacter Infections; Alginates; Animals; Anti-Bacterial Agents; Burns; Female; Gentamicins; Hydrogels; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Swine; Vancomycin; Wound Healing; Wound Infection

Topics: Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; HIV Infections; Homosexuality, Male; Humans; Japan; Male; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Scrotum; Staphylococcal Infections; Treatment Outcome; Ulcer

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

A tigecycline-susceptible (TGC-S) Sequence Type (ST) 5 clinical methicillin-resistant Staphylococcus aureus (MRSA) strain was cultured in escalating levels of tigecycline, yielding mutants eightfold more resistant. Their genomes were sequenced to identify genetic alterations, resulting in resistance. Alterations in rpsJ, commonly related to tigecycline resistance, were also investigated. Tigecycline resistance was mediated by loss-of-function mutations in the transcriptional repressor mepR, resulting in derepression of the efflux pump mepA. Increased levels of resistance were obtained by successive mutations in mepA itself. No alterations in RpsJ were observed in selected strains, but we observed a K57M substitution, previously correlated with resistance, among TGC-S clinical strains. Thus, the pathway to tigecycline resistance in CC5 MRSA in vitro appears to be derepression of mep operon as the result of mepR loss-of-function mutation, followed by alterations in MepA efflux pump. This shows that other evolutionary pathways, besides mutation of rpsJ, are available for evolving tigecycline resistance in CC5 MRSA.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Genome, Bacterial; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Mutation; Staphylococcal Infections; Tigecycline

Clonal complex (CC) 9 is a prevalent livestock-associated (LA) MRSA clone in Asia whose pathogenicity in humans remains unknown.. In 2012, we identified a patient with CC9-MRSA infection linked to livestock. After screening 3328 clinical MRSA isolates from a national database, eight isolates (0.24%) collected between 1998 and 2012 were further confirmed to be of CC9. The detailed molecular features of the nine human CC9 strains and phylogenetic relatedness to animal CC9 strains were characterized with WGS. The antibiotic susceptibilities were determined and the clinical information was abstracted from medical records.. WGS grouped the CC9 strains into two clades, which were respectively associated with distinct toxome profiles, resistance gene profiles and staphylococcal cassette chromosomes (SCCmecXII for 7 isolates and SCCmecVT for 2 isolates). The SCCmecXII strains were phylogenetically related to animal CC9-MRSA strains, negative for Panton-Valentine leucocidin and 100% resistant to ciprofloxacin, erythromycin, clindamycin, gentamicin and tigecycline. Four of the seven SCCmecXII isolates were associated with invasive diseases including bacteraemia leading to death (2) and osteomyelitis (2). Two SCCmecXII isolates were from patients with exposure to pigs before development of the MRSA diseases.. The CC9-SCCmecXII MRSA prevailing in pigs in Asia is multidrug resistant and potentially pathogenic to humans. It is critical to continuously monitor the local epidemiology of MRSA and implement effective control measures to limit the spread of LA-MRSA between animals, to humans and in healthcare facilities.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Child, Preschool; Ciprofloxacin; Clindamycin; Drug Resistance, Multiple, Bacterial; Erythromycin; Farmers; Female; Gentamicins; Humans; Livestock; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Swine; Swine Diseases; Taiwan; Tigecycline; Virginiamycin

Injuries to the skin are often complicated by invasive infections. Standard treatment with intravenous antibiotics has limited tissue penetration and sometimes, major systemic toxicity. Traditional topical delivery of antimicrobials also has limited effectiveness and duration of action. We demonstrate the use of a new Platform Wound Device (PWD) for delivery of topical, ultrahigh concentrations of minocycline as well as lidocaine onto the burn eschar and on the surface of excisional wounds in a total of 56 burn wounds and 24 excisional wounds in a porcine model. Wounds were created on day 0, debrided on day 3, and pigs were killed on day 7. After 3 days of PWD with minocycline treatment, bacterial count was 5.44 log CFU/g in dorsal wound tissue inoculated with methicillin-resistant Staphylococcus aureus, less than that after treatment with silver sulfadiazine cream (7.64 log CFU/g). Pain was also relieved or eliminated in burn wounds and full-thickness excisional wounds when lidocaine was delivered by the PWD. The results demonstrate that ultrahigh concentrations of antibiotics can be delivered effectively by the PWD, and will accelerate wound bed preparation.

Topics: Administration, Topical; Anesthetics, Local; Animals; Anti-Bacterial Agents; Bacterial Load; Burns; Debridement; Disease Models, Animal; Female; Lidocaine; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; Swine; Wound Healing; Wound Infection

This study aims the in vivo biological characterization of an innovative minocycline delivery system, based on polymethylmethacrylate bone cement. Bone cements containing 1% or 2.5% (w/w) minocycline were formulated and evaluated through solid-state characterization. Biological evaluation was conducted in vivo, within a rat model, following the subcutaneous and bone tissue implantation, and tissue implantation associated with Staphylococcus aureus is challenging. The assessment of the tissue/biomaterial interaction was conducted by histologic, histomorphometric and microtomographic techniques. Minocycline addition to the composition of the polymethylmethacrylate bone cement did not modify significantly the cement properties. Drug release profile was marked by an initial burst release followed by a low-dosage sustained release. Following the subcutaneous tissue implantation, a reduced immune-inflammatory reaction was verified, with diminished cell recruitment and a thinner fibro-connective capsule formation. Minocycline-releasing cements were found to enhance the bone-to-implant contact and bone tissue formation, following the tibial implantation. Lastly, an effective antibacterial activity was mediated by the implanted cement following the tissue challenging with S. aureus. Kinetic minocycline release profile, attained with the developed polymethylmethacrylate system, modulated adequately the in vivo biological response, lessening the immune-inflammatory activation and enhancing bone tissue formation. Also, an effective in vivo antibacterial activity was established. These findings highlight the adequacy and putative application of the developed system for orthopedic applications.

Topics: Animals; Anti-Bacterial Agents; Bone Cements; Drug Delivery Systems; Drug Implants; Male; Minocycline; Polymethyl Methacrylate; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus

To evaluate microbiological effectiveness, that is, culture negativity of a non-blinded eradication protocol (Rx) compared with observation (Obs) in clinically stable cystic fibrosis participants with newly positive methicillin resistant. This non-blinded trial randomised participants ages 4-45 years with first or early (≤2 positive cultures within 3 years) MRSA-positive culture without MRSA-active antibiotics within 4 weeks 1:1 to Rx or Obs. The Rx protocol was: oral trimethoprim-sulfamethoxazole or if sulfa-allergic, minocycline plus oral rifampin; chlorhexidine mouthwash for 2 weeks; nasal mupirocin and chlorhexidine body wipes for 5 days and environmental decontamination for 21 days. The primary end point was MRSA culture status at day 28.. Between 1 April 2011 to September 2014, 45 participants (44% female, mean age 11.5 years) were randomised (24 Rx, 21 Obs). At day 28, 82% (n=18/22) of participants in the Rx arm compared with 26% (n=5/19) in the Obs arm were MRSA-negative. Adjusted for interim monitoring, this difference was 52% (95% CI 23% to 80%, p<0.001). Limiting analyses to participants who were MRSA-positive at the screening visit, 67% (8/12) in the Rx arm and 13% (2/15) in the Obs arm were MRSA-negative at day 28, adjusted difference: 49% (95% CI 22% to 71%, p<0.001). Fifty-four per cent in the Rx arm compared with 10% participants in the Obs arm remained MRSA-negative through day 84. Mild gastrointestinal side effects were higher in the Rx arm.. This MRSA eradication protocol for newly acquired MRSA demonstrated microbiological efficacy with a large treatment effect.. NCT01349192.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Child; Child, Preschool; Chlorhexidine; Cystic Fibrosis; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The goals of the current study were to determine the in vitro antibacterial activity of tigecycline against multiple clinically relevant ocular pathogens and to evaluate the in vivo ocular tolerability and efficacy of 0.5% tigecycline in a methicillin-resistant Staphylococcus aureus (MRSA) keratitis model.. In vitro: Minimum inhibitory concentrations (MICs) were determined for 110 clinical conjunctivitis isolates, 26 keratitis isolates of Pseudomonas aeruginosa, and 10 endophthalmitis isolates each of MRSA, methicillin-susceptible S. aureus (MSSA), MR, and MS coagulase-negative Staphylococcus.. Six uninfected rabbits were topically treated in both eyes with 0.5% tigecycline, vehicle, or saline every 15 min for 3 h.. Thirty-two rabbits were intrastromally injected with 700 Colony Forming Units (CFU) of MRSA in both eyes and were separated into 4 groups (n = 8): tigecycline 0.5%; vancomycin 5%; saline; and no treatment (euthanized before treatment for baseline CFU). Four hours after MRSA challenge, topical treatment of 1 drop every 15 min for 5 h was initiated. One hour after treatment, the corneas were harvested for CFU. The data were analyzed nonparametrically.. In vitro: Tigecycline demonstrated lower MICs than the other tested antibiotics against gram-positive organisms, especially MRSA, while MICs against gram-negative pathogens, including fluoroquinolone-resistant P. aeruginosa, appeared to be in the treatable range with aggressive topical therapy.. 0.5% tigecycline was graded as minimally irritating.. 0.5% tigecycline and vancomycin produced similar reductions in CFU and were less than saline (P < 0.05). Tigecycline and vancomycin demonstrated 99.9% reductions compared with baseline CFU.. Tigecycline is a potential candidate for a topical ocular antibiotic.

Topics: Administration, Ophthalmic; Animals; Anti-Bacterial Agents; Eye Infections, Bacterial; Female; In Vitro Techniques; Keratitis; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Rabbits; Staphylococcal Infections; Tigecycline

The aim of this study was to evaluate the antimicrobial susceptibility profile of 85 Staphylococcus epidermidis and 84 Staphylococcus haemolyticus strains isolated from blood cultures to oxacillin, vancomycin, tigecycline, linezolid, daptomycin, and quinupristin/dalfopristin over a period of 12 years. S. epidermidis and S. haemolyticus isolated from blood cultures of inpatients, attended at a teaching hospital, were analyzed for the presence of the mecA gene and by SCCmec typing. The minimum inhibitory concentration (MIC) values of tigecycline, linezolid, daptomycin, quinupristin/dalfopristin, and vancomycin were determined. Isolates exhibiting vancomycin MICs of ≥2 μg/ml were typed by pulsed-field gel electrophoresis (PFGE). The rate of mecA positivity was 92.9% and 100% in S. epidermidis and S. haemolyticus, respectively. The most frequent SCCmec types were type III (53.2%) in S. epidermidis and type I (32.1%) in S. haemolyticus. All isolates were susceptible to linezolid and daptomycin, but 7.1% of S. haemolyticus and 2.3% of S. epidermidis isolates were resistant to tigecycline, and 1.2% each of S. haemolyticus and S. epidermidis were resistant and intermediately resistant to quinupristin/dalfopristin, respectively. S. epidermidis exhibited higher vancomycin MICs (40% with MIC of ≥2 μg/ml). Clonal typing of strains with vancomycin MIC of ≥2 μg/ml revealed the presence of different PFGE types of S. epidermidis and S. haemolyticus over a period of up to 4 years (2002-2004, 2005-2008, 2006-2009, 2010-2011). Despite the observation of a high prevalence of mecA, the clinical strains were fully susceptible to vancomycin and to the new drugs linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. The PFGE types with vancomycin MIC of ≥2 μg/ml exhibited a great diversity of SCCmec cassettes, demonstrating that S. epidermidis and S. haemolyticus may easily acquire these resistance-conferring genetic elements.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; Blood Culture; Brazil; Daptomycin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Hospitals, Teaching; Humans; Linezolid; Minocycline; Mutation; Oxacillin; Prevalence; Staphylococcal Infections; Staphylococcus epidermidis; Staphylococcus haemolyticus; Tigecycline; Vancomycin; Virginiamycin

Previously, we investigated a locally developed technique of bonding arterial grafts with three antimicrobials to protect against early (within 2 weeks) perioperative bacterial contamination encountered occasionally during aortic graft prosthetic reconstruction. Vascular graft infections are classified by their appearance time (early [<4 months] vs late [>4 months] after graft implantation), degree of incorporation into the surrounding vessel wall, connectivity to the postoperative wound, and extent of graft involvement. In the current phase of testing, we evaluated the ability of our novel triple antimicrobial-bonded graft to prevent infection in the first 8 weeks after implantation.. At week 9, all of the grafts were explanted. All S aureus-inoculated bonded grafts (n = 5) showed no bacterial growth. The unbonded, uninoculated graft (n = 1) showed low-level bacterial growth (<1.2 × 10. Our triple-bonded aortic graft prevented perioperative aortic graft infection for at least 8 weeks in a porcine model. The synergistic antimicrobial activity of this graft was sufficient to prevent and/or eradicate infection during that period. Further studies are needed to assess the graft's ability to combat early-onset vascular graft infection for up to 4 months.

Topics: Animals; Anti-Infective Agents; Aorta, Abdominal; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Chlorhexidine; Coated Materials, Biocompatible; Disease Models, Animal; Minocycline; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Swine; Swine, Miniature; Time Factors

Burn and blast injuries are frequently complicated by invasive infections, which lead to poor wound healing, delay in treatment, disability, or death. Traditional approach centers on early debridement, fluid resuscitation, and adjunct intravenous antibiotics. These modalities often prove inadequate in burns, where compromised local vasculature limits the tissue penetration of systemic antibiotics. Here, we demonstrate the treatment of infected burns with topical delivery of ultrahigh concentrations of antibiotics. Standardized burns were inoculated with Staphylococcus aureus or Pseudomonas aeruginosa. After debridement, burns were treated with either gentamicin (2 mg/mL) or minocycline (1 mg/mL) at concentrations greater than 1,000 times the minimum inhibitory concentration. Amount of bacteria was quantified in tissue biopsies and wound fluid following treatment. After six days of gentamicin or minocycline treatment, S. aureus counts decreased from 4.2 to 0.31 and 0.72 log CFU/g in tissue, respectively. Similarly, P. aeruginosa counts decreased from 2.5 to 0.0 and 1.5 log CFU/g in tissue, respectively. Counts of both S. aureus and P. aeruginosa remained at a baseline of 0.0 log CFU/mL in wound fluid for both treatment groups. The findings here demonstrate that super-therapeutic concentrations of antibiotics delivered topically can rapidly reduce bacterial counts in infected full-thickness porcine burns. This treatment approach may aid wound bed preparation and accelerate time to grafting.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Burns; Debridement; Disease Models, Animal; Female; Gentamicins; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Swine; Wound Healing; Wound Infection

Tigecycline (TIG) is an antibiotic belonging to the glycylcyclines class and appears to be a good choice to fight infections caused by Staphylococcus aureus. To date, TIG exhibits good activity against this microorganism. The aim of this work was to obtain in vitro mutants of S. aureus resistant to TIG and evaluate possible changes in their susceptibility patterns to other antibiotics.. Two mutants of S. aureus resistant to TIG (MIC = 16 µg/mL) were selected in vitro from clinical isolates of methicillin-resistant S. aureus. In both mutants, corresponding to different lineage (ST5 and ST239), an increase of efflux activity against TIG was detected. One mutant also showed a reduced susceptibility to vancomycin, corresponding to the VISA phenotype (MIC = 4 µg/mL), with a loss of functionality of the agr locus. The emergence of the VISA phenotype was accompanied by an increase in oxacillin and cefoxitin MICs.. This study demonstrates that, under selective pressure, the increase of efflux activity in S. aureus is one of the mechanisms that may be involved in the emergence of tigecycline resistance. The emergence of this phenotype may eventually be associated to changes in susceptibility to other antibiotics such oxacillin and vancomycin.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Mutation; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin

In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Minocycline; Oligopeptides; Quorum Sensing; Staphylococcal Infections; Tigecycline; Wound Infection

Postoperative infection is a devastating complication following arthroplasty. The goals of this study were to introduce a "smart" implant coating that combines passive elution of antibiotic with an active-release mechanism that "targets" bacteria, and to use an established in vivo mouse model of post-arthroplasty infection to longitudinally evaluate the efficacy of this polymer implant coating in decreasing bacterial burden.. A novel, biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics both passively and actively. In vitro-release kinetics were studied using high-performance liquid chromatography (HPLC) quantification in conditions representing both the physiologic environment and the more oxidative, hyperinflammatory environment of periprosthetic infection. The in vivo efficacy of the PEG-PPS coating delivering vancomycin and tigecycline was tested using an established mouse model of post-arthroplasty infection. Noninvasive bioluminescence imaging was used to quantify the bacterial burden; radiography, to assess osseointegration and bone resorption; and implant sonication, for colony counts.. In vitro-release kinetics confirmed passive elution above the minimum inhibitory concentration (MIC). A rapid release of antibiotic was noted when challenged with an oxidative environment (p < 0.05), confirming a "smart" active-release mechanism. The PEG-PPS coating with tigecycline significantly lowered the infection burden on all days, whereas PEG-PPS-vancomycin decreased infection on postoperative day (POD) 1, 3, 5, and 7 (p < 0.05). A mean of 0, 9, and 2.6 × 10(2) colony-forming units (CFUs) grew on culture from the implants treated with tigecycline, vancomycin, and PEG-PPS alone, respectively, and a mean of 1.2 × 10(2), 4.3 × 10(3), and 5.9 × 10(4) CFUs, respectively, on culture of the surrounding tissue (p < 0.05).. The PEG-PPS coating provides a promising approach to preventing periprosthetic infection. This polymer is novel in that it combines both passive and active antibiotic-release mechanisms. The tigecycline-based coating outperformed the vancomycin-based coating in this study.. PEG-PPS polymer provides a controlled, "smart" local delivery of antibiotics that could be used to prevent postoperative implant-related infections.

