minocycline and Staphylococcal-Skin-Infections

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

Treatment of uncomplicated skin and soft-tissue abscesses caused by meticillin-sensitive Staphylococcus aureus or meticillin-resistant S. aureus (MRSA) is problematic. Incision and drainage aside, oral antibiotic therapy for uncomplicated community-acquired MRSA (CA-MRSA) is limited and frequent choices include clindamycin, doxycycline or trimethoprim-sulfamethoxazole (TMP-SMX). The most common oral antibiotics used for CA-MRSA are doxycycline or TMP-SMX, which often fail to eradicate the infection. With MRSA, in vitro susceptibilities do not always predict in vivo effectiveness. In situations where doxycycline or TMP-SMX fails in the treatment of uncomplicated cutaneous abscesses due to CA-MRSA, minocycline is reliably effective.

Topics: Abscess; Administration, Oral; Anti-Bacterial Agents; Community-Acquired Infections; Doxycycline; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections; Tigecycline; Treatment Outcome

In the present review, the authors focus on skin and soft tissue infections (SSTIs), a set of commonly observed pathologies which can present different features in terms of site and localization, clinical characteristics, and the aetiological agent responsible; their severity is related to the depth of the affected sites. After a brief introduction to the diverse classification criteria which are currently adopted by various authors, the aetiology and role of the most frequently occurring pathogen, Staphylococcus aureus, often methicillin-resistant is discussed, as well as the possible therapeutic options. We first present the internationally recommended guidelines, and stress that SSTI management has to conform to different criteria, in accordance with the different clinical settings: mild infections require simple and cost-saving treatments while severe infections make timely and aggressive treatments mandatory. The review then reports the recent data concerning the efficacy of new antimicrobials for treating SSTIs. In particular, results observed with linezolid, tigecycline, and daptomycin are discussed.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Daptomycin; Humans; Linezolid; Methicillin Resistance; Middle Aged; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Skin Diseases, Infectious; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Tigecycline; Time Factors; Treatment Outcome

Although minocycline is not licensed for use in dogs, this tetracycline has therapeutic potential against meticillin-resistant Staphylococcus pseudintermedius.. The aim of this study was to establish rational dosage recommendations for minocycline use in dogs. Specific objectives were to generate and analyse minocycline pharmacokinetic (PK) data on plasma and interstitial fluid (ISF) concentrations, plasma protein binding and pharmacodynamic (PD) data on antimicrobial activity against S. pseudintermedius.. Six healthy dogs from a research colony were used in this study.. Dogs were administered 5 mg/kg intravenously and 10 mg/kg orally (p.o.) of minocycline hydrochloride in separate crossover experiments. In vivo drug concentrations in plasma and in ISF collected by ultrafiltration were measured by high-performance liquid chromatography. Pharmacokinetic analysis was performed on plasma and ISF concentrations. PK/PD analysis was completed using in vitro data on plasma protein binding and minocycline susceptibility in 168 S. pseudintermedius isolates.. Minocycline distributed to the ISF to a higher degree than predicted by the protein-unbound fraction in plasma. A large volume of distribution after oral administration, with plasma and ISF elimination half-lives of 4.1 and 7.4 h, respectively, demonstrated that the ISF serves as a drug reservoir for sustained tissue concentrations. Monte Carlo simulation, used to assess target attainment at different drug dosages, indicated that p.o. administration of 5 mg/kg twice daily is sufficient to inhibit S. pseudintermedius strains with minimal inhibitory concentrations ≤0.25 μg/mL.. Besides dosage recommendations for therapy of meticillin-resistant Staphylococcus pseudintermedius infections in dogs, the study also provides PK/PD data necessary to consider species-specific clinical breakpoints for minocycline susceptibility testing.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cross-Over Studies; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Half-Life; Methicillin Resistance; Minocycline; Staphylococcal Skin Infections; Staphylococcus; Tissue Distribution

Only few data are available on the efficacy of tigecycline in critically ill patients.. This prospective, multicenter, non-interventional study investigated the efficacy and safety of tigecycline in hospitalized, severely ill patients with complicated intra-abdominal infections (cIAI) and/or complicated skin and soft tissue infections (cSSTI). Documentation included diagnosis, clinical findings, Acute Physiology and Chronic Health Evaluation II score, laboratory assessments, surgery, clinical outcomes, and adverse events.. Six hundred and fifty-six patients (mean Acute Physiology and Chronic Health Evaluation II score 19.1) with cIAI (41%), cSSTI (16%), multiple infection sites (13%) and/or other severe infections (31%) received tigecycline - 51% as monotherapy - due to failure of previous antibiotics (55%) or since resistant pathogens were suspected or proven (45%); clinical cure/improvement rates were 75, 82, 76 and 67% for cIAI, cSSTI, other severe infections and multiple infection sites, respectively. Drug-related adverse events occurred in 6.7% of patients.. The efficacy and safety of tigecycline was demonstrated in a population of severely ill patients with complicated infections.

