minocycline and Streptococcal-Infections

Methicillin-resistant Staphylococcus aureus (MRSA) is a dynamic pathogen. Rates of MRSA are increasing worldwide. In some centers, MRSA is becoming less susceptible to vancomycin, and these strains have been associated with worse clinical outcomes. Intermediate or fully resistant vancomycin strains of MRSA have emerged clinically, whereas MRSA acquired in the community has become epidemic. The purpose of this manuscript is to provide clinicians with an evidence-based review on new treatments for MRSA.. Linezolid, daptomycin and tigecycline have been approved during the last decade to treat infections due to MRSA. Although these agents are extremely valuable in the fight against MRSA, each one has limitations. New lypoglycopeptides (telavancin, dalbavancin and oritavancin) are in advanced phase of clinical development. Similarly, new broad-spectrum cephalosporins active against MRSA (e.g. ceftobiprole and ceftaroline) and a new dihydrofolate reductase inhibitor (iclaprim) are in or have completed phase 3 studies.. Here, we review the most relevant information on new drugs to treat MRSA. New studies with available agents and upcoming studies with investigational drugs will help to better understand the role of each compound in the treatment of patients infected with MRSA and assist the clinician in keeping pace with this challenging pathogen.

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Daptomycin; Evidence-Based Medicine; Glycopeptides; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pyrimidines; Streptococcal Infections; Tigecycline

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

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Bacterial Infections; Bacteroides Infections; Cephalosporins; Drug Hypersensitivity; Haemophilus Infections; Humans; Meningococcal Infections; Minocycline; Penicillin Resistance; Penicillins; Streptococcal Infections; Typhoid Fever

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

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

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

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

Scarce data are available on Group A Streptococcus (GAS) antibiotic resistance in South America.. The antibiotic susceptibility patterns of GAS recovered from symptomatic children living in the central part of Brazil during a prospective epidemiological study were analyzed.. No isolates were resistant to penicillin or macrolides.  Sixty-one percent of the isolates were highly resistant to tetracycline, of which 85% harboured the tetM resistance gene. Ninety-five percent of these tetracycline resistant isolates were also resistant to minocycline. Thirty different emm-types were associated with tetracycline resistance. Phylogenetic analysis indicates that tetracycline resistance arose independently in distantly related emm-types.. A high level of GAS tetracycline resistance has been observed in the central part of Brazil due to the polyclonal dissemination of resistant emm-types.

Topics: Adolescent; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Brazil; Carrier Proteins; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Macrolides; Microbial Sensitivity Tests; Minocycline; Penicillins; Phylogeny; Streptococcal Infections; Streptococcus pyogenes; Tetracycline Resistance

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

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

Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis.. Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05). The optical density ratio (Odr) decreased significantly at 2x MIC for tigecycline, and at 8x MIC for linezolid and vancomycin (p<0.05). Although biofilms persisted even at the highest antibiotic concentrations of 128x MIC, bacterial growth was eradicated starting at concentrations of 16x MIC for vancomycin and of 32x MIC for linezolid, but not for tigecycline, up to a concentration of 128x MIC.. In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.

Topics: Acetamides; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biofilms; Dose-Response Relationship, Drug; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Oxazolidinones; Prosthesis-Related Infections; Streptococcal Infections; Tigecycline; Treatment Outcome; Vancomycin; Viridans Streptococci

Topics: Anti-Bacterial Agents; Cross Infection; Denmark; Drug Resistance, Bacterial; Genes, Bacterial; Genotype; Humans; Minocycline; Streptococcal Infections; Streptococcus pyogenes; Tetracycline