Topics: Absorbable Implants; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Disease Models, Animal; Mice; Minocycline; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tigecycline; 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

Topics: Aged, 80 and over; Anti-Bacterial Agents; Conjunctivitis, Bacterial; Eye Infections, Bacterial; Eyelid Diseases; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; Syndrome

The objective of this study was to evaluate the antimicrobial performance of a rifampin/minocycline-coated, non-cross-linked, acellular porcine dermal matrix (XenMatrix AB) compared to an uncoated, non-cross-linked, acellular porcine dermal matrix (Strattice) after implantation/inoculation with methicillin-resistant Staphylococcus aureus or Escherichia coli in a dorsal rabbit model.. Forty male New Zealand White rabbits were bilaterally implanted with XenMatrix AB or Strattice grafts and inoculated with clinically isolated methicillin-resistant S. aureus (5 × 10 colony-forming units/ml) or E. coli (1 × 10 colony-forming units/ml). At 2 and 8 weeks, sites were analyzed for viable methicillin-resistant S. aureus/E. coli colony-forming units, abscess formation, and histologic response (n = 5 rabbits per group per bacterium per time point).. XenMatrix AB completely inhibited bacterial colonization of the graft, inhibited abscess formation, reduced inflammation and encapsulation, and improved neovascularization compared with Strattice. XenMatrix AB implants exhibited significantly fewer colony-forming units compared with Strattice implants at 2 weeks (methicillin-resistant S. aureus) (p < 0.01) and at 2 and 8 weeks (E. coli) (p < 0.05). In addition, XenMatrix AB implants demonstrated a significantly lower abscess score at 2 weeks (methicillin-resistant S. aureus) and 8 weeks (E. coli) (p < 0.01 in both cases). For both types of bacteria and both time points evaluated, XenMatrix AB implants exhibited minimal inflammation and encapsulation and a lack of neutrophils. In contrast, Strattice implants displayed marked inflammatory and neutrophilic responses and moderate encapsulation.. This study demonstrated the antimicrobial performance of a rifampin/minocycline-coated bioprosthetic (XenMatrix AB) in a rabbit inoculation model. XenMatrix AB completely inhibited bacterial colonization of the graft, with minimal host inflammation and encapsulation, and improved neovascularization compared with Strattice.

Topics: Acellular Dermis; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Escherichia coli Infections; Male; Methicillin-Resistant Staphylococcus aureus; Minocycline; Rabbits; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Swine; Treatment Outcome

Wound infection can impair postoperative healing. Topical antibiotics have potential to treat wound infection and inflammation and minimize the adverse effects associated with systemic antibiotics.. Full-thickness porcine wounds were infected with Staphylococcus aureus. Using polyurethane wound enclosure devices, wounds were treated with topical 100 μg/ml minocycline, topical 1000 μg/ml minocycline, topical saline control, or 4 mg/kg intravenous minocycline. Bacteria were quantified in wound tissue and fluid obtained over 9 hours. Immunosorbent assays were used to analyze inflammatory marker concentrations. Minocycline's effect on in vitro migration and proliferation of human keratinocytes and fibroblasts was tested using scratch assays and metabolic assays, respectively.. After 6 hours, 100 and 1000 μg/ml topical minocycline decreased bacteria in wound tissue to 3.5 ± 0.87 and 2.9 ± 2.3 log colony-forming units/g respectively, compared to 8.3 ± 0.9 log colony-forming units/g in control wounds (p < 0.001) and 6.9 ± 0.2 log colony-forming units/g in wounds treated with 4 mg/kg intravenous minocycline (p < 0.01). After 2 hours, topical minocycline reduced concentrations of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α (p < 0.01), and inflammatory cell counts in wound tissue (p < 0.05). In noninfected wounds, topical minocycline significantly reduced interleukin-1β, interleukin-6, and inflammatory cell counts after 4 hours (p < 0.01). Matrix metalloproteinase-9 concentrations decreased after 1-hour treatment (p < 0.05). Keratinocyte and fibroblast in vitro functions were not adversely affected by 10 μg/ml minocycline or less.. Topical minocycline significantly reduces bacterial burden and inflammation in infected wounds compared with wounds treated with intravenous minocycline or control wounds. Minocycline also decreases local inflammation independently of its antimicrobial effect.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Biomarkers; Female; Fibroblasts; Humans; Inflammation; Injections, Intravenous; Keratinocytes; Minocycline; Random Allocation; Staphylococcal Infections; Swine; Treatment Outcome; Wound Infection

Methicillin-resistant Staphylococcus aureus (MRSA) producing Panton-Valentine leukocidin (PVL) is highly virulent. This study aimed to compare the efficacy of tigecycline versus vancomycin in experimental thigh abscess by a PVL-producing MRSA isolate. One hundred and ninety-six Wistar rats were divided into five groups: group A, controls; groups B and C, administered vancomycin starting 1 and 6 h after bacterial challenge respectively; groups D and E, administered tigecycline starting 1 and 6 h after bacterial challenge respectively. Treatment was continued every 12 hours for three consecutive days. Survival was recorded; separate animals were killed for quantitative cultures. Serum samples were collected for estimation of malondialdehyde (MDA). Survival of group D was prolonged compared to all other groups. The bacterial load of blood, liver, spleen and lung was significantly decreased within group D compared to group B at 36 hours. Treatment with tigecycline was accompanied by significant reduction of serum MDA at 24 hours. Tigecycline is comparable to vancomycin for the treatment of soft tissue infections by PVL-producing MRSA.

Topics: Abscess; Animals; Anti-Bacterial Agents; Bacterial Load; Bacterial Toxins; Drug Administration Schedule; Exotoxins; Immunocompromised Host; Injections, Intraperitoneal; Kaplan-Meier Estimate; Leukocidins; Lipid Peroxidation; Male; Methicillin-Resistant Staphylococcus aureus; Minocycline; Random Allocation; Rats, Wistar; Soft Tissue Infections; Staphylococcal Infections; Thigh; Tigecycline; Vancomycin; Virulence

It is difficult to manage coinfections in critically ill patients, especially in the presence of mixed-species biofilms. The aim of this study was to seek an effective drug combination for managing the dual-species biofilm of Candida albicans and Staphylococcus aureus.. The interaction between fluconazole and minocycline against polymicrobial planktonic cells and polymicrobial biofilms formed over four different time intervals (4 hours, 8 hours, 12 hours, and 24 hours) was investigated using a microdilution checkerboard method. To explore whether the combined effects against the polymicrobial cultures involved calcium regulation, the effects of benidipine and ethylene glycol tetraacetic acid were characterized using a plate streaking method and a liquid-based quantitative method.. Fluconazole combined with minocycline exerted strong effects against polymicrobial planktonic cells and polymicrobial biofilms formed over 4 hours, 8 hours, and 12 hours. The addition of benidipine and ethylene glycol tetraacetic acid enhanced the activity of the drug combination, suggesting that the combined effects may involve the perturbation of calcium homeostasis.. Fluconazole in combination with minocycline is a potential approach for counteracting C. albicans-S. aureus dual-species biofilms.

Topics: Anti-Bacterial Agents; Antifungal Agents; Biofilms; Calcium; Candida albicans; Candidiasis; Coinfection; Drug Interactions; Drug Synergism; Fluconazole; Humans; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a clinically relevant pathogen because of its resistance to antibiotics and its ability to form potent biofilm. Both ica-negative as well as ica-positive MRSA strains are known to produce biofilm. In the present study, these strains were grown in biofilm mode and susceptibility of these to antibiotics was assessed. Our study suggests that antibiotic susceptibility of MRSA biofilm depends on the biochemical composition of its matrix. The biofilm matrix of ica-positive MRSA was mainly composed of poly-intercellular adhesion (PIA), whereas eDNA was a major constituent of ica-negative MRSA. The results showed that MRSA in planktonic growth was susceptible to clindamycin, vancomycin and minocycline. However, the MIC and MBC of vancomycin for the mature biofilm of ica-negative MRSA was 16 and 32 μg ml(-1), respectively. On the contrary, the MIC and MBC of vancomycin for ica-positive MRSA was >1024 μg ml(-1). The effect of vancomycin and minocycline on young and old biofilms was also determined. Vancomycin was quite effective in eradicating the young biofilm formed by ica-negative MRSA; however, it was completely ineffective on the biofilm of ica-positive MRSA. Minocycline at its highest clinical achievable concentration was found to be quite effective in eradicating the young biofilm formed by both the strains. The enzyme-linked immunosorbent assay (ELISA) results and dot blot assay suggest that the presence of ica locus influenced PIA production, which probably contributed towards the failure of vancomycin in eradicating the biofilm formed by ica-positive strain. However, none of the antibiotics used in this study was effective in eradicating the mature biofilms.

Topics: Anti-Bacterial Agents; Biofilms; Clindamycin; DNA, Bacterial; Enzyme-Linked Immunosorbent Assay; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Vancomycin

A 5-year survey (2009-2013) of antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients with bloodstream infections was carried out in Northeast Italy. No upward creep of glycopeptides MICs was documented among 582 nonduplicate MRSA blood isolates, which were tested in accordance with broth microdilution and interpreted in accordance with EUCAST recommendations. Teicoplanin showed stably a lower MIC50 in comparison with vancomycin (0.25-0.5 versus 1 mg/L). The activities of newer anti-MRSA antibacterials stratified by glycopeptides MICs showed similar trends in MICs of either vancomycin or teicoplanin with those of daptomycin, linezolid, and tigecycline. We hypothesize that in centers with different distribution of glycopeptides MICs, downward for teicoplanin and upward for vancomycin, teicoplanin could be a more effective alternative to vancomycin for empirical treatment of MRSA-related bacteremia.

Topics: Acetamides; Anti-Bacterial Agents; Blood; Daptomycin; Health Surveys; Humans; Italy; Linezolid; Longitudinal Studies; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Vancomycin

Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement.. MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50 mg/kg every 12 h, tigecycline 14 mg/kg every 12 h, rifampin 25 mg/kg every 12 h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days.. MRSA was cultured from all tibias in the control group (median, 6.06 log10 CFU/g bone). Median bacterial counts (log10 CFU/g) at 48 h post-treatment were 6.16 for vancomycin (p = 0.753), 2.29 for vancomycin plus rifampin (p < 0.001), 5.90 for tigecycline (p = 0.270), 0.10 for tigecycline plus rifampin (p < 0.001), and 0.91 for rifampin (p = 0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment.. Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Humans; Male; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Minocycline; Osteomyelitis; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tigecycline; Vancomycin

Staphylococcus haemolyticus is of increasing concern as a cause of several biofilm-associated infections, and today, it represents the second most common organism among clinical isolates of coagulase-negative staphylococci. However, little is known regarding the treatment of infections caused by these bacteria. In this study, we characterize the biofilm formed by S. haemolyticus strains isolated from bloodstream infections and assess in vitro the activity of rifampicin combined with daptomycin or tigecycline against bacteria growing in a biofilm. The results of our studies indicated that the majority (78 %) of methicillin-resistant Staphylococcus haemolyticus strains have the ability to form a biofilm in vitro. None of these strains carried icaADBC genes indicating that they form biofilm via ica-independent mechanisms. The molecular characterization of the biofilm showed that proteins are the predominant matrix component and play a major role in biofilm structure. Extracellular DNA and polysaccharides, other than polysaccharide intercellular adhesin, are also present in the biofilm matrix, but they play a minor role. The images obtained by confocal laser scanning microscopy showed that most S. haemolyticus strains formed a dense biofilm with a low number of dead cells. In vitro study demonstrated excellent activity of tigecycline in combination with rifampicin against cell growth in the proteinous biofilm. The BIC (biofilm inhibitory concentration) value for tigecycline/rifampicin ranged from 0.062 to 1 µg/ml, whereas for daptomycin/rifampicin from 0.125 to 2 µg/ml. These results indicated that the tigecycline/rifampicin combination was more effective against ica-independent biofilm, formed by S. haemolyticus strains, than the daptomycin/rifampicin combination.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus haemolyticus; Tigecycline

The prevalence of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) strains has become a serious problem worldwide. The aim of this study was to investigate the annual transitions of MRSA strains with the CA-MRSA feature, which were identified as SCCmec type IV or V, in a hospital setting in Japan. Between 2005 and 2012, MRSA strains were collected from a tertiary-care hospital in Tokyo, Japan, and SCCmec typing, detection of the virulence factors and antimicrobial susceptibility testing were conducted. The rate of detection of type II SCCmec, which is found mainly in healthcare-associated MRSA, significantly decreased from 90.0 (2005-2006) to 74.3 % (2011-2012) (P < 0.01). In contrast, the rate of detection of type IV SCCmec, which is mainly found in CA-MRSA, significantly increased from 5.8 (2005-2006) to 16.3 % (2011-2012) (P < 0.01). The rate of detection of the toxic shock syndrome toxin-1 gene significantly decreased from 66.7 (2005-2006) to 51.6 % (2011-2012) (P < 0.01), whilst that of the Panton-Valentine leukocidin gene significantly increased from 0.1 (2005-2006) to 2.1 % (2011-2012) (P < 0.01). The resistance rates of cefotaxime, levofloxacin, clarithromycin and minocycline decreased every year. The resistance rates of these antimicrobial agents for the SCCmec type IV or V strains were significantly lower than those for the SCCmec type I or II strains (P < 0.01, respectively). Therefore, these results suggest that the annual transitions of the virulence factors and antibiograms in MRSA are closely related to the increase of SCCmec type IV/V strains.

Topics: Bacterial Toxins; Bacterial Typing Techniques; Cefotaxime; Chromosomes, Bacterial; Clarithromycin; Community-Acquired Infections; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Enterotoxins; Exotoxins; Humans; Interspersed Repetitive Sequences; Japan; Leukocidins; Levofloxacin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Superantigens; Tertiary Care Centers; Virulence Factors

Bacterial infection of subcutaneous "pockets" housing cardiovascular implantable electronic devices is a significant clinical complication. In this study, pacemakers encapsulated in a blood plasma-based material (PBM) composited with antibiotics were investigated for use as prophylactics against such infections. PBMs, which are made from pooled allogeneic plasma and platelets, are off-the-shelf biomaterials that can be manufactured in the form of complex 3D shapes, extrudable putties, or injectable pastes. In vitro studies with PBM pastes formulated with rifampicin and minocycline demonstrated antibiotic release over 6 days, activity against Escherichia coli, and reduced cytotoxic effects of the antibiotics on fibroblasts. The materials were also evaluated in vivo in a rabbit model in which pacemaker pockets were inoculated with methicillin-resistant Staphylococcus aureus (S. aureus) strain and examined 1 week later. The pockets containing the pacemaker plus S. aureus were grossly purulent and culture positive, whereas pockets into which PBM with antibiotics were injected around the pacemaker were free of purulence and culture negative (p < 0.001). None of the pockets into which PBM without antibiotics were placed demonstrated purulence, but 60% were culture positive. These results demonstrate the potential of PBMs to deliver antibiotics to diminish the incidence of pocket infections for pacemakers and other implantable devices.

Topics: Animals; Anti-Bacterial Agents; Biocompatible Materials; Drug Carriers; Drug Delivery Systems; Escherichia coli; Escherichia coli Infections; Methicillin-Resistant Staphylococcus aureus; Minocycline; Pacemaker, Artificial; Plasma; Prostheses and Implants; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

In over a decade (2002 to 2012) of Staphylococcus aureus surveillance testing on 62,195 isolates, dalbavancin was demonstrated to be active against isolates that were either susceptible or nonsusceptible to daptomycin, linezolid, or tigecycline. Nearly all (99.8%) multidrug-resistant methicillin-resistant S. aureus isolates were inhibited by dalbavancin at ≤0.12 μg/ml (MIC50/90, 0.06/0.06 μg/ml), the current U.S. Food and Drug Administration (U.S. FDA) breakpoint. Overall, only 0.35% of the monitored S. aureus isolates had a dalbavancin MIC of either 0.25 or 0.5 μg/ml (i.e., were nonsusceptible).

Topics: Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Teicoplanin; Tigecycline; United States

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

Today, the most common cause of bloodstream infections, which led to high mortality, prolonged hospitalization and increased costs are the intravenous catheters. Among the microorganisms associated with catheter infections, staphylococci took the first place and because of their biofilm-forming properties they cause serious problems in treatment and management of the patients. Although the drug of choice in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection is vancomycin, its effect on the bacterial biofilm is known to be low. Tigecycline, newly used in our country is a well tolerated glycylcycline antibiotic. In this study, we aimed to compare the efficacy of tigecycline and vancomycin in an in vitro MRSA biofilm model. The study consisted of 10 MRSA strains, which were detected as causative agents of catheter-related infections in our hospital. The methicillin resistance of the strains were performed by disk diffusion test with oxacillin (1 μg) disks and the biofilm forming capacity of the strains was evaluated using the Congo red agar method. The silicone disks with created biofilm layer were exposed to tigecycline (2 mg/ml) and vancomycin (2 mg/ml) for 24 hours and for 5 days 4-hours per day in a model of antibiotic lock therapy. The present study showed that, after incubating the silicon discs in antibiotic solution for 24 hours, colony forming unit counts of MRSA decreased from 10(5) cfu/ml to 510 cfu/ml in the tigecycline group and from 105 cfu/ml to 3.800 cfu/ml in the vancomycin group and remained the same in the control (10(5) cfu/ml) group (p< 0.001). In the antibiotic lock therapy model, incubation with antibiotics for 4 hours per day, yielded that the average growth was 1.800 cfu/ml in the tigecycline group and 8.700 cfu/ml in the vancomycin group, which was statistically significant (p< 0.001). No growth was detected in the tigecycline group (0 cfu/ml) while in vancomycin group number of colonies in second, thirth and fourth days were 2.000, 260, 80 cfu/ml, respectively, no growth was seen in the fifth day. From the first day until the fourth day tigecycline was statistically more effective than vancomycin (p< 0.001, p< 0.001, p< 0.001, p= 0.013, according to days respectively). As a result, it was determined that tigecycline showed a higher effect on MRSA biofilm layer created on silicon discs and the results suggested that tigecycline might be a good alternative in the treatment of catheter infections.