Topics: Aged; Anti-Bacterial Agents; Escherichia coli; Female; Germany; Humans; Infections; Male; Middle Aged; Minocycline; Prospective Studies; Severity of Illness Index; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Tigecycline; Treatment Outcome

Exposure-response analyses were performed for the microbiological and clinical efficacy of tigecycline in the treatment of complicated skin and skin-structure infections, where Staphylococcus aureus and streptococci are the predominant pathogens. A prospective method was developed to create homogeneous patient populations for PK-PD analyses. Evaluable patients from three clinical trials were pooled for analysis. Patients received a tigecycline 100-mg loading dose/50 mg every 12 h or a 50-mg loading dose/25 mg every 12 h. At the test-of-cure visit, microbiologic and clinical responses were evaluated. Patients were prospectively evaluated and classified into cohorts based on baseline pathogens: S. aureus only (cohort 1), monomicrobial S. aureus or streptococci (cohort 2), two gram-positive pathogens (cohort 3), polymicrobial (cohort 4), or other monomicrobial infections (cohort 5). A prospective procedure for combining cohorts was used to increase the sample size. Logistic regression evaluated steady-state 24-h area under the concentration-time curve (AUC(24))/MIC ratio as a predictor of response, and classification and regression tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with pooled cohorts 2 and 3, the focus of these analyses, and included 35 patients with 40 S. aureus and/or streptococcal pathogens. CART analyses identified a significant AUC/MIC breakpoint of 17.9 (P = 0.0001 for microbiological response and P = 0.0376 for clinical response). The continuous AUC/MIC ratio was predictive of microbiological response based on sample size (P = 0.0563). Analysis of all pathogens combined decreased the ability to detect exposure-response relationships. The prospective approach of creating homogeneous populations based on S. aureus and streptococci pathogens was critical for identifying exposure-response relationships.

Topics: Adult; Aged; Anti-Bacterial Agents; Area Under Curve; Double-Blind Method; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Tigecycline; Treatment Outcome

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

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Cellulitis; Drug Therapy, Combination; Drugs, Chinese Herbal; Humans; Male; Minocycline; Scalp Dermatoses; Skin Diseases, Genetic; Staphylococcal Skin Infections; Staphylococcus aureus; Staphylococcus epidermidis; Treatment Outcome

We evaluated the antimicrobial susceptibility of 1,454 organisms consecutively collected from patients with bacteremia associated with skin and skin structure infections. The most common organisms obtained wereStaphylococcus aureus(670 organisms [46.1%]),Escherichia coli(200 organisms [13.8%]), β-hemolytic streptococci (βHS) (138 organisms [9.5%]), andKlebsiella pneumoniae(109 organisms [7.5%]). The susceptibility rates for ceftaroline were 97.9% forS. aureus(95.9% among methicillin-resistantS. aureus[MRSA]), 100.0% for βHS, 86.5% forE. coli, and 89.0% forK. pneumoniae Ceftaroline and tigecycline provided the best overall coverage.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Community-Acquired Infections; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Skin; Staphylococcal Skin Infections; Streptococcal Infections; Streptococcus; Tigecycline; United States

Majority of the chronic wounds are infected with bacteria like Staphylococcus aureus (S. aureus). The deep tissue infections are difficult to treat using topical antibiotics, due to their poor tissue penetration. In order to treat S. aureus deep tissue infections we have developed an antibiotic delivery system using chitosan nanoparticles (CNPs). To enhance their tissue penetration these CNPs were further coated using lecithin (CLNPs). Antibiotic tigecycline was loaded into chitosan nanoparticles (tCNPs) and then coated with lecithin to generate lecithin coated tigecycline loaded chitosan nanoparticles (tCLNPs). The prepared nanoparticles were characterized using DLS, SEM, TEM and FT-IR. The prepared CNPs, tCNPs, CLNPs and tCLNPs have the size range of 85 ± 10, 90 ± 18, 188 ± 5 and 235 ± 20 nm, respectively. The tCLNPs shows more sustained release pattern of tigecycline. The antibacterial activity of the developed nanoparticles was confirmed against laboratory and clinical strains of S. aureus using in vitro and ex vivo experiments. The ex vivo skin and muscle permeation study ensures the enhanced delivery of tigecycline to the deeper tissue. The prepared nanoparticles were hemo-compatible and cyto-compatible. Our study suggests that the prepared tCLNPs can be effectively used for the treatment of S. aureus infected wounds.

