minocycline and Respiratory-Tract-Infections

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

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

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

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

Tigecycline is indicated for the treatment of complicated skin infections, soft tissue and intraabdominal infections. Its use could be extended to community-acquired pneumonia (CAP) and hospital pneumonia (HN). The objective was to evaluate the efficacy and safety of tigecycline in the treatment of respiratory infections.. systematic review (2012). Databases used were MEDLINE, EMBASE, Cochrane Library, CRD and WOK. We identified clinical trials of adults with respiratory infection, treated with tigecycline. The quality of the studies was assessed using CASPe checklist.. We selected four clinical trials of high-moderate quality. Three studies with patients with CAP and a trial with HN patients. In patients with CAP, efficacy of tigecycline (88.6 to 90.6%) was higher than levofloxacin (85.3 to 87.2%). The non inferiority testing was statistically significant (p < 0.001). In the study of patients with HN tigecycline showed an efficiency of 67.9% versus 78.2% for imipenem/cilastatin. Main adverse effects were gastrointestinal.. The efficacy of tigecycline is non inferior than levofloxacin in patients with CAP, but less than imipenem in patients with HN. Tigecycline demonstrates noninferiority versus others tested antibiotics, and it shows a good safety profile.

Topics: Adult; Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Cross Infection; Humans; Minocycline; Pneumonia; Respiratory Tract Infections; Tigecycline

Mycobacterium abscessus is the most pathogenic and chemotherapy-resistant rapid-growing mycobacterium. It is commonly associated with contaminated traumatic skin wounds and with post-surgical soft tissue infections. It is also one of the mycobacteria that are most often isolated from cystic fibrosis patients. It is essential to differentiate this species from the formerly indistinct "M. chelonae-complex", as chemotherapy is especially difficult in M. abscessussenso strictu. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents with an effect on M. abscessus, and should preferably be supplemented with other drugs since long-term monotherapy may cause resistance. Amikacin is a major parenteral drug against M. abscessus that should also be given in combination with another drug. The recently introduced drug tigecycline may prove to be an important addition to chemotherapy, but has yet to be fully clinically evaluated as an antimycobacterial agent. Surgery can be curative, or at least helpful, in the healing of M. abscessus infection, and if conducted, it should include the removal of all foreign or necrotic material. There is increasing awareness of M. abscessus as an emerging pathogen.

Topics: Administration, Oral; Amikacin; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Mycobacterium; Mycobacterium Infections; Respiratory Tract Infections; Skin; Soft Tissue Infections; Species Specificity; Surgical Wound Infection; Tigecycline; Tuberculosis, Cutaneous; Wounds and Injuries

A 24-year-old woman had been treated with minocycline (MINO) for acute upper airway infection. Two days after the start of MINO therapy, she developed fever, cough, dyspnea, and bloody sputum. Her chest X-ray film revealed bilateral pleural effusions and butterfly shadow, and chest computed tomography revealed markedly increased density of pulmonary tissue in the central lung fields. Arterial blood gas analysis demonstrated severe hypoxemia. The characteristics of the pleural effusion were exudative. Based on the history of her illness and the chest X-ray findings, in addition to the laboratory findings of leukocytosis with eosinophilia and increased serum IgE, drug-induced pneumonia was suspected. Once the treatment with MINO was discontinued, her symptoms, laboratory data, and chest X-ray findings improved rapidly. Microscopic examination of a transbronchial lung biopsy specimen showed increased alveolar septal thickness with formation of Masson's bodies. Although the result of a lymphocyte stimulation test was negative for MINO, the skin test was positive for immediate response. Because of her clinical course, the possibility of induction by other drugs was excluded. This patient was therefore diagnosed to have MINO-induced pneumonia. To date, ten cases of MINO-induced pneumonia have been reported, but no previous case was associated with pleurisy.

Topics: Acute Disease; Adult; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Female; Humans; Minocycline; Pleurisy; Pneumonia; Respiratory Tract Infections; Tomography, X-Ray Computed

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

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

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

Infection of the upper respiratory tract is one of the most common causes of olfactory loss. One of the possible underlying pathologic pathways is an increase of apoptosis of olfactory receptor neurons. Therefore, treatment with the antibiotic minocycline, which has been shown to act as an antiapoptotic agent, is thought to accelerate improvement of olfactory function. To investigate this idea, 55 patients with postinfectious olfactory dysfunction were tested for their olfactory ability.. Randomized, prospective, double-blind, placebo-controlled.. Olfactory function was examined by means of a standardized psychophysical method (Sniffin' Sticks) before and 7 months after a 3-week treatment with either minocycline (2 × 50 mg/d) or a placebo.. Statistical analyses did not reveal any influence of the treatment on the progress of olfactory function, possibly indicating that pathologic changes other than apoptosis contribute to postinfectious olfactory loss, either on a peripheral level (e.g., scarring/reorganization of the olfactory epithelium) or on a central nervous level.. In conclusion, the present results indicate that minocycline in the given dosage has little or no effect on the recovery of human olfactory function following postinfectious olfactory loss. However, spontaneous recovery is found in approximately 20% of the patients over an observation period of 7 months.