Topics: Anti-Bacterial Agents; Biofilms; Catheter-Related Infections; Coloring Agents; Congo Red; Disk Diffusion Antimicrobial Tests; Humans; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxacillin; Staphylococcal Infections; Tigecycline; Vancomycin

We report the molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA) with resistance to tigecycline and to daptomycin isolated from intensive-care-unit patients in Brazil over a 6-month period. Thirty-six isolates (25 from infection sites, 11 from nasal sites) recovered from 23 patients who presented with MRSA infection during this period were characterized by pulsed-field gel electrophoresis, multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec) typing, and antimicrobial susceptibility profiling. Ten isolates from six patients and two isolates from different patients were resistant to tigecycline and daptomycin, respectively. Eight pulsotypes were identified and one, type A, accounted for 21 isolates from 12 patients; type A isolates were SCCmecII as were a further nine isolates of other pulsotypes. All but four of the total isolates were sequence type (ST) 5 or ST105 and classified as clonal complex (CC) 5; the historically prevalent lineage in Brazil, ST239-SCCmecIII, was identified in only three patients. Tigecycline-resistant strains were all ST105-SCCmecII and two patients were nasally colonized by strains of the same pulsotype found in infection sites. Two ST5-SCCmecII were daptomycin resistant after 48 h incubation. The origin and mechanism of these resistant strains remains unknown and further studies are warranted to determine whether such clones are becoming endemic in Brazilian hospitals and to assess their impact on infection control practice.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; Brazil; Daptomycin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Intensive Care Units; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Penicillin-Binding Proteins; Staphylococcal Infections; Tigecycline

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients in the United States is approximately 25%. Little is known about the relative proportion of hospital- versus community-associated strains or the antimicrobial susceptibility of MRSA in different CF centers. We hypothesized that the majority of MRSA isolates obtained from children with CF are those endemic in the hospital and that those associated with community acquisition (SCCmec IV) would be more resistant than typically seen in non-CF MRSA isolates.. We studied MRSA strains from seven pediatric CF centers to determine the clonal distribution based on DNA sequencing of the staphylococcal protein A gene (spa typing), the type of staphylococcal chromosomal cassette mec (SCCmec), and the proportion of strains with Panton-Valentine leukocidin (PVL). Antimicrobial susceptibility to systemic and topical antibiotics was compared between different MRSA types.. We analyzed 277 MRSA isolates from unique patients (mean age 11.15 ± 4.77 years, 55% male). Seventy % of isolates were SCCmec II PVL negative and the remainder SCCmec IV. Overall 17% MRSA strains were PVL positive (all SCCmec IV). Spa typing of 118 isolates showed most of the SCCmec II strains being t002, while SCCmec IV PVL positive isolates were t008, and SCCmec IV PVL negative isolates represented a variety of spa-types. The proportions of SCCmec II strains and spa-types were similar among centers. Overall rates of resistance to trimethoprim-sulfamethoxazole (4%), tetracycline (7%), tigecycline (0.4%), linezolid (0.4%) as well as fosfomycin (0.4%), fusidic acid (3%), and mupirocin (1%) were low. No strains were resistant to vancomycin. SCCmec II strains had higher rates of resistance to ciprofloxacin and clindamycin (P < 0.001) than SCCmec IV strains.. In this U.S. study, most MRSA isolates in the pediatric CF population were SCCmec II PVL negative. Rates of resistance were low, including to older and orally available antibiotics such as trimethoprim-sulfamethoxazole.

Topics: Acetamides; Adolescent; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; Bronchoscopy; Child; Child, Preschool; Cohort Studies; Cystic Fibrosis; DNA, Bacterial; Exotoxins; Female; Fosfomycin; Fusidic Acid; Humans; Leukocidins; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Molecular Typing; Mupirocin; Oxazolidinones; Penicillin-Binding Proteins; Pharynx; Pneumonia, Staphylococcal; Sequence Analysis, DNA; Sputum; Staphylococcal Infections; Staphylococcal Protein A; Tetracycline; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; United States

The aim of the present study was to compare the potential of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) targets against methicillin-resistant Staphylococcus aureus isolates collected from intensive care unit (ICU) settings. Monte Carlo simulations were carried out to simulate the PK/PD indices of the investigated antimicrobials. The probability of target attainment (PTA) was estimated at minimum inhibitory concentration values ranging from 0.03 to 32 μg/mL to define the PK/PD susceptibility breakpoints. The cumulative fraction of response (CFR) was computed using minimum inhibitory concentration data from the Canadian National Intensive Care Unit study. Analysis of the simulation results suggested the breakpoints of 4 μg/mL for ceftobiprole (500 mg/2 h t.i.d.), 0.25 μg/mL for dalbavancin (1000 mg), 0.12 μg/mL for daptomycin (4 mg/kg q.d. and 6 mg/kg q.d.) and tigecycline (50 mg b.i.d.), and 2 μg/mL for linezolid (600 mg b.i.d.) and vancomycin (1 g b.i.d. and 1.5 g b.i.d.). The estimated CFR were 100, 100, 70.6, 88.8, 96.5, 82.4, 89.4, and 98.3% for ceftobiprole, dalbavancin, daptomycin (4 mg/kg/day), daptomycin (6 mg/kg/day), linezolid, tigecycline, vancomycin (1 g b.i.d.) and vancomycin (1.5 g b.i.d.), respectively. In conclusion, ceftobiprole and dalbavancin have the highest probability of achieving their requisite PK/PD targets against methicillin-resistant Staphylococcus aureus isolated from ICU settings. The susceptibility predictions suggested a reduction of the vancomycin breakpoint to 1 μg/mL.

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; Computer Simulation; Cross Infection; Daptomycin; Dose-Response Relationship, Drug; Humans; Intensive Care Units; Linezolid; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Minocycline; Models, Biological; Monte Carlo Method; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Vancomycin

Staphylococcus epidermidis is a commensal inhabitant of the healthy human skin, but in the recent years, it has been recognized as a nosocomial pathogen especially in immunocompromised patients. The pathogenesis of S. epidermidis is thought to be based on its capacity to form biofilms on the surface of medical devices, where bacterial cells may persist, protected from host defence and antimicrobial agents. Rifampin has been shown to be one of the most active antimicrobial agents in the eradication of the staphylococcal biofilm. However, this antibiotic should not be used in monotherapy. Therefore, one of the objectives of our research was to study the efficacy of the tigecycline/rifampin combination against methicillin-resistant S. epidermidis embedded in biofilms. Of the 80 clinically significant S. epidermidis isolates, 75 strains possess the ability to form a biofilm. These bacteria formed the biofilm via ica-dependent mechanisms. However, other biofilm-associated genes, including aap (encoding accumulation-associated protein) and bhp (coding cell wall-associated protein), were present in 85 and 29 % of isolates, respectively. The biofilm structures of S. epidermidis strains were also analyzed in confocal laser scanning microscopy (CLSM) and the obtained image demonstrated differences in their architecture. In vitro studies showed that the MIC value for tigecycline against S. epidermidis growing in the biofilm ranged from 0.125 to 2 μg/mL. Tigecycline in combination with rifampin demonstrated higher activity against bacteria embedded in biofilms than tigecycline alone.

Topics: Anti-Infective Agents; Biofilms; DNA, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Microscopy, Confocal; Minocycline; Polymerase Chain Reaction; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline

Given increasing resistance, therapeutic options to treat MRSA soft tissue infections should be evaluated. This pooled analysis evaluated data from subjects enrolled in 6 tigecycline clinical trials with documented MRSA complicated skin and skin structure infections or diabetic foot infections (DFIs). Baseline characteristics were compared between subjects with and without molecularly classified community-acquired (CA) MRSA, specifically staphylococcal cassette chromosome mec (SCCmec) IV. Clinical response was compared by CA-MRSA designation and treatment group. A total of 378 subjects with MRSA soft tissue infections were identified, including 79 with DFI. A total of 249 (65.9%) were molecularly classified as CA-MRSA. Clinical response rates for MRSA soft tissue infection were similar between tigecycline and vancomycin (treatment difference, 1.0%; 95% confidence interval: -9.3, 12.0) as well as by infection type, SCCmec, and Panton-Valentine leukocidin (PVL) status. Tigecycline demonstrated comparable efficacy for treatment of MRSA soft tissue infections regardless of infection type, SCCmec, or PVL status.

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Trials as Topic; Diabetic Foot; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Molecular Typing; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Tigecycline; Treatment Outcome

Most drug delivery systems as treatment modalities for osteomyelitis have not been evaluated for resistant infections. Tigecycline (TG) is an antimicrobial agent that could be used in the treatment of multi-drug-resistant orthopedic infections. The objective of this in vitro study has been to determine what dosage of TG causes changes in the morphology and number of osteoblasts. We have also investigated whether nanoparticulate tigecycline-loaded calcium-phosphate/poly-DL-lactide-co-glycolide is biocompatible and whether it could release bioactive TG in a controlled manner during the observation time. The cytotoxicity was tested by analyzing the release of lactate dehydrogenase from dead osteoblasts to the medium. Staphylococcus aureus was used to verify the antibacterial effect of the multifunctional drug delivery system. At concentrations as achieved by local application, TG caused high toxic effect and impaired the normal osteoblastic morphology. The nanoparticulate multifunctional drug delivery system showed good compatibility and antibacterial effect during the observation time and thus appears to be suitable for the treatment of osteomyelitis caused by multi-drug-resistant microbes.

Topics: 3T3 Cells; Animals; Anti-Bacterial Agents; Calcium Phosphates; Cell Survival; Delayed-Action Preparations; Humans; Mice; Minocycline; Nanostructures; Osteoblasts; Polyglactin 910; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

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

The in vitro activities of tedizolid and 10 antistaphylococcal agents were compared against 111 methicillin-resistant Staphylococcus aureus (MRSA) strains from 14 epidemiologically characterized groups. Tedizolid, tigecycline, and daptomycin were the most potent agents, with tedizolid 4-fold more potent than linezolid. Tedizolid, linezolid, and vancomycin were unaffected by epidemiological types. Tigecycline and daptomycin had reduced potency against ST80-MRSA-IV and ST239-MRSA-III, respectively. Overall, tedizolid was highly potent against all MRSA strain types, including those resistant to other classes of drugs.

Topics: Anti-Bacterial Agents; Daptomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Organophosphates; Oxazoles; Staphylococcal Infections; Tigecycline

We present herein, a comparative study assessing the bactericidal kinetics of tigecycline, doxycycline, cefazolin and vancomycin against several methicllin-susceptible (MSSA) and -resistant (MRSA) Staphylococcus aureus isolates recovered from patients of 24 different cities in Argentina.. After genotypic characterization, 20 strains (10 MRSA and 10 MSSA) were selected for time-kill studies.. Vancomycin showed bactericidal effect (i.e. ≥3-log(10) CFU/mL decrease) against 50% and 10% of the MRSA strains at 4 x Minimal Inhibitory Concentration (MIC) and 2xMIC, respectively, after 24 h of incubation and displayed bactericidal activity against all MSSA isolates at 4xMIC. Cefazolin was bactericidal against 30% of MSSA strains at the higher concentration (4xMIC) and against 10% at 2 x MIC and MIC dose concentrations. The bactericidal magnitude of cefazolin observed after 24 h of incubation was lower than the vancomycin one. Albeit bacteriostactic, tigecycline at 2xMIC exerted a -1 to2-log decrease in the viable cell counts after 24-h incubation against 19 of the 20 S. aureus strains. Doxycycline was the least inhibitory of the antibiotics tested against both MRSA and MSSA, displaying no bactericidal activity in any of the cases and showing regrowth after 24 h of incubation at MIC level.. Vancomycin at high concentrations showed the best activity. Cefazolin did not show the activity expected for a beta-lactam antibiotic against MSSA. Tigecycline may be a useful option in infections caused by MRSA, where bactericidal activity is not an exclusive requirement and doxycycline does not seem an attractive alternative in serious infections.

Topics: Anti-Bacterial Agents; Argentina; Cefazolin; Doxycycline; Genotype; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin

In the fields of traumatology and orthopaedics staphylococci are the most frequently isolated pathogens. Staphylococcus aureus and Staphylococcus epidermidis are known to be the major causative agents of osteomyelitis. The increasing number of multiresistant Staphylococcus aureus and resistant coagulase-negative staphylococci as a trigger of complicated osteomyelitis and implant-associated infections is a major problem. Antibiotic therapy fails in 20% of cases. Therefore the development of novel antibiotics becomes necessary.. This study analyses tigecyclin, the first antibiotic of the glycylines, as a potential therapy for osteomyelitis caused by multiresistant Staphylococcus aureus. Therefore its intracellular activity and the potential use in polymethylmetacrylate-bone cement are examined. The intracellular activity of tigecyclin is determined by a human osteoblast infection model. The investigation of the biomechanical characteristics is conducted concerning the ISO 5833-guidelines.. Tigecyclin shows in vitro an intracellular activity that ranges between the antimicrobial activity of gentamicin and rifampicin. A significant negative effect on the biomechanical characteristics with an impaired stability is detected after adding tigecyclin to polymethylmetacrylate-bone cement with a percentage of 1.225% per weight.. This study shows that tigecyclin might be a potent alternative for the systemic therapy of osteomyelitis and implant-associated infections whereas the local application has to be reconsidered individually.

Topics: Anti-Bacterial Agents; Biomechanical Phenomena; Bone Cements; Cells, Cultured; Humans; Intracellular Space; Materials Testing; Minocycline; Models, Biological; Osteoblasts; Osteomyelitis; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

We examined the effects of tigecycline on three types of exoproteins, α-type phenol-soluble modulins (PSMα1 to PSMα4), α-hemolysin, and protein A, in 13 methicillin-resistant Staphylococcus aureus isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSMαs occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSMα1 to PSMα4, as protein A and α-hemolysin production was decreased under the same conditions by all of the antibiotics used.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Toxins; Clindamycin; Culture Media; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Protein Isoforms; Staphylococcal Infections; Tigecycline

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.

Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Biofilms; Disease Models, Animal; Male; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Oligopeptides; Polyethylene Terephthalates; Prosthesis-Related Infections; Protein Binding; Quorum Sensing; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

This study evaluated whether genotypically different clinical isolates of S. aureus have similar susceptibilities to individual antibiotics. It further aims to check the impact of biofilm on the in vitro activity of vancomycin, daptomycin, linezolid, and tigecycline against S. aureus clones. The study used a total of 60 different clinical MSSA and MRSA isolates. Susceptibilities were performed in planktonic cultures by macrobroth dilution and epsilon-test (E test) system. Biofilm production was determined using an adherent plate assay. The efficacy of antimicrobial activities against biofilms formation was checked using confocal laser scanning microscopy (CLSM). The study found that similar and different spa, MLST, and SCCmec types displayed high variation in their susceptibilities to antibiotics with tigecycline and daptomycin being the most effective. The biofilms were found resistant to high concentrations of most antibiotics tested with daptomycin being the most effective drug used in adhesive biofilms. A considerable difference exists among similar and various clone types against antibiotics tested. This variation could have contributed to the degree of virulence even within the same clonal genotype and enhanced heterogeneity in the infection potential. Thus, the development of a rapid and precise identification profile for each clone in human infections is important.

Topics: Acetamides; Anti-Infective Agents; Biofilms; Daptomycin; Genetic Variation; Genotype; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Viability; Minocycline; Oxazolidinones; Staphylococcal Infections; Tigecycline; Vancomycin

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an increasingly important cause of opportunistic infections in dogs and cats. Treatment options are often limited because of the high level of antimicrobial resistance. Doxycycline resistance is common, but variable mechanisms of doxycycline resistance exist, with some conferring resistance to doxycycline but not minocycline. However, there has been limited study of minocycline susceptibility in clinical MRSP isolates nor has the association of susceptibility and clonal complex been clearly established. The objective of this study was to evaluate the susceptibility of MRSP to tetracycline, doxycycline and minocycline, to determine the prevalence of tet(M) and tet(K) and to evaluate the impact of strain on minocycline susceptibility. One hundred seven MRSP isolates from dogs from Canada and the US were included; 79 from clinical infections and 28 from colonization sites. Thirty-nine (36%) isolates were susceptible to tetracycline, 41 (38%) to doxycycline and 70 (65%) to minocycline. Two main dru types, dt9a and dt11a, were present. When tetracycline or doxycycline resistant, dru type dt9a and related strains predominantly harboured tet(K) and were susceptible to minocycline. In contrast, dt11a and related strains tended to harbour tet(M), which confers resistance to all three tetracyclines. Minocycline might be a treatment option for some MRSP infections, even those that are doxycycline resistant; however, interpretive breakpoints may need to be re-assessed. Study of the pharmacokinetics and clinical efficacy of minocycline in dogs and cats is warranted.

Topics: Animals; Anti-Bacterial Agents; Canada; Cats; Dog Diseases; Dogs; Doxycycline; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus; Tetracycline; Tetracyclines

Topics: Adult; Aged; Anti-Bacterial Agents; Bone Diseases, Infectious; Drug Resistance, Multiple, Bacterial; Female; Humans; Joint Diseases; Male; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline; Treatment Outcome

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain MW2 harbors a plethora of toxins to mediate its virulence. However, toxin expression and regulation with simulated clinical antimicrobial exposures are unclear. This study evaluated these relationships using an in vitro pharmacodynamic hollow-fiber infection model. Clinical doses of clindamycin, linezolid, minocycline, trimethoprim-sulfamethoxazole (SXT), and vancomycin were simulated over 72 h against MW2 in the hollow fiber model. Expression levels of lukSF-PV and enterotoxin genes sec4, sek, seq, and sel2 were quantified by real-time PCR. Panton-Valentine leukocidin (PVL) was quantified by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was determined on polymorphonuclear cells (PMNs). Vancomycin produced the maximum MW2 killing (2.53 log(10) CFU/ml) after the first dose, but the greatest sustained killing over 72 h occurred with linezolid and clindamycin. Vancomycin and minocycline induced gene upregulation from 0 to 8 h, followed by downregulation for the remaining simulation period. Clindamycin decreased gene expression in the first 24 h, followed by moderate increases (2.5-fold) thereafter. Linezolid increased gene expression 11.4- to 200.4-fold but inhibited PVL production (0.6 ± 0.3 versus 5.9 ± 0.2 μg/ml, linezolid versus control at 72 h; P < 0.05). Similar effects on PVL production occurred with clindamycin and minocycline. SXT increased PVL production at 48 h (2.8-fold) and 72 h (4.9-fold) of treatment (P < 0.05), resulting in increased PVL cytotoxicity on PMNs. Linezolid, clindamycin, and minocycline were the most effective agents on decreasing the virulence potential in CA-MRSA, notably after 8 h of treatment. SXT had minimal effects on toxin gene regulation, but it increased production and cytotoxicity of PVL toxin in the model and may enhance virulence when it is used to treat severe infections.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; Cell Culture Techniques; Clindamycin; Community-Acquired Infections; Enzyme-Linked Immunosorbent Assay; Exotoxins; Gene Expression Regulation, Bacterial; Humans; Leukocidins; Leukocytes, Mononuclear; Linezolid; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Models, Biological; Oxazolidinones; Real-Time Polymerase Chain Reaction; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Virulence Factors

We investigated the in vivo efficacy of tigecycline, a new glycylcycline (a tetracycline derivative), in the management of methicillin-resistant Staphylococcus aureus (MRSA)-infected experimental surgical wounds in rats. The main outcome measures were quantitative bacterial culture, histological examination and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9) and collagen IV.. An animal model was used to compare the in vivo efficacy of teicoplanin and tigecycline in the treatment of burn wound infections by S. aureus. A copper bar, heated in boiling water, was placed on the paraspinal site of each rat, resulting in full thickness burns. A small gauze was placed over each burn and then inoculated with 5 × 10(7) cfu of S. aureus ATCC 43300. To mimic the clinical situation in burn patients, surgical debridement was performed 48 h after the injury. The wounds were left to heal by secondary intention. The study included an uninfected control group that did not receive any treatment, a contaminated group that did not receive any treatment, and two contaminated groups treated with intraperitoneal tigecycline (2 mg/kg) and teicoplanin (7 mg/kg), respectively.. All antibiotic treatments were significantly effective. Tigecycline showed the highest antimicrobial activity, with a better impact on histological results. Infected rats treated with tigecycline showed a significant decrease in MMP-9 expression both in epithelium and in dermis compared with rats treated with teicoplanin.. Tigecycline, besides its antimicrobial activity, exerts an important modulatory effect on MMP-9, accelerating wound healing in staphylococcal-infected burns.