In the present study 79 streptococcal cultures isolated from subclinical mastitis of 54 cows from seven dairy farms (A-G) in Hesse, Germany, were comparatively investigated using conventional and molecular methods. The isolates could be identified as Streptococcus agalactiae, belonging to Lancefield's serological group B by determination of cultural, biochemical and serological properties and by polymerase chain reaction (PCR)-mediated amplification of species-specific parts of the 16S ribosomal DNA, the 16S-23S rDNA intergenic spacer region and the CAMP factor gene cfb. The investigated group B streptococci were further characterized serologically for specific polysaccharide and protein antigens. Serotyping the isolates revealed a predominance of surface protein antigen X, either alone or in combination with polysaccharide antigen Ia. This could be observed for 39 isolates of farms A, B and C. Six group B streptococci from farm E displayed the serotype pattern III/Rib, two isolates from farm G showed the serotype pattern Ib/calpha. The remaining cultures from farms D and F (n=32) were non-typable. The occurrence of protein Rib could be confirmed by PCR amplification of the gene rib. The two isolates with serotype pattern Ib/calpha also reacted positively for the cbeta-encoding gene bag. Additional properties which allowed a phenotypic characterization of the S. agalactiae were the degree of pigmentation, growth properties in fluid media and soft agar, the surface hydrophobicity, the ability to hemagglutinate rabbit erythrocytes and their resistance reactions to tetracycline and minocycline. The isolates of the seven farms showed identical or almost identical characteristics. The 79 group B streptococci were additionally investigated by macrorestriction analysis of their chromosomal DNA using the restriction endonucleases SmaI, ApaI and SalI. The restriction patterns obtained by pulsed-field gel electrophoresis displayed identical or closely related patterns for the cultures of the various farms. The pheno- and genotypic characteristics of the 79 group B streptococci of the present study revealed that a single S. agalactiae strain or at least closely related subtypes of this strain were responsible for the mastitis situation of the seven farms.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Bacterial Typing Techniques; Cattle; Chromosomes, Bacterial; Culture Media; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Germany; Hemagglutination; Mastitis, Bovine; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Serotyping; Streptococcal Infections; Streptococcus agalactiae; Tetracycline

Clinical blood isolates from three sequential episodes of endocarditis occurring over a 6-month period in a child with a malformative cardiopathy were investigated. All isolates identified as Abiotrophia defectiva were resistant to erythromycin-clindamycin and to tetracycline-minocycline, due to the presence of sequences homologous to the erythromycin resistance gene ermB and to the tetracycline resistance gene tet(M), respectively. These resistance genes were located on a chromosomally borne composite Tn916-related transposon. These results demonstrate the involvement of conjugative transposons in the dissemination of antibiotic resistance in the genus Abiotrophia.

Topics: Anti-Bacterial Agents; Blotting, Southern; Child, Preschool; Clindamycin; DNA Transposable Elements; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; Endocarditis, Bacterial; Erythromycin; Humans; Male; Methyltransferases; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Streptococcal Infections; Streptococcus; Tetracycline Resistance

We isolated 73 streptococcus strains (41 from infections, and 32 from colonization) from various skin diseases between March, 1994, and June, 1998. In 29 out of 41 cases of infective origin, Staphylococcus aureus strains were simultaneously isolated. Twenty-four out of 28 patients with impetigo were suffering from atopic dermatitis. We confirmed that impetigo lesions where Streptococcus pyogenes was dominant in number always showed thick-walled pustules on an erythematous base; these skin lesions were considered to be an early manifestation of streptococcal impetigo. We further confirmed that thick-crusted lesions in streptococcal impetigo, where S. aureus exceeded S. pyogenes in number, were a late manifestation. Antimicrobial agents such as minocycline, fusidic acid, ofloxacin and tosufloxacin, were more effective against S. aureus strains than against beta-hemolytic streptococcal strains. In contrast, ampicillin, cefdinir, imipenem, erythromycin and vancomycin were more effective against beta-hemolytic streptococcal strains.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Erythromycin; Fluoroquinolones; Fusidic Acid; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Ofloxacin; Penicillins; Skin Diseases, Bacterial; Species Specificity; Streptococcal Infections; Streptococcus; Vancomycin