Topics: Animals; Cell Line, Tumor; Chitosan; Drug Carriers; Mice; Minocycline; Muscle, Skeletal; Nanoparticles; Staphylococcal Skin Infections; Staphylococcus aureus; Swine; Tigecycline; Wound Infection

Using the US Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate because they are too high to meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline. Revised breakpoints are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates.. The objectives of this study were to measure minimum inhibitory concentrations (MICs) of minocycline and doxycycline of 100 canine meticillin-resistant SP clinical isolates, compare their susceptibilities to minocycline and doxycycline based on current and revised standards, and document their tetracycline resistance genes.. E-test strips were used to determine MICs. PCR was used to identify tet genes.. Using the human tetracycline breakpoint of MIC ≤ 4 μg/mL, 76 isolates were susceptible to minocycline and 36 isolates were susceptible to doxycycline. In contrast, using the proposed minocycline breakpoint (MIC ≤ 0.25 μg/mL) and approved doxycycline breakpoint (MIC ≤ 0.125 μg/mL), 31 isolates were susceptible to both minocycline and doxycycline. Thirty-one isolates carried no tet genes, two had tet(K) and 67 had tet(M).. Use of the human tetracycline breakpoints misclassified 45 and five of the isolates as susceptible to minocycline and doxycycline, respectively. PCR analysis revealed that 43 and five of the isolates classified as susceptible to minocycline and doxycycline, respectively, possessed the tetracycline resistance gene, tet(M), known to confer resistance to both drugs. These results underscore the importance of utilizing the proposed minocycline and approved doxycycline canine breakpoints in place of human tetracycline breakpoints.

Topics: Animals; Anti-Bacterial Agents; Dog Diseases; Dogs; Doxycycline; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Skin Infections; Staphylococcus intermedius

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections

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

Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population pharmacokinetic model and Monte Carlo simulation (9999 patients) were used to create a likelihood distribution of tigecycline exposure, as measured by the area under the concentration-time curve at 24 h (AUC(24)). Each resultant AUC(24) value was paired with a clinically relevant fixed MIC value ranging from 0.12 to 2 mg/L. For each AUC(24)-MIC pair, the probability of microbiologic response was calculated using an exposure-response relationship, which was derived from patients with complicated skin and skin structure infections that involved Staphylococcus aureus or streptococci or both. The median probability of microbiologic success was 94% or greater for MIC values up to and including 0.25 mg/L. The median probability of microbiologic success was 66% or less for MIC values of 0.5 mg/L or greater. These data support a susceptibility breakpoint of 0.25 mg/L for S. aureus and streptococci.

Topics: Anti-Bacterial Agents; Area Under Curve; Computer Simulation; Humans; Microbial Sensitivity Tests; Minocycline; Models, Biological; Models, Statistical; Monte Carlo Method; Regression Analysis; ROC Curve; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Tigecycline

Diagnostic PCR assays were developed to track common genetic determinants of oxacillin resistance as well as resistance to classical tetracyclines in Staphylococcus aureus isolates from the recently completed worldwide phase 3 clinical trials of tigecycline. A total of 503 unique S. aureus strains isolated from complicated skin and skin structure infections were analyzed. The mecA gene was amplified from 120 strains (23.9%) determined to be resistant to oxacillin (MICs > or = 4 microg/ml). The prevalence of the mecA gene was found to vary regionally from 6.5% to 50.9% among isolates originating in Eastern Europe and North America, respectively. The presence of a tetracycline resistance determinant, tet(M) or tet(K), among methicillin-resistant S. aureus (MRSA) isolates also varied regionally, with a range of 11.9% to 46.2% among isolates tested from North America and Eastern Europe, respectively. The occurrence of a tetracycline resistance marker in methicillin-susceptible S. aureus (MSSA) strains varied from 2.5 to 16.1% among the isolates tested across the regions of study. The presence of tet(M) or tet(K) had no discernible effect on the tigecycline MICs for either MRSA or MSSA strains, which is consistent with the ability of the glycylcyclines to retain activity in the presence of both the ribosomal protection and efflux mechanisms of resistance to the tetracyclines.

Topics: Clinical Trials, Phase II as Topic; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Staphylococcal Skin Infections; Staphylococcus aureus; Tetracycline Resistance; Tigecycline

We did a statistical study of 294 strains of Staphylococcus aureus (S. aureus) isolated from skin infections during the period from January of 1989 to December of 1991 in the Department of Dermatology, Kansai Medical University Hospital. We especially examined methicillin-resistant S. aureus (MRSA) from the point of view of incidence, variety of skin infections with MRSA, coagulase type, phase type, and resistance against antimicrobial agents. The frequency of isolation of MRSA has been increasing. In 1991, the proportion of MRSA isolates among all S. aureus strains isolated from skin infections was 41.5%. MRSA was isolated most often from infectious decubitus. Coagulase type II and phage group NT (not typable) MRSA were most frequently isolated. The resistance of MRSA to OFLX and IMP/CS had remarkably increased. Notably, the resistance to MINO was low before 1991.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteriophage Typing; Child; Cilastatin; Coagulase; Colony Count, Microbial; Drug Resistance, Microbial; Humans; Imipenem; Impetigo; Methicillin Resistance; Middle Aged; Minocycline; Ofloxacin; Pressure Ulcer; Staphylococcal Skin Infections; Staphylococcus aureus