Topics: Animals; Bacterial Load; Burns; Disease Models, Animal; Histocytochemistry; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Methicillin-Resistant Staphylococcus aureus; Minocycline; Rats; Rats, Wistar; Staphylococcal Infections; Teicoplanin; Tigecycline; Treatment Outcome; Wound Healing; Wound Infection

Central venous catheters are frequently used. The commonest cause of catheter-related bloodstream infections (CRBSI) is coagulase-negative staphylococci (CoNS) associated with adherent biofilm. Tigecycline, a derivative of tetracycline, acts against strains producing biofilm. In this study, we aimed to determine the effect of tigecycline in a CRBSI model. A single dose of 10(8) colony-forming units (CFU)/mL of slime-producing Staphylococcus epidermidis was given through polyethylene catheters inserted into 24 rabbits. After 72 h, groups of eight rabbits were treated with heparin, vancomycin/heparin or tigecycline/heparin. Blood obtained from peripheral veins and the catheter lumen as well as catheter tips were cultured, and three catheters from each group were studied using electron microscopy. Surfaces were randomly subdivided and areas with ≥50 bacteria were compared. Blood cultures were positive from all heparin-treated rabbits but were negative from those receiving either antibiotic (P<0.001). Catheter tip cultures revealed growth from six, two and one rabbit(s) given heparin, vancomycin and tigecycline, respectively. Electron microscopy showed that catheters from heparin-treated rabbits were most heavily colonised (more areas with ≥50 CFU) compared with catheters from animals treated with vancomycin or tigecycline (P<0.003 and P<0.001, respectively). In conclusion, this study shows that tigecycline and vancomycin are both effective for treating CRBSI due to CoNS. Electron microscopy of catheters themselves suggests that tigecycline is superior to vancomycin (P<0.001). Tigecycline may be useful for the treatment of CRBSI.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Blood; Catheter-Related Infections; Catheterization, Central Venous; Catheters; Culture Techniques; Disease Models, Animal; Female; Heparin; Humans; Microscopy, Electron, Scanning; Minocycline; Rabbits; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline; Time Factors; Vancomycin

To evaluate the usefulness of daptomycin, tigecycline, and linezolid for the treatment of MRSA infection compared with vancomycin in Belgium, the United Kingdom/Ireland, and Spain.. The methodology included the following steps: acquisition of microbiological and pharmacokinetic data, Monte Carlo simulation, estimation of the probability of target attainment (PTA), and calculation of the cumulative fraction of response (CFR).. We showed that differences in the susceptibility of MRSA strains among countries may justify differences in the antibiotic dose selection. Two, 3, and 4 g daily of vancomycin seem be adequate in Belgium, Spain, and United Kingdom/Ireland respectively. The CFR obtained with 50 mg tigecycline every 12 h was higher in Spain than in Belgium and the United Kingdom/Ireland, but with the highest dose (100 mg q12h) the CFR was always 100%. At least 8 mg/kg daptomycin is necessary in United Kingdom/Ireland, but 4 mg/kg may be sufficient in Spain, and probably in Belgium. Six hundred mg q12h linezolid may be adequate in the four countries.. Our study reinforces the idea that the local MIC distribution must be considered in order to increase the probability of success of empirical treatment and must be periodically updated.

Topics: Acetamides; Anti-Bacterial Agents; Belgium; Daptomycin; Ireland; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Spain; Staphylococcal Infections; Tigecycline; United Kingdom; Vancomycin

Vancomycin is widely used for intravenous prophylaxis against surgical implant infections. However, it is unclear whether alternative antibiotics used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections are effective as prophylactic agents. The aim of this study was to compare the efficacies of vancomycin, daptomycin, and tigecycline as prophylactic therapy against a methicillin-sensitive S. aureus (MSSA) or MRSA surgical implant infection in mice. MSSA or MRSA was inoculated into the knee joints of mice in the presence of a surgically placed medical-grade metallic implant. The efficacies of low- versus high-dose vancomycin (10 versus 110 mg/kg), daptomycin (1 versus 10 mg/kg), and tigecycline (1 versus 10 mg/kg) intravenous prophylaxis were compared using in vivo bioluminescence imaging, ex vivo bacterial counts, and biofilm formation. High-dose vancomycin, daptomycin, and tigecycline resulted in similar reductions in bacterial burden and biofilm formation. In contrast, low-dose daptomycin and tigecycline were more effective than low-dose vancomycin against the implant infection. In this mouse model of surgical implant MSSA or MRSA infection, daptomycin and tigecycline prophylaxis were effective over a broader dosage range than vancomycin. Future studies in humans will be required to determine whether these broader effective dose ranges for daptomycin and tigecycline in mice translate to improved efficacy in preventing surgical implant infections in clinical practice.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Colony Count, Microbial; Daptomycin; Drug Administration Schedule; Humans; Injections, Intravenous; Knee Prosthesis; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred C57BL; Minocycline; Models, Animal; Molecular Imaging; Prosthesis-Related Infections; Staphylococcal Infections; Tigecycline; Vancomycin

Daptomycin is licensed in adults for the management of Staphylococcus aureus methicillin-resistant infections, including bone and skin complicated infections. We describe for the first time its use in a renal transplant recipient for Fabry-Anderson Disease with right heel osteomyelitis. The patient was unresponsive to first-line Teicoplanin and second-line Tigecycline, whereas he was successfully treated with third-line Daptomycin monotherapy at 4 mg/Kg/qd for 4 weeks. Local debridement was performed in advance of each line of treatment.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Calcaneus; Daptomycin; Fabry Disease; Heel; Humans; Kidney Transplantation; Male; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Metronidazole; Minocycline; Osteomyelitis; Renal Insufficiency; Salvage Therapy; Staphylococcal Infections; Teicoplanin; Tigecycline; Tomography, X-Ray Computed

Perioperative infection of an aortic graft is one of the most devastating complications of vascular surgery, with a mortality rate of 10% to 30%. The rate of amputation of the lower limbs is generally >25%, depending on the graft material, the location of the graft and infection, and the bacterial virulence. In vitro studies suggest that an antibiotic-impregnated graft may help prevent perioperative graft infection. In a pilot animal study, we tested a locally developed technique of bonding Dacron aortic grafts with three antimicrobial agents to evaluate the ensuing synergistic preventive effect on direct perioperative bacterial contamination.. We surgically implanted a 6-mm vascular knitted Dacron graft in the infrarenal abdominal aorta of six Sinclair miniature pigs. Two pigs received unbonded, uninoculated grafts; two received unbonded, inoculated grafts; and two received inoculated grafts that were bonded with chlorhexidine, rifampin, and minocycline. Before implantation, the two bonded grafts and the two unbonded grafts were immersed for 15 minutes in a 2-mL bacterial solution containing 1 to 2 × 10(7) colony-forming units (CFU)/mL of Staphylococcus aureus (ATCC 29213). Two weeks after graft implantation, the pigs were euthanized, and the grafts were surgically excised for clinical, microbiologic, and histopathologic study.. The two bonded grafts treated with S aureus showed no bacterial growth upon explant, whereas the two unbonded grafts treated with S aureus had high bacterial counts (6.25 × 10(6) and 1.38 × 10(7) CFU/graft). The two control grafts (unbonded and untreated) showed bacterial growth (1.8 × 10(3) and 7.27 × 10(3) CFU/graft) that presumably reflected direct, accidental perioperative bacterial contamination; S cohnii ssp urealyticus and S chromogenes, but not S aureus, were isolated. The histopathologic and clinical data confirmed the microbiologic findings. Only pigs that received unbonded grafts showed histopathologic evidence of a perigraft abscess.. Our results suggest that bonding aortic grafts with this triple antimicrobial combination is a promising method of reducing graft infection resulting from direct postoperative bacterial contamination for at least 2 weeks. Further studies are needed to explore the ability of this novel graft to combat one of the most feared complications in vascular surgery.

Topics: Animals; Anti-Infective Agents; Aorta, Abdominal; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Chlorhexidine; Coated Materials, Biocompatible; Disease Models, Animal; Drug Therapy, Combination; Minocycline; Pilot Projects; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Swine; Swine, Miniature; Time Factors

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

The aim of this study was to determine whether vancomycin resistant Staphylococcus aureus (VRSA) and vancomycin intermediate susceptible S.aureus (VISA) strains were present among methicillin-resistant S.aureus (MRSA) strains isolated from patients hospitalised at intensive care units (ICU) of hospitals located at different regions of Turkey and to determine the minimum inhibitory concentration (MIC) values of teicoplanin, linezolid, tigecycline, quinupristin-dalfopristin and daptomycin, which are alternative drugs for the treatment of MRSA infections. A total of 260 MRSA clinical strains (isolated from 113 lower respiratory tract, 90 blood, 24 wound, 17 catheter, 13 nasal swabs, two urine and one CSF sample) were collected from nine health-care centers in eight provinces [Ankara (n= 52), Konya (n= 49), Antalya (n= 40), Istanbul (n= 7), Izmir (37), Diyarbakir (n= 15), Van (n= 12), Trabzon (n= 48)] selected as representatives of the seven different geographical regions of Turkey. Methicillin resistance was determined by cefoxitin disk diffusion in the hospitals where the strains were isolated and confirmed by oxacillin salt agar screening at the Refik Saydam National Public Health Agency. Screening for VISA and VRSA was conducted using the agar screening test and E-test. Susceptibility of the MRSA strains to other antibiotics was also determined by E-test method. None of the 260 MRSA strains were determined to be VRSA or VISA. All were susceptible to teicoplanin and linezolid, and susceptibility rates to daptomycin, tigecycline and quinupristin-dalfopristin were 99.6%, 96.9%, and 95%, respectively. Absence of VISA and VRSA among the MRSA strains surveyed currently seemed hopeful, however, continuous surveillance is necessary. In order to prevent the development of VISA and VRSA strains the use of linezolid, tigecycline, quinupristin-dalfopristin and daptomycin should be encouraged as alternative agents of treatment of MRSA infections.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Humans; Intensive Care Units; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Turkey; Vancomycin; Vancomycin Resistance; Virginiamycin

This study assessed the demographics, antimicrobial susceptibility, and molecular epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and health care-associated MRSA (HA-MRSA) in Canadian hospitals between 2007 and 2009. Among 3589 S. aureus, 889 (24.8%) were MRSA; 224 (25.2%) were CA-MRSA genotypes and 644 (72.4%) were HA-MRSA genotypes. The prevalence of CA-MRSA genotypes increased from 19.5% in 2007 to 31.9% in 2009 (P < .001). CMRSA10/USA300 (73.7%) was the predominant CA-MRSA epidemic type; the most common HA-MRSA epidemic type was CMRSA2/USA100/800 (83.5%). CA-MRSA genotypes carried SCCmec type IVa (98.2%) and were largely agr type I (73.2%). Most HA-MRSA genotypes were SCCmec type II (81.2%) and agr type II (83.4%). Panton-Valentine leukocidin was detected in 201/224 (89.7%) CA-MRSA genotypes and 3/644 (0.5%) HA-MRSA genotypes. An increase in vancomycin minimum inhibitory concentration (MIC) was observed in HA-MRSA genotypes overall, with 1.3% (4/305) of strains in 2007 and 4.6% (7/152) in 2009 exhibiting vancomycin MICs of 2 μg/mL. No MRSA resistance occurred with linezolid, daptomycin, or tigecycline. In conclusion, CA-MRSA genotypes represented 25.2% of all MRSA and continue to increase in prevalence in Canadian hospitals.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Toxins; Canada; Child; Child, Preschool; Community-Acquired Infections; Cross Infection; Daptomycin; DNA, Bacterial; Drug Resistance, Bacterial; Exotoxins; Female; Hospitals; Humans; Infant; Leukocidins; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Minocycline; Oxazolidinones; Staphylococcal Infections; Tigecycline; Vancomycin Resistance

The aim of this study was to compare the in vivo activities of the new antistaphylococcal drugs ceftaroline fosamil, daptomycin and tigecycline at projected human therapeutic doses against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains in a rabbit model of endocarditis.. The efficacy of therapeutic regimens in our model was evaluated following 4 days of treatment by determining colony counts of infected vegetations. Emergence of resistant variants during therapy was assessed.. Using this model of infective endocarditis, ceftaroline fosamil and daptomycin demonstrated high bactericidal in vivo activity (reduction of >5 log(10) cfu/g of vegetation) after a 4 day treatment against MSSA, MRSA and GISA strains. Both drugs were more efficacious than tigecycline, which showed moderate activity but failed to exhibit a bactericidal effect. Ceftaroline was superior to daptomycin in terms of sterilization of the vegetations. Emergence of resistant variants during daptomycin therapy was observed in two animals (one in the MSSA group and one in the MRSA group) but was not observed in ceftaroline- or tigecycline-treated animals.. The novel β-lactam agent ceftaroline fosamil was the most active bactericidal drug in this model and is a promising therapeutic option for the treatment of severe S. aureus infections, including those caused by MRSA and GISA strains.

Topics: Animals; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Colony Count, Microbial; Daptomycin; Disease Models, Animal; Drug Resistance, Bacterial; Endocarditis, Bacterial; Female; Methicillin-Resistant Staphylococcus aureus; Microbial Viability; Minocycline; Rabbits; Rodent Diseases; Staphylococcal Infections; 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

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin resistant Staphylococcus aureus (MRSA) are important nosocomial pathogens. This study reports the in vitro activity of tigecycline against 573 and 482 ESBL-producing Enterobacteriaceae and MRSA isolates, respectively. More than 94% of all tested isolates were susceptible to tigecycline; MIC(90) found was 0.25 to 2 mg/L for ESBL-producing Enterobacteriaceae and was 0.125 mg/L for MRSA. Tigecycline demonstrated excellent in vitro activity against a wide spectrum of nosocomial pathogens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mexico; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Tigecycline; Young Adult

Tigecycline appears as an alternative therapy against methicillin-resistant Staphylococcus aureus (MRSA) with limited clinical experience. We evaluate the efficacy of tigecycline and its combination with rifampin in comparison to that for vancomycin in a rat model of foreign-body infection by MRSA.. A tissue-cage infection model were used; therapy with tigecycline, vancomycin, rifampin, tigecycline plus rifampin and vancomycin plus rifampin was administered intraperitoneally for 7 days. The antibiotic efficacy was evaluated in the tissue-cage fluid and in the coverslips (attached bacteria); the emergence of resistance was screened.. Among monotherapies rifampin was the best treatment (decrease in log CFU/ml of tissue-cage fluid, 2.75) (P < 0.05). The addition of rifampin improved the efficacy of vancomycin (decrease, 2.28) and tigecycline (decrease, 1.56) in solitary; there were not significantly differences between tigecycline-rifampin (decrease, 3.39) and vancomycin-rifampin (decrease, 3.70), but only the latter was better than rifampin alone (P < 0.05). Resistant strains were only detected using rifampin alone.. tigecycline alone was the least effective treatment. Tigecycline-rifampin prevented the emergence of rifampin resistance, thus allowing the benefits of rifampin over time against staphylococcal foreign-body infections, but its efficacy needs to be evaluated in comparison with other anti-MRSA combined therapies.

Topics: Animals; Anti-Bacterial Agents; Diffusion Chambers, Culture; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Foreign Bodies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Models, Animal; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tigecycline; Time Factors; Treatment Outcome; Vancomycin

This study aimed to evaluate the in vitro activity of minocycline combined with fosfomycin against isolates of methicillin-resistant Staphylococcus aureus (MRSA). A total of 87 clinical isolates of MRSA collected from three Chinese hospitals were included in the study. The checkerboard method with determination of the fractional IC index (FICI) was used to determine whether antibiotic combinations act synergistically against these isolates. The susceptibility results for minocycline and fosfomycin were interpreted according to the most relevant criteria. The results demonstrated the following interactions: 76 isolates (87.4%) showed synergistic interactions (FICI0.5) and 11 isolates (12.6%) showed indifferent interactions (0.5

Topics: Anti-Bacterial Agents; China; Drug Interactions; Fosfomycin; Hospitals; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections

Topics: Anti-Infective Agents, Local; Conjunctivitis, Bacterial; Eye Infections, Bacterial; Female; Humans; Infant, Newborn; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Ointments; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Cerebral Ventriculitis; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Drainage; Female; Humans; Hydrocephalus; Male; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Osteomyelitis; Oxazolidinones; Staphylococcal Infections; Tigecycline; Vancomycin

A relevant bacterial load in cutaneous wounds significantly interferes with the normal process of healing. Vitamin E (VE) is a known immunomodulator and immune enhancer. Here, it was shown that administration of VE before infection was effective at increasing the antimicrobial activity of daptomycin (DAP) or tigecycline (TIG) in a mouse model of wound infection caused by meticillin-resistant Staphylococcus aureus (MRSA). A wound was established through the panniculus carnosus of mice and inoculated with MRSA. Mice were assigned to six groups: a VE pre-treated group with no antibiotics given after MRSA challenge; two VE pre-treated groups with DAP or TIG given after MRSA challenge; two groups treated with DAP or TIG only after MRSA challenge; and a control group that did not receive any treatment. Mice receiving each antibiotic alone showed a 3 log decrease in the number of c.f.u. recovered compared with the control group, mice treated with VE plus TIG had a 4 log decrease, whilst mice treated with VE plus DAP had the largest decrease in c.f.u. recovered (5 logs). The increased antimicrobial effect seen from treatment with VE plus antibiotics was associated with increased levels of natural killer cell cytotoxicity, with a more pronounced increase in leukocyte populations in mice treated with VE plus DAP. These data suggest that treatment with VE prior to infection and subsequent antibiotic treatment act in synergy.