Although the precise pathoetiology of Behçet's disease (BD) remains obscure, patients with BD have a high incidence of chronic infectious foci, indicating an enhanced susceptibility to chronic tonsillitis, and dental caries. Sometimes, clinical symptoms appear after treatment of these foci in BD patients. It is believed that BD might be related to an allergic reaction to a bacterial infection in view of the many clinical symptoms, especially the presence of aphthous and genital ulcerations. An attempt to obtain cutaneous responses to bacterial antigens has been carried out using various vaccines developed from bacteria isolated from the ulcerative lesions and oral cavities of BD patients. BD patients often show intense hypersensitivity to various strains of streptococci, not only by their cutaneous reactions but also by in vitro testing. In this report, we describe our previous studies on the correlation between streptococcal antigens and the pathogenesis of BD and also discuss the recent reports of other authors. The intense hypersensitivity to streptococcal antigens acquired after streptococcal infection is thought to play an important role in the appearance of symptoms in BD patients since the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) was enhanced when stimulated with streptococcal antigen in a culture system. Minocycline, an antibiotic to which certain strains of streptococci are sensitive, reduced the frequency of clinical symptoms in BD patients as well as the production of pro-inflammatory cytokines by BD-PBMC stimulated with streptococcal antigen.

Topics: Adult; Anti-Bacterial Agents; Antigens, Bacterial; Behcet Syndrome; Cytokines; Female; Humans; Male; Minocycline; Skin Tests; Streptococcal Infections

Serotyping of 50 streptococcal strains of serological group B isolated from human clinical specimens in Chile revealed mainly the serotypes Ia, II and III, either alone or in combination with protein antigens c or R. No significant difference in serotype distribution was detected between group B streptococci isolated from cervical swabs from clinically healthy women and those isolated from various pathological processes. Determination of antibiotic susceptibility of the bacteria demonstrated resistance to tetracycline and minocycline in 29 isolates. All 29 tetracycline-resistant cultures hybridised with a gene probe for tet(M). Again, no differences were detected between the group B streptococcal isolates of various origins.

Topics: Blotting, Southern; Carrier State; Cervix Uteri; Chile; DNA Probes; DNA, Bacterial; Drug Resistance, Microbial; Female; Genes, Bacterial; Humans; Infant, Newborn; Minocycline; R Factors; Serotyping; Streptococcal Infections; Streptococcus agalactiae; Tetracycline Resistance

A case of prolonged infection of the floor of the mouth with a generalized eczematous dermatitis in a 13-year-old boy is described. Immunologic examination revealed markedly elevated serum concentration of immunoglobulin E (IgE) and impaired neutrophil chemotaxis. The disorder was diagnosed as the hyperimmunoglobulinemia E (Buckley's syndrome) and was successfully treated with high doses of antibiotics and human immunoglobulin.

Topics: Adolescent; Chemotaxis, Leukocyte; Humans; Immunoglobulin E; Job Syndrome; Male; Minocycline; Mouth Floor; Neutrophils; Periapical Abscess; Skin Diseases, Eczematous; Streptococcal Infections

Seventy-one streptococci isolated from dairy cows with clinical mastitis were tested for tetracycline resistance. Twenty-one (30%) isolates were tetracycline resistant (Tcr), and eight hybridized with the Tet O, one hybridized with the Tet L, and one hybridized with both the Tet L and Tet K determinants. The remaining Tcr isolates did not hybridize with any of the 5 Gram-positive Tet determinants tested. The Tet O determinants were plasmid-mediated, and four selected strains transferred the Tet O determinant at frequencies of 10(-6) to 10(-8). Strains which did not hybridize with known probes were tested for resistance to minocycline. All of the Streptococcus dysgalactiae had low minimum inhibitory concentrations (MICs) for minocycline, while the S. agalactiae and the one S. uberis showed high MICs to minocycline. This suggests that at least two different uncharacterized Tet determinants exist in these isolates, one conferring high resistance to both tetracycline and minocycline and one conferring only tetracycline resistance.

Topics: Animals; Cattle; DNA Probes; DNA, Bacterial; Female; Mastitis, Bovine; Minocycline; Nucleic Acid Hybridization; Streptococcal Infections; Streptococcus; Streptococcus agalactiae; Tetracycline Resistance

Topics: Adult; Aged; Ampicillin; Cephalosporins; Child; Chloramphenicol; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Female; Gastrointestinal Diseases; Gentamicins; Humans; Kanamycin; Lincomycin; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Oxacillin; Penicillin G; Streptococcal Infections; Streptococcus; Streptomycin; Tetracycline; Urologic Diseases; Vancomycin

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