Topics: Animals; Anti-Bacterial Agents; Daptomycin; Drug Synergism; Drug Therapy, Combination; Immunomodulation; Killer Cells, Natural; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tigecycline; Vitamin E; Wound Infection

We report the antibiotic treatments administered to a female dog with mastitis and successive pyoderma. Microbiological investigations allowed the identification of Staphylococcus pseudintermedius after 54 days of various antibiotic treatments. The isolate carried the mecA gene and was resistant to 9 of 15 tested antibiotics. Consistent antibiotic treatment of the infection was possible only after accurate microbiological diagnosis.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; Dog Diseases; Dogs; Drug Eruptions; Female; Mastitis; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staphylococcal Infections; Staphylococcus

Tigecycline achieves high intracellular concentrations in polymorphonuclear leukocytes (PMNs). To evaluate the effects of tigecycline on human PMNs, PMNs were incubated with tigecycline dilutions (0.1 to 100 mg L-1). Phagocytosis-associated PMN Fcγ- and complement receptors as well as phagocytosis and oxidative burst induced by Staphylococcus aureus were measured by flow cytometry. Incubation with tigecycline caused small but significant decreases in the density of complement receptors CD11b and CD35 (all concentrations) and Fcγ receptors CD16 and CD32 (high concentrations), but not in the percentages of receptor-bearing cells, except for small reductions in the proportions of CD16 positive cells at high concentrations. Tigecycline had no effect on phagocytosis or oxidative burst induced by S. aureus. Tigecycline was thus associated with decreased density of PMN complement and (at high concentrations) Fcγ receptors. Although statistically significant, the differences were small and did not influence the PMN function as measured by phagocytosis and oxidative burst.

Topics: Animals; Anti-Bacterial Agents; Antibodies, Monoclonal, Murine-Derived; CD11b Antigen; Dose-Response Relationship, Drug; Humans; Mice; Minocycline; Neutrophils; Phagocytosis; Receptors, Complement 3b; Receptors, IgG; Respiratory Burst; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines; Tigecycline

The aim of this study was to determine the minimal inhibitory concentration (MIC) values of vancomycin, teicoplanin, tigecycline and linezolid in 100 methicillin-resistant staphylococci [21 methicillin-resistant Staphylococcus aureus (MRSA) and 79 methicillin-resistant coagulase negative staphylococcus (MR-CNS)] isolated as agents of nosocomial infection from patients at Ankara Training and Research Hospital between June 2005-March 2007. The MIC values for vancomycin, teicoplanin, linezolid and tigecycline were tested by E-test method (AB Biodisk, Sweden). For 21 MRSA strains MIC50 and MIC90 values were as follows: vancomycin 0.125 µg/ml and 1 µg/ml; teicoplanin 0.5 µg/ml and 3 µg/ml, linezolid 0.047 µg/ml and 0.19 µg/ml; tigecycline 0.094 µg/ml and 0.5 µg/ml, respectively. For 79 MR-CNS strains MIC50 and MIC90 values were as follows: vancomycin 0.5 µg/ml and 2 µg/ml; teicoplanin 2 µg/ml and 4 µg/ml; linezolid 0.125 µg/ml and 0.25 µg/ml; tigecycline 0.38 µg/ml and 0.5 µg/ml, respectively. No resistance to vancomycin, teicoplanin, tigecycline and linezolid were determined in methicillin-resistant staphylococcus strains isolated from the inpatients in our hospital. Among glycopeptides, MIC50 and MIC90 values of vancomycin were found to be lower than that of teicoplanin.

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Turkey; Vancomycin

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Colony Count, Microbial; Dose-Response Relationship, Drug; False Negative Reactions; Humans; Minocycline; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

Treatment of ventriculoperitoneal shunt infections frequently requires placement of an external ventricular drain (EVD). Surveillance specimens obtained from antibiotic-impregnated (AI) EVDs may be less likely to demonstrate bacterial growth, potentially resulting in undertreatment of an infection. The purpose of this study was to assess whether AI EVDs had any significant effect on bacterial culture results compared with nonantibiotic-impregnated (NAI) EVDs.. In vitro assays were performed using AI EVDs containing minocycline and rifampin (VentriClear II, Medtronic) and NAI EVD controls (Bioglide, Medtronic). The presence of antibiotics was evaluated via capillary electrophoresis of sterile saline drawn from AI and NAI EVDs after predefined incubation intervals. Antimicrobial activity was assessed by evaluating zones of inhibition created by the catheter aspirates on plates inoculated with a quality control strain of Staphylococcus epidermidis (American Type Culture Collection strain 12228). To determine the effects of cultures drawn through AI compared with NAI EVDs, the quality control strain was then incubated within 4 new AI and 4 new NAI EVDs for predefined intervals before being plated on culture media. Spread and streak plate culture results from each type of catheter were compared at each time interval.. Capillary electrophoresis showed that more minocycline than rifampin was eluted from the AI EVDs. Sterile saline samples incubated within the AI EVDs demonstrated zones of growth inhibition when placed on plates of S. epidermidis at all time intervals tested. No zones of inhibition were noted on NAI EVD control plates. When a standardized inoculum of S. epidermidis was drawn through AI and NAI EVDs, antimicrobial effects were observed after incubation in the AI EVD group only. Colony counting demonstrated that significantly fewer colonies resulted from samples drawn through AI compared with NAI EVDs at the multiple time intervals. Similarly, streak plating yielded a statistically significant number of false-negative results from AI compared with NAI EVDs at 2 time intervals.. The findings in the current study indicate that the risk of a false-negative culture result may be increased when a CSF sample is drawn through an AI catheter. In the management of a known shunt infection, a false-negative result from an EVD culture specimen may lead to an inappropriately short duration of antibiotic therapy. These data have significant clinical implications, particularly given the widespread use of AI drains and the current high rates of shunt reinfection after EVD use worldwide.

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Colony Count, Microbial; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

For Francis Tally, both medicine and science were highly personal undertakings. Tally thought that emotional engagement was important in one's work and one's life, which were inseparable in his case. Indeed, Tally materially participated in no fewer than 4 programs that resulted in the approval and commercialization of novel antibiotics. These included piperacillin-tazobactam (which is currently the injectable antibiotic with the largest volume of sales worldwide) and daptomycin. This article focuses on the discovery and development of tigecycline.

Topics: Anti-Bacterial Agents; Drug Approval; Drug Design; Drug Industry; Drug Resistance, Multiple, Bacterial; History, 20th Century; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tigecycline

Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Respiratory System; Staphylococcal Infections; Tigecycline

The in vitro activity of tigecycline was determined using a well-defined collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 202), including 33 livestock-associated strains. Susceptibility testing was performed using the Etest system. Among the 202 MRSA strains, three (1.5%) had a minimum inhibitory concentration (MIC) value for tigecycline greater than 0.5 mg/l, which are considered to be resistant. When these strains were tested using Iso-Sensitest medium, the MICs were substantially lower and no resistance was found. This discrepancy warrants further investigations into the preferred test conditions for tigecycline. In conclusion, tigecycline showed good activity against MRSA strains in vitro.

Topics: Animals; Animals, Domestic; Anti-Bacterial Agents; Humans; Linear Models; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tigecycline

Topics: Anti-Bacterial Agents; Doxycycline; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Treatment Outcome

The use of policies and practices regarding surveillance, decolonization, and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and the formulary status of various antimicrobial agents used to treat MRSA were characterized.. A 61-item questionnaire was sent to the director of pharmacy at each of 263 acute care hospitals that were members of a national group purchasing organization.. Responses were received from 102 hospitals (38.8%). Active surveillance culture protocols were in place at 44 hospitals (44%). Nearly 75% engaged in key antimicrobial stewardship activities, while only 18% reported having a formal antimicrobial stewardship team. MRSA decolonization policies existed in approximately 25% of the respondent hospitals. Vancomycin was on the formulary in all hospitals with few restriction policies, while the newer anti-MRSA agents-linezolid, daptomycin, and tigecycline-were on the formulary in most hospitals but with restrictions. Vancomycin was the most commonly used antimicrobial for the treatment of various MRSA infections, followed by linezolid. Nearly 70% of the respondent hospitals reported having a vancomycinspecific dosing or monitoring guideline in place. Most specified the use of actual body weight for dosing and trough serum concentrations at steady state for therapeutic monitoring (84% and 91%, respectively). Most guidelines did not address the use of a loading dose to attain a high target trough or methods for choosing alternative agents.. Acute care hospitals in the United States varied in their policies and practices of surveillance, decolonization, and treatment of MRSA infections, but most were consistent with national guideline recommendations.

Topics: Acetamides; Anti-Bacterial Agents; Clinical Protocols; Daptomycin; Formularies, Hospital as Topic; Guidelines as Topic; Health Care Surveys; Hospitals; Humans; Infection Control; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Organizational Policy; Oxazolidinones; Patient Isolation; Pharmacy Service, Hospital; Staphylococcal Infections; Surveys and Questionnaires; Tigecycline; Vancomycin

The purpose of our study was to evaluate the anti-staphylococcal biofilm activity of tigecycline, compared with a group of recently developed or commonly used antimicrobials such as linezolid, daptomycin, levofloxacin, tobramycin and rifampin, all possessing putative antibiofilm properties, on a sample of multi-drug-resistant methicillin-resistant Staphylococcus aureus grown as a planktonic and mature biofilm. We determined conventional minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for the planktonic forms, MICs of adherent cells and finally, minimum biofilm eradication concentrations (MBECs). No drug was able to inhibit adherent bacteria at the same concentration necessary for eradicating a mature biofilm; the latter concentrations varied from three to seven times higher than the ones inhibiting adhesion. The concentrations eradicating biofilm were reached by rifampin and daptomycin at lower concentrations with respect to the other antibiotics tested; tigecycline was able to inhibit mature biofilms at higher concentrations, while all the other antibiotics were only able to inhibit adhering cells.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Staphylococcal Infections; Tigecycline

We investigated the activity of tigecycline in combination with gentamicin for the treatment of biofilm-forming methicillin-resistant and sensitive Staphylococcus aureus in an in vitro pharmacodynamic model. Tigecycline monotherapy demonstrated bacteriostatic activity throughout 48 h (-0.24 +/- 0.17 log(10) CFU/mL), whereas tigecycline in combination with gentamicin demonstrated significant (P < 0.002) kill (-3.66 +/- 0.26 log(10) CFU/mL) at 48 h. The addition of gentamicin to tigecycline significantly improved the killing activity of tigecycline in biofilm-forming S. aureus.

Topics: Anti-Bacterial Agents; Biofilms; Culture Media; Drug Interactions; Drug Therapy, Combination; Gentamicins; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Models, Biological; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.. To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.. Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections.

Topics: Animals; Anti-Bacterial Agents; Arthroplasty; Disease Models, Animal; Humans; Joint Diseases; Joints; Male; Mice; Mice, Inbred C57BL; Minocycline; Postoperative Complications; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Device-related infections represent a significant clinical challenge. Once established, these infections prove difficult to treat with existing antibiotic regimens, compromising the health of device recipients, and usually requiring surgical intervention to resolve. The purpose of this study was to determine the ability of the AIGIS(RX)® Anti-Bacterial envelope to reduce the formation of bacterial biofilm on implanted pacing devices.. An infection was established in a rabbit model by creating bilateral subcutaneous implant pockets, into which a pacing device with or without AIGIS(RX)® was placed. The incisions were closed, and a defined dose of bacteria was infused into each implant pocket. After seven days, devices were explanted and assessed for viable bacteria by a sonication/vortex procedure to quantify bacteria, and by imaging of the device surface by scanning electron microscopy and laser scanning confocal microscopy.. The presence of the AIGIS(RX)® envelope eliminated recoverable, viable bacteria from the explanted devices using a vortex/sonication technique from in vivo models of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus capitis, and Escherichia coli infections. Scanning electron microscopy and confocal microscopy demonstrate greatly reduced biological material on the pacemaker surfaces in the presence of the AIGIS(RX)® envelope compared to untreated controls.. These results demonstrate that in this animal model, the AIGIS(RX)® device reduces the formation of adherent bacteria and reduces bioburden on implanted, infected pacemaker devices.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Disease Models, Animal; Drug Therapy, Combination; Equipment Contamination; Escherichia coli; Escherichia coli Infections; Microbial Viability; Microscopy, Confocal; Microscopy, Electron, Scanning; Minocycline; Pacemaker, Artificial; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus; Time Factors

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infections has created a need for additional antimicrobial options. Patients at the Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, who received alternative (nonvancomycin, nonlinezolid) therapy for MRSA infections from January 2004 to December 2005 were identified retrospectively, with sulfamethoxazole/trimethoprim, clindamycin, tetracyclines, and fluoroquinolones assessed as alternative agents. Medical records were reviewed to determine therapeutic outcome and drug tolerance. During 2004 to 2005, 87 subjects received alternative therapy for MRSA infections. Infections included skin/musculoskeletal (n=74 [85%]) and urinary tract infections (n=13 [15%]). Thirty-five (40%) subjects received vancomycin initially, and then an alternative agent, whereas 52 (60%) received only alternative therapy. Treatment succeeded clinically in 77 (89%; 95% confidence interval, 78-96%) subjects. Adverse events were uncommon (6 subjects) and minor, necessitating a change of therapy in only 4 subjects. Alternative agents can be used successfully to treat non-life-threatening MRSA infections in appropriate patients. Randomized comparative trials are needed.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Doxycycline; Drug Resistance, Bacterial; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Multivariate Analysis; Regression Analysis; Retrospective Studies; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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

Tigecycline is a currently marketed antimicrobial agent with activity against resistant gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA). Despite the proven efficacy of tigecycline in the treatment of infections caused by these pathogens, questions remain as to the exposure-response relationship best associated with its efficacy. The purpose of this study was to define this relationship against seven distinct S. aureus isolates by using a neutropenic murine thigh model. Single-dose pharmacokinetics were evaluated, and free drug exposures were calculated after determination of protein binding. Doses of 1.56 to 400 mg/kg of body weight divided 1 to 8 times daily were administered against two methicillin-susceptible S. aureus isolates, two hospital-associated MRSA (HA-MRSA) isolates, and three community-associated (CA-MRSA) isolates. Tigecycline pharmacokinetics were best described by a two-compartment model, with a mean half-life of 9.9 h. Protein binding was dose dependent (range, 92.9 to 81.2%). MICs were 0.25 microg/ml for all isolates, except for HA-MRSA 56 (MIC, 0.5 microg/ml) and CA-MRSA 156 (MIC, 0.125 microg/ml). Tigecycline displayed efficacy against all isolates, producing maximum decreases in log(10) numbers of CFU/ml of 1.8 to 2.3 from 0-h controls. Mean correlation coefficients for free-drug (f) concentration exposures derived from the parameters fT>MIC (the percentage of time during which the concentration of f remains above the MIC), fC(max)/MIC (the ratio of the maximum concentration of f to the MIC), and fAUC/MIC (the ratio of the area under the concentration-time curve of f to the MIC) were 0.622, 0.812, and 0.958, respectively. Values for the mean effective exposure index at 80% (EI(80)) and 50% (EI(50)) for fAUC/MIC were 5.4 microg/ml (range, 2.8 to 13 microg/ml) and 2.6 microg/ml (range, 0.6 to 5.1 microg/ml), respectively. Experiments with nonneutropenic mice infected with CA-MRSA 156 resulted in maximum kill at all fAUC/MIC exposures tested (1.8 to 8.8 microg/ml). The fAUC/MIC ratio is the pharmacodynamic parameter most predictive of tigecycline efficacy. Furthermore, the presence of a functioning immune system markedly reduces the required exposure.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Minocycline; Muscle, Skeletal; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus; Thigh; Tigecycline

Although infections associated with penile implants are relatively infrequent, they result in serious medical consequences. Because treatment of these infections usually requires removal of the infected penile implant, prevention of infection is crucial. Since bacterial colonization of the implant is a prelude to clinical infection, antimicrobial modification of the devices may inhibit device colonization and subsequent infection.. We compared the spectrum and durability, both in vitro and in vivo, of two antibiotic-treated penile prostheses: InhibiZone implants pre-impregnated with minocycline and rifampin (M/R) and Titan implants dipped in vancomycin.. 1×1-cm cylinder segments of (1) control untreated, (2) M/R-impregnated, and (3) vancomycin-dipped implants were studied. Baseline zones of inhibition (ZI) were determined against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), and Escherichia coli. In addition, ZI against methicillin-susceptible S. aureus were compared both in vitro after being washed in a flow chamber and after subcutaneous implantation in rabbits for 1, 2, 7, and 14 d.. ZI were measured as the diameter of the clear zone around each test device minus the external diameter of the device.. Implants pre-impregnated with M/R displayed a broader spectrum of antimicrobial activity than vancomycin-dipped implants against both gram-positive and -negative bacteria. The M/R-impregnated devices also yielded significantly larger zones of inhibition against S. aureus than vancomycin-dipped implants, both in vitro (p<0.003) and in vivo throughout the 14-d period of device implantation in rabbits (p≤0.03).. Penile prostheses impregnated with M/R have a broader spectrum in vitro and a more durable antimicrobial activity in vitro and in an animal model than implants dipped in vancomycin. Therefore, along with being a more practical model for incorporating antimicrobials onto the device, the use of implants pre-impregnated with M/R may help reduce the incidence of penile implant infection.

Topics: Animals; Anti-Bacterial Agents; Drug Implants; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterococcus; Escherichia coli; Escherichia coli Infections; Male; Methicillin-Resistant Staphylococcus aureus; Minocycline; Penile Prosthesis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Topics: Acetamides; Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Daptomycin; Drug Synergism; Humans; Joints; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Staphylococcus; Tigecycline

Twice-daily 7-day regimens of tigecycline (7 mg/kg) and vancomycin (50 mg/kg) were compared in a rat tissue cage model of chronic foreign-body infection due to methicillin (meticillin)-resistant Staphylococcus aureus strain MRGR3. Subcutaneously administered tigecycline reached levels in tissue cage fluid that were nearly equivalent or slightly superior to the antibiotic MIC (0.5 microg/ml) for strain MRGR3. After 7 days, equivalent, significant reductions in bacterial counts were recorded for tigecycline-treated and vancomycin-treated rats, compared with those for untreated animals.

Topics: Animals; Anti-Bacterial Agents; Foreign Bodies; Methicillin-Resistant Staphylococcus aureus; Minocycline; Rats; Staphylococcal Infections; Tigecycline; Vancomycin

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Doxycycline; Enzyme Activators; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tetracycline Resistance

Synthetic vascular conduits used in traumatic or infected fields have a high failure rate leading to catastrophic consequences including amputation and death. Although efforts to coat vascular grafts with antibiotics have had varying results, we developed a novel coating technique for expanded-polytetrafluoroethylene (ePTFE), which has proven to be effective in vitro. Thus, we hypothesized that the coated grafts would resist infection and have decreased neointimal hyperplasia when used in vivo in a large animal model.. Minocycline and rifampin suspended in a mixture of methacrylates were coated onto a 3cm segment of 6mm ePTFE (Bard, Tempe, AZ). An antibiotic-coated (ABX), adhesive-coated (AC), or control (C) ePTFE graft was then placed as an end-to-side graft into the left iliac artery of a male mongrel pig. Sterile saline or innoculum containing 3x10(8)Staphylococcus aureus (SA) or Staphylococcus epidermidis (SE) was then placed directly on the graft and the reflected peritoneum re-approximated to confine the bacteria. After 6 wk, the graft was harvested, cultured, and morphometric analyses of neointimal hyperplasia were performed.. Twenty-seven pigs had grafts placed (9 ABX, 9 AC, 9 C) and harvested. Of the nine grafts exposed to SA, the uncoated and adhesive-coated grafts averaged greater than 50,000 colonies of SA while the antibiotic-coated grafts averaged less than 50 colonies. Although not statistically significant, neointimal hyperplasia was decreased by 15% to 20% when using an ABX graft in an infected field.. The coated grafts appeared to decrease NIH formation although not significantly in this small pilot study. The methacrylate antibiotic-coated ePTFE graft did provide resistance to infection when used in infected fields.

Topics: Adhesives; Animals; Anti-Bacterial Agents; Blood Vessel Prosthesis; Coated Materials, Biocompatible; Disease Models, Animal; Hyperplasia; Male; Methacrylates; Microscopy, Electron, Scanning; Minocycline; Pilot Projects; Polytetrafluoroethylene; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Swine

Glycylcyclines are novel semisynthetic group of antibiotics that have been produced by substitution of glycylamido group at position 9 of tetracyclines. Tigecycline derived from minocycline is the first member of glycylcyclines. This new antibiotic has a broad spectrum of activity against variety of gram-positive and gram-negative bacteria and is not affected by known tetracycline resistance mechanisms. The aim of this study was to investigate the in-vitro activity of tigecycline as well as vancomycin, linezolid, quinupristin-dalfopristin and trimethoprim-sulphamethoxazole (TMP-SMX) against methicillin-resistant staphylococci isolated from clinical specimens of adult patients in Hacettepe University Hospital. For this purpose 127 Staphylococcus aureus (MRSA) and 42 coagulase negative staphylococci (MRCNS) which had been shown to be resistant to methicillin by disc diffusion method performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines, were evaluated. In these isolates minimum inhibitory concentration (MIC) values of tigecycline were detected by E-test; susceptibilities to linezolid, quinupristin-dalfopristin, TMP-SMX were detected by disc diffusion test. All of the isolates were searched for decreased susceptibility to vancomycin by agar screening method and MIC values of vancomycin were detected by E-test for the strains that grew on vancomycin agar plates. The range of MIC values of tigecycline were 0.032-1 microg/ml for the 127 MRSA isolates (MIC50 0.25 microg/ml, MIC90 0.75 microg/ml) and were 0.047-1 microg/ml (MIC50 0.25 microg/ml, MIC90 0.5 microg/ml) for the MRCNS isolates. All staphylococcal isolates were found to be susceptible to vancomycin, linezolid and quinupristin-dalfopristin. TMP-SMX resistance was detected in 7 (5.5%) MRSA and 26 (60.5%) MRCNS isolates. The results of this study demonstrated very good in-vitro activity of tigecycline against both MRSA and MRCNS isolates in our hospital. A remarkable finding of the present study was demonstration of the quite low rate of TMP-SMX resistance among MRSA isolates whereas MRCNS isolates showed high rate of resistance.

Topics: Adult; Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tigecycline

Tigecycline (TGC) is an extended-spectrum antibiotic with activity against Staphylococcus aureus, including methicillin (meticillin)-resistant S. aureus strains, which are well-recognized pathogens in nosocomial pneumonia. The objective of this study was to characterize the exposure-response relationship for TGC against S. aureus in an immunocompromised BALB/c murine pneumonia model. Six S. aureus isolates were studied, and the TGC MICs for those isolates ranged from 0.125 to 0.5 mg/liter. The pharmacokinetics (PK) of TGC in serum and bronchoalveolar lavage (BAL) fluid were evaluated, as was the level of protein binding of the compound in this murine species. Administration of TGC at 1.56 to 150 mg/kg of body weight/day in single or two to three divided doses was used in the efficacy studies. TGC displayed linear PK and had a mean half-life of 10.9 +/- 2.5 h. Efficacy was highly correlated with the area under the free concentration-time curve (fAUC)/MIC (r(2) = 0.93). The 80% and 50% effective exposure indexes and the stasis exposure index were similar between the isolates (means +/- standard deviations, 3.04 +/- 1.12, 1.84 +/- 1.3, and 1.9 +/- 1.5, respectively). Maximal efficacy was predicted at a 2.85-log(10)-CFU reduction. TGC appeared to accumulate in the interstitial space, as the ratios of the fAUC from 0 to 8 h of epithelial lining fluid to plasma were 7.02, 15.11, and 23.95 for doses of 12.5, 25, and 50 mg/kg, respectively. TGC was highly effective in this murine pneumonia model. In light of current MIC distributions, the fAUC/MIC targets that we defined against S. aureus are readily achievable in humans given conventional doses of TGC.

Topics: Animals; Anti-Bacterial Agents; Female; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Minocycline; Pneumonia; Staphylococcal Infections; Tigecycline

We investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in China and determined the susceptibility of S. aureus to 26 antimicrobial agents, including ceftobiprole, linezolid, and tigecycline. A total of 798 isolates were collected and tested by agar dilution. The mean prevalence of MRSA was 50.4%, the highest in Shanghai (80.3%), followed by those in Beijing (55.5%) and Shenyang (50.0%). Only 4.2% to 12.6% of MRSA were susceptible to erythromycin, fluoroquinolones, gentamicin, and tetracycline. All isolates were susceptible to teicoplanin, vancomycin, linezolid, tigecycline, and ceftobiprole.

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; China; Humans; Linezolid; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

Topics: Animals; Anti-Infective Agents; Drug Delivery Systems; Drug Resistance, Bacterial; Minocycline; Osteomyelitis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.

Topics: Abdominal Cavity; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Labeling; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Tigecycline; Treatment Outcome; Young Adult

A total of 1989 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) were susceptibility tested by broth microdilution. Pulsed-field gel electrophoresis, SCCmec type, and polymerase chain reaction for Panton-Valentine leukocidin (PVL) genes were also performed. The overall tigecycline susceptibility rate was 98.2%. Glycopeptides, quinupristin/dalfopristin, linezolid, and chloramphenicol were also active against this collection (< or =0.7% resistant). The vast majority (70.8%) of the CA-MRSA was SCCmec type IV, from which 88.4% belonged to the USA300-0114 clone and 94.7% were PVL positive. Tigecycline showed in vitro activity comparable with other highly active parenteral agents and represents an option for treating complicated infections caused by CA-MRSA.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Bacterial Toxins; Community-Acquired Infections; DNA Fingerprinting; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Exotoxins; Genotype; Humans; Leukocidins; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; North America; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

Some methicillin-resistant Staphylococcus aureus (MRSA) strains in which combinations of vancomycin (VCM) and beta-lactam antibiotics show antagonism have recently emerged, and these strains are called beta-lactam-induced VCM-resistant MRSA (BIVR). We examined whether various antibiotics exhibited an antagonistic effect with VCM when used against Mu3 and Fu10 (representative BIVR strains), using a simple agar disc method. Chloramphenicol, tetracyclines, macrolides, and lincosamides showed an antagonistic effect with VCM. We attempted to elucidate the antagonistic mechanism of a combination of VCM and minocycline (MINO) in BIVR strains. We determined the rates of autolysis, autolytic activities, and the change in morphology of Mu3 treated with a combination of VCM and MINO. We observed that Mu3 grown in a combination of VCM and MINO showed increasing rates of autolysis, and lower minimal bacteriolytic enzyme dose (MBD) values compared with Mu3 grown in VCM alone, but no cell wall thickening was observed. Taken together, these results suggest that cell wall thickening may not be essential in the increased resistance of BIVR strains. Our present data therefore suggest that these combination therapies of VCM with tetracyclines should be adopted with great care in order to prevent VCM treatment failure.

Topics: Anti-Bacterial Agents; Bacteriolysis; Drug Resistance, Multiple, Bacterial; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Vancomycin Resistance

We evaluated the efficacy of tigecycline and teicoplanin in a rat model of MRSA osteomyelitis. Osteomyelitis was induced with an intramedullary injection of 10(8 )colony-forming units (cfu) of MRSA. After osteomyelitis formation was confirmed on Day 14, infected rats were randomly divided into three groups: tigecycline (n=13), teicoplanin (n=13), and no-treatment control (n=14). A 28-day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily) or intramuscular administration of teicoplanin (20 mg/kg daily) was administered. Rats were then sacrificed, and the tibias were harvested. The bones were weighed and then cultured. Our results indicated that bacterial growth was significantly reduced in teicoplanin and tigecycline groups, compared to the control group (p=0.019 and p=0.006, respectively). However, no difference was detected between the two antibiotic groups (p=1.000). No bacterial growth was detected in 7 out of 13 and 9 out of 13 specimens of the teicoplanin and tigecycline treated groups, respectively. Although this result was numerically in favor of tigecycline, the difference was not statistically significant (p=0.427). In conclusion, tigecycline, a novel antibiotic, appears as an effective alternative to teicoplanin in the treatment of osteomyelitis caused by MRSA.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Female; Methicillin Resistance; Minocycline; Osteomyelitis; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Tigecycline; Treatment Outcome

Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen that causes morbidity and mortality worldwide. The options for the treatment of MRSA infections are limited. Linezolid is an antibacterial agent of oxazolidinone group. It has a spectrum limited to gram-positive bacteria. Tigecycline is a broad-spectrum antibiotic of glycylcycline group. A total of 60 MRSA strains isolated from various clinical specimens were included in the study. Minimum inhibitory concentrations (MICs) were determined by Etest method, according to the Clinical and Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) criteria. The MIC(90) was 1 microg/ml for linezolid (range 0.094-4 microg/ml), and 0.38 microg/ml for tigecycline (range 0.032-1 microg/ml). All strains were found to be susceptible to linezolid, and only one strain's MIC value was above the threshold for tigecycline. Tigecycline and linezolid may represent therapeutic options for infections caused by MRSA.

Topics: Acetamides; Anti-Infective Agents; Cross Infection; Humans; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Turkey

Pyogenic liver abscesses are uncommon in clinical practice and are usually polymicrobial in nature, with members of the Enterobacteriacae family often implicated. This report describes the use of tigecycline to treat a liver abscess caused by methicillin-resistant Staphylococcus aureus, which was refractory to therapy with standard antimicrobials.

Topics: Anti-Bacterial Agents; Humans; Liver Abscess; Male; Methicillin Resistance; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Tomography, X-Ray Computed

Since device colonization is a prelude to infection, an antimicrobial-coated device that reduces bacterial colonization can potentially protect against infection. The objective of this animal study was to assess the efficacy of a coating with minocycline and rifampin to prevent colonization of a grit-blasted titanium implant and subsequent osteomyelitis.. Twenty-five rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits) or uncoated (twelve rabbits), into the right femoral medullary canal. The implanted devices were inoculated with 500 CFU (colony-forming units) of Staphylococcus aureus prior to wound closure. The rabbits were killed one week later, and the removed device, femoral bone, a specimen obtained by swabbing the track surrounding the device, and blood were cultured. The rates of device colonization, osteomyelitis, and device-related osteomyelitis were compared between the two groups of rabbits.. The antimicrobial-coated devices had a significantly lower rate of colonization than the uncoated devices (five of thirteen compared with twelve of twelve, p = 0.0016) and were associated with significantly lower rates of osteomyelitis (six of thirteen compared with twelve of twelve, p = 0.005) and device-related osteomyelitis (five of thirteen compared with twelve of twelve, p = 0.0016). Bacteremia did not develop in any rabbit.. Orthopaedic devices coated with minocycline and rifampin significantly protected against device colonization and infection due to Staphylococcus aureus in this in vivo rabbit model.. It is possible that orthopaedic devices coated with this unique combination of antimicrobial agents may protect against the development of clinical infection in humans.

Topics: Animals; Anti-Infective Agents; Drug Delivery Systems; Minocycline; Osteomyelitis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

We evaluated the activity of several antibiotics against 225 clinical isolates of Staphylococcus aureus and 252 isolates of Streptococcus agalactiae. Only tigecycline, glycopeptides, and linezolid were active against all the isolates of S. aureus, whereas the beta-lactams were also active against S. agalactiae. Tigecycline could be a good alternative to ampicillin in the treatment of group B Streptococcus infections in patients allergic to beta-lactam.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus agalactiae; 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

Minocycline exerts beneficial immune modulatory effects in several noninfectious neurodegenerative disease models; however, its potential to influence the host immune response during central nervous system bacterial infections, such as brain abscess, has not yet been investigated. Using a minocycline-resistant strain of Staphylococcus aureus to dissect the antibiotic's bacteriostatic versus immune modulatory effects in a mouse experimental brain abscess model, we found that minocycline significantly reduced mortality rates within the first 24 hours following bacterial exposure. This protection was associated with a transient decrease in the expression of several proinflammatory mediators, including interleukin-1beta and CCL2 (MCP-1). Minocycline was also capable of protecting the brain parenchyma from necrotic damage as evident by significantly smaller abscesses in minocycline-treated mice. In addition, minocycline exerted anti-inflammatory effects when administered as late as 3 days following S. aureus infection, which correlated with a significant decrease in brain abscess size. Finally, minocycline was capable of partially attenuating S. aureus-dependent microglial and astrocyte activation. Therefore, minocycline may afford additional therapeutic benefits extending beyond its antimicrobial activity for the treatment of central nervous system infectious diseases typified by a pathogenic inflammatory component through its ability to balance beneficial versus detrimental inflammation.

Topics: Animals; Anti-Bacterial Agents; Brain Abscess; Chemokine CCL2; Encephalitis; Interleukin-1beta; Mice; Mice, Inbred C57BL; Minocycline; Neuroglia; Staphylococcal Infections; Staphylococcus aureus; Toll-Like Receptor 2

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a surveillance study established in 2004 to monitor the activity of tigecycline, the first glycylcycline, and comparator agents [beta-lactams (including penicillins, cephalosporins and carbapenems), glycopeptides, tetracyclines, fluoroquinolones and oxazolidinones] against Gram-positive and Gram-negative pathogens worldwide. This report examines 1692 isolates of Staphylococcus aureus collected in the continental United States between January 2004 and September 2005. Meticillin-resistant S. aureus (MRSA) accounted for 52.0 % of isolates. Prevalence of MRSA by state ranged from 12.5 % in New Hampshire to 100 % in Kentucky. All isolates were susceptible to tigecycline, linezolid and vancomycin. In vitro, tigecycline was potent against both meticillin-susceptible S. aureus (MSSA) (MIC(50) and MIC(90)=0.12 microg ml(-1)) and MRSA (MIC(50)=0.12 microg ml(-1); MIC(90)=0.25 microg ml(-1)). Only a single isolate was resistant to three or more antimicrobial classes. Ninety-six isolates (5.7%) were susceptible to the complete antimicrobial panel.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Humans; Infant; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Minocycline; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; United States

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is characterized by variations (sometimes extreme) by country and geographic region. The conventional association of MRSA with healthcare settings has been upset by the emergence of community-associated MRSA infections in many areas. With this surge in MRSA comes a renewed interest in alternative agents to vancomycin for treatment of MRSA infections, including older drugs, such as clindamycin, doxycycline and trimethoprim- sulfamethoxazole. Newer agents, such as linezolid and daptomycin, are aiming to improve on the poor cure rates found with vancomycin in serious MRSA infections, but definitive studies showing superiority of these drugs are not yet available. Finally, the drug-development pipeline contains a number of agents for the treatment of MRSA infections, including enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA cephalosporins (ceftobiprole). As MRSA becomes the 'new normal' in many areas, clinicians will have to sort out the proper role of a dozen or more anti-MRSA drugs.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Clindamycin; Daptomycin; Doxycycline; Folic Acid Antagonists; Global Health; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Methicillin; Methicillin Resistance; Minocycline; Oxazolidinones; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Teicoplanin; Tigecycline; Trimethoprim; Vancomycin

An in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms developed on 96-well polystyrene tissue culture plates was performed to elucidate the activity of citropin 1.1, rifampin and minocycline. Efficacy studies were performed in a rat model of staphylococcal CVC infection. Silastic catheters were implanted into the superior cava. Twenty-four hours after implantation the catheters were filled with citropin 1.1 (10 microg/mL). Thirty minutes later the rats were challenged via the CVC with 1.0 x 10(6) CFU of S. aureus strain Smith diffuse. Administration of antibiotics into the CVC (the antibiotic lock technique) began 24 h later. The study included: one control group (no CVC infection), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received citropin 1.1-treated CVC, two contaminated groups that received citropin 1.1-treated CVC plus rifampin and minocycline at concentrations equal to MBCs for adherent cells and 1024 microg/mL in a volume of 0.1 mL that filled the CVC and two contaminated groups that received rifampin or minocycline at the same concentrations. All catheters were explanted 7 days after implantation. Main outcome measures were: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), synergy studies, quantitative culture of the biofilm formed on the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. MICs of conventional antibiotics against the bacteria in a biofilm were at least four-fold higher than against the freely growing planktonic cells. In contrast, when antibiotics were used on citropin 1.1 pre-treated cells they showed comparable activity against both biofilm and planktonic organisms. The in vivo studies show that when CVCs were pre-treated with citropin 1.1 or with a high dose of antibiotics, biofilm bacterial load was reduced from 10(7) to 10(3) CFU/mL and bacteremia reduced from 10(3) to 10(1) CFU/mL. When CVCs were treated both with citropin 1.1 and antibiotics, biofilm bacterial load was further reduced to 10(1) CFU/mL and bacteremia was not detected, suggesting 100% elimination of bacteremia and a log 6 reduction in biofilm load. Citropin 1.1 significantly reduces bacterial load and enhances the effect of hydrophobic antibiotics in the treatment of CVC-associated S. aureus infections.

Topics: Amphibian Proteins; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Biofilms; Catheterization; Catheterization, Central Venous; Male; Microbial Sensitivity Tests; Minocycline; Polystyrenes; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Treatment Outcome

To evaluate the clinical impact, aqueous tear parameters, and meibomian gland morphology in patients with primary meibomianitis before, during, and 3 months after a course of oral minocycline.. 16 patients were prospectively enrolled, 11 male and five female (mean age 69 years old). Each patient received routine clinical evaluations before, after 3 months therapy, and at 6 month study follow up visit. The clinical appearance, tear volume, flow and turnover, evaporation, Schirmer I test, meibomian gland dropout, lissamine green staining, and bacteriology wer evaluated.. Improvement was observed in clinical signs of meibomianitis at the second and third visits. Microbial culture findings improved. Decreased aqueous tear volume and flow, and increased evaporation rate range at 35-45% relative humidity (RH) (p < 0.05) were also detected. Other related tear parameters did not change. Meibomian gland dropout showed no improvement.. 3 months of oral minocycline resulted in clinical improvements in all meibomianitis signs that persisted for at least 3 months after discontinuation despite decreased aqueous tear volume and flow with increased evaporation (35-45% RH). However, there was improvement in the turbidity of secretions. Short term minocycline therapy probably has efficacy in the management of meibomianitis that extends beyond eradication of bacteria.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria, Anaerobic; Conjunctiva; Dry Eye Syndromes; Eyelid Diseases; Female; Humans; Male; Meibomian Glands; Middle Aged; Minocycline; Prospective Studies; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Tears

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Drug Design; Humans; Incidence; Lipoglycopeptides; Methicillin Resistance; Minocycline; Molecular Structure; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Thiazoles; Tigecycline

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Infectious; Drug Delivery Systems; Female; Humans; Knee Joint; Microspheres; Minocycline; Staphylococcal Infections; Vancomycin

The in vitro activities of 22 antimicrobial agents, including ceftobiprole, daptomycin, and tigecycline, against 511 methicillin-resistant Staphylococcus aureus (MRSA) isolates from 112 Belgian hospitals were studied by using the CLSI agar dilution method. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) analysis and by PCR detection of determinants of resistance to aminoglycosides, macrolides-lincosamides-streptogramins, and tetracyclines. A representative set of isolates with different PFGE genotypes was further characterized by multilocus sequence typing, determination of staphylococcal cassette chromosome mec (SCCmec) type, and multiplex PCR for toxic shock syndrome type 1 (TSST-1) and Panton-Valentine leukocidin genes. MRSA isolates belonged to nine epidemic MRSA clones, of which sequence type 45 (ST45)-SCCmec IV and ST8-SCCmec IV were predominant, accounting for 49 and 20% of isolates, respectively. The distribution of antimicrobial resistance and TSST-1 genes was strongly linked to clonal types. Ceftobiprole, daptomycin, and tigecycline showed high activity against all isolates of these sporadic and epidemic MRSA clones, as indicated by MIC(90)s of 2 mg/liter, 0.5 mg/liter, and 0.25 mg/liter, respectively. The MIC distribution of daptomycin and tigecycline was not different in isolates with decreased susceptibility to glycopeptides or tetracyclines, respectively. Ceftobiprole MICs were not correlated with oxacillin and cefoxitin MICs. These data indicate excellent activity of the newly developed agents ceftobiprole, daptomycin, and tigecycline against MRSA isolates recently recovered from hospitalized patients in Belgium, supporting their therapeutic potential for nosocomial MRSA infections.

Topics: Anti-Bacterial Agents; Belgium; Cephalosporins; Daptomycin; Drug Resistance, Bacterial; Exotoxins; Genes, Bacterial; Hospitals; Humans; In Vitro Techniques; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Clindamycin; Community-Acquired Infections; Doxycycline; Humans; Methicillin Resistance; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

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

Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis.. A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed.. Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones.. Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.

Topics: Animals; Bone and Bones; Disease Models, Animal; Drug Therapy, Combination; Methicillin Resistance; Minocycline; Osteomyelitis; Rabbits; Radiography; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin

Topics: Adult; Anti-Bacterial Agents; Bone Diseases; Bone Plates; Color; Female; Femoral Fractures; Humans; Methicillin Resistance; Minocycline; Staphylococcal Infections

It has been known that treatments of post-pneumonectomy empyema are difficult. We report a successful case of irrigation for the post-pneumonectomy. The patient was 68-year-old man with advanced lung cancer. He underwent induction chemoradiotherapy following by pneumonectomy of the right side. A few days later after the chest drain was withdrawn, spike fever appeared. Empyema was suspected, so a 28 Fr diameter double lumen chest drain was intubated again. Turbid effusion was discharged through the drain, in which methicillin-resistant staphylococcus aureus (MRSA) was cultured. Irrigation using a lot of saline and acid electrolyzed water started. A month later, irrigator through the drain was looking clear, however, MRSA was cultured so far. After putting minomycine into the irrigator, MRSA died away. This physical and chemical irrigations were effective.

Topics: Adenocarcinoma; Aged; Empyema, Pleural; Humans; Lung Neoplasms; Male; Methicillin Resistance; Minocycline; Pneumonectomy; Postoperative Complications; Staphylococcal Infections; Therapeutic Irrigation

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bone Marrow Transplantation; Catheterization, Central Venous; Catheters, Indwelling; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance; Female; Humans; Infection Control; Leukemia; Male; Middle Aged; Minocycline; Neutropenia; Rifampin; Staphylococcal Infections; Texas

Tigecycline (GAR-936) and daptomycin are potent antibacterial compounds in advanced stages of clinical trials. These novel agents target multiply resistant pathogenic bacteria. Daptomycin is principally active against gram-positive bacteria, while tigecycline has broad-spectrum activity. When tested by the standard protocols of the National Committee for Clinical Laboratory Standards in Mueller-Hinton broth II, tigecycline was more active than daptomycin (MICs at which 90% of isolates tested are inhibited, 0.12 to 1 and 0.5 to 16 microg/ml, respectively) against staphylococcal, enterococcal, and streptococcal pathogens. Daptomycin demonstrated a stepwise increase in activity corresponding to an increase in the supplemental concentration of calcium. When tested in base Mueller-Hinton broth supplemented with 50 mg of calcium per liter, daptomycin demonstrated improved activity (MIC(90)s, 0.015 to 4 microg/ml). The activity of daptomycin, however, equaled that of tigecycline against the glycopeptide-intermediate Staphylococcus aureus (GISA) strains only when the test medium was supplemented with excess calcium (75 mg/liter). Tigecycline and daptomycin demonstrated in vivo efficacies against GISA, methicillin-resistant S. aureus, and methicillin-susceptible S. aureus strains in an intraperitoneal systemic murine infection model. These data suggest that tigecycline and daptomycin may offer therapeutic options against clinically relevant resistant pathogens for which current alternatives for treatment are limited.

Topics: Animals; Anti-Bacterial Agents; Calcium; Daptomycin; Female; Gram-Positive Bacteria; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Minocycline; Phenotype; Staphylococcal Infections; Staphylococcus aureus; Tigecycline

Because bacterial colonization of medical devices may result in clinical infection, it is conceivable that antimicrobial impregnation of tissue expanders may reduce the rate of infection. The objective of this in vitro study was to examine the spectrum, durability, and shelf-life antimicrobial activity of minocycline/rifampin-impregnated silicone tissue expander shells. The impregnated devices exhibited zones of inhibition at baseline against Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli. The impregnated devices exhibited strong residual activity against S. epidermidis and S. aureus after suspension in serum at 37 degrees C for 4 weeks. There was no significant decrease in the size of zones of inhibition after storing the impregnated devices at room temperature for 1 year. These results indicate that minocycline/rifampin-impregnated tissue expander shells provide broad-spectrum and durable antimicrobial activity and that the shelf-life antimicrobial activity exceeds 1 year. These findings prompt future exploration of the anti-infective efficacy of these antimicrobial-impregnated devices.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibiotics, Antitubercular; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Minocycline; Prosthesis-Related Infections; Rifampin; Silicones; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Tissue Expansion Devices

To assess, in an animal study, the efficacy of minocycline/rifampin-impregnated silicone sections of pump bulbs from penile implants in preventing device colonization by Staphylococcus aureus. Infection constitutes a very serious complication of penile implants.. Minocycline/rifampin-impregnated and control silicone pump bulb sections from penile implants were each inoculated with about 10(3) to 10(4) colony-forming units of S. aureus. After 8 hours of incubation with bacteria at room temperature, the test devices were allowed to dry for 30 minutes, and then subcutaneously implanted in the backs of rabbits. Eleven rabbits each received a total of six devices. The wounds were sutured, and the rabbits were monitored daily, then killed at 2 days after surgery. In vitro zones of inhibition against S. aureus by the minocycline/rifampin-impregnated and control devices were also determined.. All of the six tested antimicrobial-impregnated devices but none of the control devices produced zones of inhibition in vitro against S. aureus (mean zone of inhibition by antimicrobial-impregnated devices of 23 mm). The antimicrobial-impregnated devices retrieved from rabbits were sixfold less likely than were the control devices to be colonized with S. aureus (2 [6%] of 33 versus 11 [33%] of 33, respectively; P = 0.011).. The results of this animal study indicate that minocycline/rifampin-impregnated pump bulb sections from penile implants provide antimicrobial activity in vitro against S. aureus and protect against staphylococcal colonization of devices implanted for 2 days in animals.

Topics: Animals; Anti-Bacterial Agents; Female; Minocycline; Penile Prosthesis; Prosthesis-Related Infections; Rabbits; Rifampin; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus

Bacterial colonization of mammary implants is a prelude to clinical infection and has been implicated in the etiology of capsular contracture. Antimicrobial impregnation of a variety of medical devices with the combination of minocycline and rifampin has recently emerged as a potentially effective method for preventing device colonization and device-related infection. The objective of this animal study was to examine in vivo the antimicrobial efficacy of minocycline/rifampin-impregnated, saline-filled silicone implants. A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously placed implants was used. A total of 48 saline-filled silicone implants (24 antimicrobe-impregnated and 24 control unimpregnated implants) were suspended in a 106 colony-forming units/ml bacterial suspension of S. aureus for 30 minutes at room temperature, allowed to dry for 60 minutes, and then implanted subcutaneously in the back of 12 rabbits (two antimicrobe-impregnated and two control implants were placed in each rabbit). Rabbits were monitored daily, then killed either at 2 weeks (10 rabbits) or at 4 weeks (two rabbits) and cultured. The antimicrobe-impregnated implants were 12 times less likely to be colonized than control unimpregnated implants (two of 24 versus 23 of 24; p < 0.001), and they were a significantly less likely cause of implant-related infection (0 of 24 versus 22 of 24; p < 0.001) and implant-related abscess (0 of 24 versus 21 of 24; p < 0.001) than control implants. The minocycline/rifampin-impregnated implants routinely demonstrated zones of inhibition against S. aureus at the time of explantation. These results indicate that minocycline/rifampin-impregnated implants can significantly decrease the rate of bacterial colonization, implant-related infection, and implant-related abscess. Antimicrobe-impregnated implants also have the potential of reducing the likelihood of capsular contracture.

Topics: Animals; Breast Implants; Female; Minocycline; Prosthesis-Related Infections; Rabbits; Rifampin; Silicones; Specific Pathogen-Free Organisms; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Diabetes Mellitus, Type 1; Humans; Hyperpigmentation; Leg Ulcer; Male; Middle Aged; Minocycline; Prognosis; Staphylococcal Infections

The 9-t-butylglycylamido derivative of minocycline (TBG-MINO) is a recently synthesized member of a novel group of antibiotics, the glycylcyclines. This new derivative, like the first glycylcyclines, the N,N-dimethylglycylamido derivative of minocycline and 6-demethyl-6-deoxytetracycline, possesses activity against bacterial isolates containing the two major determinants responsible for tetracycline resistance: ribosomal protection and active efflux. The in vitro activities of TBG-MINO and the comparative agents were evaluated against strains with characterized tetracycline resistance as well as a spectrum of recent clinical aerobic and anaerobic gram-positive and gram-negative bacteria. TBG-MINO, with an MIC range of 0.25 to 0.5 microgram/ml, showed good activity against strains expressing tet(M) (ribosomal protection), tet(A), tet(B), tet(C), tet(D), and tet(K) (efflux resistance determinants). TBG-MINO exhibited similar activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and vancomycin-resistant enterococci (MICs at which 90% of strains are inhibited, < or = 0.5 microgram/ml). TBG-MINO exhibited activity against a wide diversity of gram-negative aerobic and anaerobic bacteria, most of which were less susceptible to tetracycline and minocycline. The in vivo protective effects of TBG-MINO were examined against acute lethal infections in mice caused by Escherichia coli, S. aureus, and Streptococcus pneumoniae isolates. TBG-MINO, administered intravenously, demonstrated efficacy against infections caused by S. aureus including MRSA strains and strains containing tet(K) or tet(M) resistance determinants (median effective doses [ED50s], 0.79 to 2.3 mg/kg of body weight). TBG-MINO demonstrated efficacy against infections caused by tetracycline-sensitive E. coli strains as well as E. coli strains containing either tet(M) or the efflux determinant tet(A), tet(B), or tet(C) (ED50s, 1.5 to 3.5 mg/kg). Overall, TBG-MINO shows antibacterial activity against a wide spectrum of gram-positive and gram-negative aerobic and anaerobic bacteria including strains resistant to other chemotherapeutic agents. The in vivo protective effects, especially against infections caused by resistant bacteria, corresponded with the in vitro activity of TBG-MINO.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Tetracycline Resistance; Tetracyclines; Tigecycline

Clarithromycin, a macrolide antibiotic not previously tested against the common causes of bacterial keratitis, was analyzed for its effectiveness in reducing the number of viable bacteria in a Staphylococcus keratitis model. An in vivo comparison of the effectiveness of clarithromycin to erythromycin, minocycline, and tetracycline for three strains of Staphylococcus aureus was done.. Rabbit eyes were intrastromally injected with 100 colony forming units of one of three strains of S. aureus. Two strains were methicillin-sensitive (ATCC 25923 and MSSA 309) and one strain methicillin-resistant (COL). Eyes were treated every 30 minutes with 0.3% clarithromycin, erythromycin, tetracycline, or minocycline from 4 to 9 hours postinfection. The number of colony forming units (CFU) per cornea in all eyes was determined at 10 hours postinfection.. Vehicle-treated and untreated eyes (controls) contained over 6 logs of CFU per cornea, a value significantly higher than any of the antibiotic-treated eyes (P < or = 0.0001). Clarithromycin or erythromycin therapy significantly decreased the number of CFU per cornea by approximately 5 logs in the eyes infected with the methicillin-sensitive strains and by approximately 4 logs in the eyes infected with the methicillin-resistant strain. Tetracycline and minocycline were also successful in treating these strains, but overall showed less effectiveness than clarithromycin and erythromycin.. Clarithromycin proved to be an effective ocular medication for the therapy of experimental S. aureus keratitis. The effectiveness of clarithromycin in this model and its known effectiveness for a variety of bacterial pathogens suggests a role for this drug as a useful ocular antibiotic.

Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Colony Count, Microbial; Erythromycin; Keratitis; Minocycline; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Tetracycline

The incidence of cutaneous bacterial infection after carbon dioxide (CO2 laser resurfacing is increasing. Patients with staphylococcal colonization of their anterior nares may be at greater risk for postoperative cutaneous colonization and/or infection, which can potentially cause scarring.. We present a case report of methicillin-resistant Staphylococcus aureus secondary infection of the skin after CO2 laser resurfacing. We discuss the possible etiologies of this patient's infection, her postoperative management, and preoperative suggestions for possibly preventing infection.. A 49-year-old woman was treated with CO2 laser resurfacing for moderate actinic damage and facial rhytides. She developed a cutaneous infection with methicillin-resistant S. aureus, which caused diffuse linear scarring on her cheeks and upper lip.. The patient was successfully treated with oral minocycline, rifampin, and topical mupiricin ointment to her cutaneous erosions.. We propose that it would be helpful for patients undergoing CO2 laser resurfacing to have their nares cultured to see if they are staphylococcal carriers. If a patient is found to be a carrier, mupiricin ointment can be used preoperatively treat to the nares, to help decrease the risk of infection of the skin from this potential source.

Topics: Dermatologic Surgical Procedures; Drug Therapy, Combination; Facial Dermatoses; Female; Humans; Laser Therapy; Methicillin Resistance; Middle Aged; Minocycline; Mupirocin; Rifampin; Skin Aging; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus aureus; Surgery, Plastic; Surgical Wound Infection

Antimicrobial coating of medical devices has recently emerged as a potentially effective method for preventing device-related infections. The objective of this animal study was to examine in vivo the antimicrobial efficacy of prosthetic heart valve sewing ring fabric coated with: (i) silver; (ii) combined minocycline and rifampin (M/R); or (iii) combined chlorhexidine and chloroxylenol (CH/CX).. A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously implanted fabric of prosthetic heart valve sewing rings was used. Following administration of anesthesia and preoperative antibiotic prophylaxis, 0.5 x 0.5 cm samples of fabric were placed subcutaneously into the back of rabbits. Each rabbit received a total of eight samples: (i) two uncoated; (ii) two silver-coated; (iii) two M/R-coated; and (iv) two CH/CX-coated. After injecting a bacterial inoculum of 2 x 10(5) c.f.u. of S. aureus onto each implanted sample, the wounds were sutured. Rabbits were monitored daily for one week, killed and the test fabrics removed and cultured.. Rates of device colonization, device-related infection and device-related abscess were similar between the uncoated and silver-coated devices. Devices coated with M/R were less likely to be colonized or cause device-related infection when compared with uncoated devices, and less likely to be associated with abscess formation than silver-coated devices. There was a tendency for CH/CX-coated devices to be less colonized than uncoated devices. Only M/R-coated and CH/CX-coated devices produced zones of inhibition in vitro. Implantation of M/R-coated and CH/CX-coated devices in rabbits did not result in detectable systemic concentrations of the antimicrobial coating agents. Colonization of antimicrobial-coated devices was not associated with resistant S. aureus isolates.. These results suggest that silver-coated sewing rings may not prove to be clinically anti-infective. In contrast, antimicrobial-coated sewing rings that produce effective zones of inhibition, particularly those coated with M/R, are likely to be clinically protective.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Bacterial Adhesion; Chlorhexidine; Coated Materials, Biocompatible; Colony Count, Microbial; Disease Models, Animal; Drug Combinations; Female; Heart Valve Prosthesis; Minocycline; Prosthesis Design; Prosthesis-Related Infections; Rabbits; Rifampin; Silver Sulfadiazine; Staphylococcal Infections

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

Absorbable, polyglycolic acid (PGA) beads were evaluated as a new vehicle for local antibiotic delivery. Incisions on the dorsa of guinea pigs were contaminated with 1 x 10(8) Escherichia coli and 1 x 10(8) Staphylococcus aureus. PGA beads containing either minocycline, amikacin, or no antibiotic (placebo) were placed into these wounds and compared to animals treated with systemic minocycline or amikacin alone. The diameter of wound erythema was measured daily for 7 days. Serial blood and wound quantitative cultures were obtained, and serum and wound antibiotic concentrations were determined. Both minocycline-PGA and amikacin-PGA-treated wounds exhibited less erythema than placebo-PGA wounds (P < 0.05). All minocycline-PGA and amikacin-PGA-treated wounds healed primarily, whereas 67 per cent of placebo-PGA wounds developed purulence, dehisced, and healed secondarily. Local antibiotic delivery was more effective than systemic administration in reducing wound erythema and the number of bacteria in wound quantitative cultures. E. coli and S. aureus were quantitatively reduced (P < 0.05) in wounds of antibiotic PGA-treated animals compared to those in placebo-PGA-treated and systemic minocycline and systemic amikacin-treated animals. Measurable minocycline and amikacin concentrations were present in antibiotic-PGA-treated wounds through day 3, without detectable serum levels. Delayed-release, absorbable, antibiotic-containing PGA beads effectively prevent infection in contaminated wounds and have the advantage of not requiring vehicle removal.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Drug Implants; Escherichia coli Infections; Guinea Pigs; Male; Minocycline; Polyglycolic Acid; Staphylococcal Infections; Surgical Wound Infection

Treatment of orthopaedic device related infections with antibiotics alone generally has been thought to be inadequate. A rabbit model was used to compare the efficacy of 4 different antibiotic regimens for treating orthopaedic device related infection caused by slime producing Staphylococcus epidermidis. After bacterial inoculation of a hole drilled through the intercondylar notch, a stainless steel screw was placed into the femur. Two weeks later, rabbits were randomized to receive a 2-week course of antibiotics: (1) 9 rabbits received vancomycin alone; (2) 10 rabbits received minocycline alone; (3) 10 rabbits received vancomycin plus rifampin; and (4) 10 rabbits received minocycline plus rifampin. Quantitative bone cultures were performed, and antibiotic levels in serum, bone, and biofilm were determined. Despite high levels of vancomycin in biofilm, infection was never cured by vancomycin alone and was eradicated in only 20% of rabbits that received minocycline alone. The highest cure rate (90%) was achieved with the combination of vancomycin and rifampin, whereas the combination of minocycline and rifampin yielded a cure rate of 70%. These results encourage the clinical evaluation of the combination of vancomycin and rifampin in patients in whom infected orthopaedic device cannot be removed.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Minocycline; Prosthesis-Related Infections; Rabbits; Random Allocation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

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

The purpose of this study was to determine the penetration of minocycline and vancomycin into cardiac vegetations and to determine their efficacy in a rabbit model of endocarditis caused by oxacillin-resistant Staphylococcus aureus. Animals were randomized into three groups: control (no antibiotic), minocycline (6 mg/kg given intravenously every 8 h), and vancomycin (50 mg/kg given intravenously every 8 h). Penetration of the antibiotics into aortic valve vegetations was determined by using the tissue/serum area under the concentration-time curve ratio. The reductions in the bacterial density of the vegetations caused by both vancomycin (4.8 +/- 1.2 CFU/g) and minocycline (5.3 +/- 1.6 CFU/g) were significantly different from that of controls (8.7 +/- 1.8 CFU/g). Although the penetration of minocycline was twice that of vancomycin, they were equally effective in reducing the bacterial density of the vegetations, since the concentrations of both agents in tissue remained above their MICs for oxacillin-resistant S. aureus. For organisms for which the MICs are higher, however, these penetration differences may result in treatment differences.

Topics: Animals; Aortic Valve; Endocarditis, Bacterial; Female; Microbial Sensitivity Tests; Minocycline; Oxacillin; Penicillin Resistance; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Tissue Distribution; Vancomycin

We analyzed the efficacy of arbekacin (ABK) using monotherapy or combined therapy on deep MRSA infection to find the most adequate usage of the drug. We also followed-up the isolation incidence of MRSA after the end of chemotherapy. The results are summarized as follows: 1. Clinical efficacy of ABK on 29 pneumonia and 3 septicemia due to MRSA was 42.9% in ABK monotherapy (9 patients), 62.5% in combined therapy with ABK and minocycline (9 patients), 100% with ABK and imipenem/cilastatin (IPM/CS) (7 patients), and 100% with ABK and other drugs (7 patients). 2. As for microbiological efficacy, combined therapy with ABK and IPM/CS or other drug was superior to other methods. Among patients from whom two or more species of bacteria were isolated, causative bacteria persisted in many cases, and some replacements occurred. 3. Kidney functions deteriorated in two patients that underwent monotherapy or combined therapy with ABK and IPM/CS, but they recovered when therapy was completed the completion. 4. In the three month follow-up study after ABK therapy, we found four cases of renewed infections after disappearance of MRSA. When just decreases in the number of MRSA resulted upon the chemotherapy, the relapse occurred in all cases. 5. Above results indicate that ABK is effective in MRSA infection, and combined therapy with beta-lactams is superior to other methods in serious MRSA infections. We also suggest that chemotherapy should be continued until the complete disappearance of MRSA is achieved.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Cilastatin; Dibekacin; Female; Follow-Up Studies; Humans; Imipenem; Kidney; Male; Methicillin Resistance; Middle Aged; Minocycline; Recurrence; Staphylococcal Infections; Staphylococcus aureus

Susceptibilities to antibiotics were determined in 36 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from clinical specimens from 1990 to 1992. Rates of resistance to arbekacin and minocycline were 31% and 53%, respectively. However, all MRSA isolates were susceptible to vancomycin. MRSA was found in 12 out of 35 cases. Three infections caused by MRSA included enterocolitis (3), abscess (5), pneumonia (1), cholangitis (1), peritonitis (1) and catheter related sepsis (1). In two cases patients died with bacteremia within two years after the onset of MRSA infections.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Female; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Minocycline; Postoperative Complications; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Adult; Drainage; Drug Therapy, Combination; Humans; Liver Abscess; Male; Methicillin Resistance; Minocycline; Povidone-Iodine; Staphylococcal Infections; Staphylococcus aureus

A big problem of nosocomial infections is some refractory infections, so that present important nosocomial infections are deep infections by MRSA and weakly virulent gram-negative bacilli such as Pseudomonas aeruginosa, which are not susceptible to many antimicrobial agents. It is also noteworthy that MRSA can infect to both immunonormal and immunocompromised patients, although clinical signs of that infection are much more severe in the latters. On the other hand, weakly virulent bacilli can infect to only immunocompromised patients. Immunocompromised states are divided into two categories, namely general and local deficiencies. The mechanism of general immunodeficiency is mainly depend upon leukopenia or diminishment of phagocytic activity of them, and that of local immunodeficiency is bases on formation of biofilms which protect bacteria from phagocytosis and killing effect of antimicrobial agents. In this paper, it is emphasized that both countermeasure for nosocomial infections and adequate use of antimicrobial agents or immunomodulators are necessary to decrease number of patients with hospital infections.

Topics: Cross Infection; Disinfection; Granulocyte Colony-Stimulating Factor; Humans; Methicillin Resistance; Minocycline; Premedication; Pseudomonas Infections; Staphylococcal Infections; Vancomycin

Scattering Vitamin C of a small dose on a bedsore, enhances remarkably bactericidal effect of antibiotics. With scattering of it, 1% cream of Sulfadiazine made antibiotics-resistant bacteria (Methicillin-resistant Staphylococcus aureus = MRSA, Pseudomonas aeruginosa etc.) negative on a bedsore. Also in MRSA-infection of respiratory organs, combined administration of Vitamin C gives more effective bactericidal efficacy to some antibiotics. In a case infected with MRSA, of which the Minocycline-therapy had been ineffective, the combined administration of Vitamin C with Minocycline led him successfully to the negativeness of MRSA.

Topics: Administration, Oral; Administration, Topical; Aged; Aged, 80 and over; Ascorbic Acid; Drug Therapy, Combination; Female; Humans; Male; Methicillin Resistance; Minocycline; Pressure Ulcer; Respiratory Tract Infections; Staphylococcal Infections

Topics: Adult; Cefmetazole; Drug Therapy, Combination; Female; Humans; Imipenem; Methicillin Resistance; Minocycline; Ofloxacin; Puerperal Infection; Scarlet Fever; Staphylococcal Infections

In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful.

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Humans; Infection Control; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Mupirocin; Plasmids; Rifampin; Staphylococcal Infections; Staphylococcus aureus

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: Cefotiam; Cross Infection; Drug Therapy, Combination; Glycopeptides; Humans; Imipenem; Methicillin Resistance; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin

Four cases of postoperative meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA) are reported together with a review of the literature. These 4 cases were treated successfully by intravenous administration of minomycin, fosfomycin, and cefmetazole. Factors associated with the development of meningitis included multiple craniotomies, the presence of ventricular drainage or a ventriculo-peritoneal shunt, and irradiation.

Topics: Adult; Cefmetazole; Drug Therapy, Combination; Fosfomycin; Humans; Injections, Intravenous; Male; Meningitis; Methicillin Resistance; Middle Aged; Minocycline; Postoperative Complications; Staphylococcal Infections; Staphylococcus aureus

Topics: Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Middle Aged; Minocycline; Staphylococcal Infections; Tetracyclines

Assessment has been made, using MIC values and coagulase types, of 214 strains of Staphylococcus aureus isolated from the lesions of inpatients at the First Surgical Department, Hiroshima University, from 1983 to 1988. The obtained results are summarized below: 1. Frequency of MRSA among all the strains of S. aureus during a period from 1983 to 1987 was higher than 50%. 2. Highly methicillin-resistant strains (MIC of methicillin greater than 100 micrograms/ml) emerged in 1984 and thereafter, showed a trend of increase through 1987. 3. The highly methicillin-resistant strains are of coagulase II type strain and they are considered to be inhospital epidemic strains. 4. Both ofloxacin and minocycline (MINO) showed good activities against highly methicillin-resistant strains, but many resistant strains were resistant to beta-lactam and aminoglycoside agents. Based on the above basic assessment, chemotherapies mainly using MINO were performed on cases of MRSA infections experienced at the First Surgical Department, Hiroshima University in a period from July, 1987, to November, 1988, and the following results were obtained. 1. Drugs used were: single MINO in 2 cases; MINO+imipenem/cilastatin (IPM/CS) in 4 cases; MINO+IPM/CS+tobramycin in 1 case; MINO+cefmetazole (CMZ) in 1 cases; and MINO+fosfomycin+CMZ (changed to MINO+Amikacin) in 1 case, a total of 9 cases. Clinical result showed remarkable effectiveness of these therapies in 3 cases with some degrees of effectiveness in 6 cases, thus the therapies were all effective or better. 2. No particular abnormality was observed in subjective or objective symptoms or clinical laboratory tests, judged from values obtained before and after administration of MINO. The above results agreed with well those of the basic assessment, suggesting the possibility that the chemotherapies mainly using MINO would exhibit effectiveness on MRSA infections.

Topics: Adult; Aged; Cefmetazole; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Male; Methicillin; Middle Aged; Minocycline; Penicillin Resistance; Postoperative Complications; Staphylococcal Infections; Staphylococcus aureus; Stomach Neoplasms; Tetracyclines

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: Child, Preschool; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Methicillin; Minocycline; Mitral Valve; Mitral Valve Insufficiency; Penicillin Resistance; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines

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

Incidence of cephalosporin-resistant staphylococcal infections is increasing recently. We tried to find out the possible first choice antibiotic for these infections. We estimated minimal inhibitory concentrations (MIC) of each one of the broad spectrum antibiotics with different mode of actions as well as representative drugs of penicillins and cephalosporins against strains of Staphylococcus epidermidis and Staphylococcus aureus. Trend of antibiotic susceptibility of S. epidermidis was found to be as same as that of S. aureus. MIC of minocycline was found to be the lowest in the drugs tested, and there found no resistant strains. MIC of erythromycin was next low but more than a half strains were found to be resistant to this drug. Some of the strains were thought to be treated with amikacin or sulfonamides by the MIC against them, but there also found many resistant strains. Therefore, use of these drugs should be decided after sensitivity test of the causative bacteria. Most of the strains were found not to be treated with beta-lactam antibiotics. In conclusion, minocycline could be the only one first choice drug for staphylococcal infections before antibiotic susceptibility test of the causative strains in the present moment.

Topics: Cephalosporins; Humans; Minocycline; Penicillin Resistance; Penicillins; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

During an outbreak, 25 severely impaired patients (mean age 62) presented with severe infections due to Staphylococcus aureus resistant to oxacillin and aminoglycosides. All strains were isolated in pure culture and diagnostic procedures included transtracheal puncture and bone biopsy. Median MICs were: oxacillin 50 mg/l, gentamicin 12.5 mg/l, tetracycline 25 gm/l, vancomycin 0.195 mg/l, rifampicin 0.097 mg/l and minocycline 0.195 mg/l. All patients were treated with rifampicin (600 mg/day) and minocycline (200 mg or 400 mg/day) administered together intravenously or orally bid. Mean duration of treatment was 22 days (range 5 to 119). Overall results were 19/25 infections cured and one improved. Five were failures due mostly to emergence of Staph. aureus resistant to rifampicin. No side effects were noted. These preliminary results suggest that rifampicin plus minocycline may be useful in the treatment of severe infections due to multi-resistant Staph. aureus.

Topics: Adolescent; Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Rifampin; Staphylococcal Infections; Tetracyclines; Urinary Tract Infections

Topics: Drug Resistance, Microbial; Meningococcal Infections; Minocycline; Molecular Conformation; Staphylococcal Infections; Tetracyclines

1) A focal infection was prepared by inoculation of staphylococci into rat gingiva. Then, concentrations in oral tissues (gingiva, tongue and masseter), serum and liver of the infected rats which were given ciclacillin, ampicillin, cephalexin and minocycline in a dose of 100 mg/kg p.o. were investigated and effects of serratiopeptidase (20 mg/kg) on these concentrations were studied. 2) Concentrations of ciclacillin in the oral tissues were approximately 10% of a serum level. A gingival concentration was elevated 8.5-fold by pretreatment with serratiopeptidase. A concentration in infected gingiva was 2.5-fold of that of another side of gingiva. 3) Concentrations of ampicillin in the oral tissues were approximately 15% of a serum level. A gingival concentration was elevated 5.7-fold by pretreatment with serratiopeptidase. A concentration in infected gingiva ws 2.2-fold of that of another side of gingiva. 4) Concentrations of cephalexin in the oral tissues were approximately 3 to 5-fold of a serum level except that in masseter. A gingival concentration was slightly elevated (1.1-fold) by pretreatment with serratiopeptidase. A concentration in infected gingiva was 1.7-fold of that of another side of gingiva. 5) Concentrations of minocycline in the oral tissues were 1.3 to 7.2-fold of a serum level. A gingival concentration was elevated 2.2-fold by pretreatment with serratipeptidase. A concentration in infected gingiva was 3.1-fold of that of another side of gingiva. 6) Gingival concentrations of antibiotics were higher than those of tongue and masseter and serratiopeptidase elevated gingival concentrations.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Cephalexin; Cyclacillin; Liver; Male; Minocycline; Mouth; Peptide Hydrolases; Rats; Staphylococcal Infections; Tissue Distribution

Of 19 recently isolated cultures of methicillin-resistant Staphylococcus aureus, 18 showed inducible low-level resistance to minocycline, 15 showed high-level resistance to streptomycin, and 4 showed resistance to low levels of streptomycin. Two cultures produced yellow pigment and may have been derived in vivo by loss of a gene(s) determining orange pigment. Treatment of three cultures with serial exposures to N-methyl-N'-nitro-N-nitrosoguanidine resulted in a widening of phage typing pattern that included all reactions in group I, the great majority in group III, but none in group II. The widening in phage lysis was possibly due to the elimination of defective prophages. Transfer of tetracycline resistance occurred from 12 out of the 19 cultures to a recipient in mixed culture; this transfer required either Ca2+ or Mg2+, was abolished by citrate, and enhanced by high cell density. It was probably mediated by defective bacteriophages. No evidence was obtained for the occurrence of recombination within the methicillin-resistant clone in nature. Eleven methicillin-resistant cultures stored for at least 5 years on agar slopes at 20 degrees C had all lost this resistance at high frequency.

Topics: Anti-Bacterial Agents; Bacteriophage Typing; Humans; Methicillin; Minocycline; Mutation; Penicillin Resistance; Pigments, Biological; Recombination, Genetic; Staphylococcal Infections; Staphylococcus aureus; Streptomycin

Susceptibility of 983 isolates of Staphyloccus aureus to tetracycline, doxycycline and minocycline was determined in vitro. Minocycline was shown to be more active than doxycycline, which in turn was shown to be slightly more active than tetracycline. 77% of the isolates which were resistant to tetracycline were also resistant to doxycycline, whereas only 4% of the tetracycline-resistant isolates were resistant to minocycline. The in vivo use of tetracycline correlated with increased in vitro resistance of S. aureus to tetracycline and doxycycline. A correlation between use of tetracycline and in vitro resistance to minocycline was not demonstrated.

Topics: Doxycycline; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tetracycline; Tetracyclines

Topics: Adult; Child; Cloxacillin; Humans; Microbial Sensitivity Tests; Minocycline; Penicillin Resistance; Staphylococcal Infections; Staphylococcus aureus; Tetracycline; Tetracyclines; Time Factors

Fifteen patients who had severe Staphylococcus aureus infections were treated with minocycline for 6 to 24 days; all responded satisfactorily. Where possible, posttherapy cultures were taken, and in all instances, the pathogen was eradicated. There was no adverse reactions. Minocycline proved to be an acceptable and effective alternative for staphylococcal soft-tissue infections. It has the following advantages: (1) it is administered orally on a twice-daily dosage schedule, which facilitates patient compliance; (2) its toxicity is well defined and is not troublesome during short-term therapy; and (3) it penetrates tissues in therapeutic amounts and yields serum levels that are well above the minimum inhibitory concentrations of most staphylococci.

Topics: Adult; Aged; Blood Cell Count; Body Temperature; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Penicillin Resistance; Penicillins; Staphylococcal Infections; Staphylococcus; Tetracycline; Tetracyclines

Ten patients with soft-tissue infections due to Staphylococcus aureus were treated with minocycline, a semisynthetic tetracycline with potent in vitro antistaphylococcal effects. Serum concentrations averaged three to five times the concentration of minocycline required to inhibit growth of S. aureus in vitro. Clearing of the infecting organism was slow (less than 50% of lesions were sterile on day 10 of therapy), but clinical improvement was noted in 8 of 10 patients.

Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Minocycline; Soft Tissue Infections; Staphylococcal Infections

Topics: Doxycycline; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Staphylococcus; Tetracycline

Topics: Focal Infection, Dental; Humans; Minocycline; Staphylococcal Infections; Tetracyclines

Topics: Adult; Drug Resistance, Microbial; Erythromycin; Humans; Male; Minocycline; Osteomyelitis; Penicillin Resistance; Staphylococcal Infections; Tetracycline

Topics: Adolescent; Child; Child, Preschool; Female; Furunculosis; Humans; Infant; Male; Microbial Sensitivity Tests; Minocycline; Otitis Media; Otorhinolaryngologic Diseases; Pneumococcal Infections; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Tonsillitis