Topics: Administration, Oral; Anti-Bacterial Agents; Apoptosis; Double-Blind Method; Female; Humans; Male; Middle Aged; Minocycline; Olfaction Disorders; Olfactory Receptor Neurons; Prospective Studies; Remission, Spontaneous; Respiratory Tract Infections; Sensory Thresholds; Smell

Topics: Child; Dosage Forms; Humans; Minocycline; Otorhinolaryngologic Diseases; Respiratory Tract Infections; Skin Diseases, Infectious; Tablets; Tetracyclines

Topics: Adult; Clinical Trials as Topic; Drug Resistance, Microbial; Haemophilus; Humans; Minocycline; Respiratory Tract Infections; Streptococcus pneumoniae; Tetracycline; Tetracyclines; Time Factors

Doxycycline and minocycline were given intravenously to patients with a serious underlying disease who presented a pulmonary infection or a wound infection. Both therapies were easy to administer and well tolerated. However they should not be used in the initial therapy since resistant strains may occur. The clinical and bacteriological effectiveness of doxycycline and minocycline were similar. In pneumococcal pulmonary infections, the rates of favorable clinical response to doxycycline and minocycline were 73% and 76% respectively. In infections caused by bacteroides sp.(mainly infections of wounds), doxycycline or minocycline resulted in a 75% rate of favorable clinical responses and in a 71% rate of favorable bacteriological responses. Adverse side effects were rare and of minor importance with the exception of bacteriological colonization by doxycycline-resistant or minocycline-resistant microorganisms. This complica-tion occurred in 39% of the patients who were treated with these drugs and resulted in clinical superinfection in 8% of the patients.

Topics: Adult; Aged; Clinical Trials as Topic; Doxycycline; Drug Evaluation; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Surgical Wound Infection; Tetracyclines

Topics: Administration, Oral; Bacterial Infections; Clinical Trials as Topic; Female; Humans; Injections, Intravenous; Male; Minocycline; Respiratory Tract Infections; Skin Diseases, Infectious; Tetracycline; Urinary Tract Infections

Infections due to multidrug- and extensively drug-resistant forms of. Enrolled were patients with MDR-AB or XDR-AB pulmonary infection based on their first sputum culture. Patients were treated empirically with carbapenems (n = 46), tigecycline (n = 25), or cefoperazone/sulbactam (cefina-SB; n = 35). The therapeutic efficacies of the drugs and patient outcomes were retrospectively compared. Bacterial resistance to the three antibacterials was determined based on sputum cultures from all enrolled patients.. The study included 106 patients. After 7 days of treatment, the favorable response rates to tigecycline (60%) and to cefina-SB (71.4%) were statistically similar (p = 0.355) but significantly higher than that to carbapenems (23.9%; p = 0.003 and p < 0.001, respectively). Sputum culture analyses to determine antibiotic susceptibility indicated that 10.4% of patients' sputum cultures were susceptible to carbapenems, 76.4% to tigecycline, and 66.0% to cefina-SB. In addition, 58.5% were susceptible to both tigecycline and cefina-SB.. Tigecycline and cefina-SB appeared to be more effective against MDR-AB and XDR-AB pulmonary infections than carbapenems, especially for patients who had been admitted to the intensive care unit multiple times.
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Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Cefoperazone; China; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Hospitals, Teaching; Humans; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Retrospective Studies; Sputum; Sulbactam; Tigecycline; Time Factors; Treatment Outcome

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

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

Bordetella bronchiseptica is a bacterial pathogen usually isolated from animals and rarely causes human infections. There are, however, some reports that B. bronchiseptica causes human respiratory infections in immunocompromised patients or those with underlying respiratory diseases, although there is a lack of treatment guidelines. An 80-year-old woman was admitted to our hospital to treat anti-neutrophil cytoplasmic antibodies-associated vasculitis. On the 16th day after admission, she complained of a productive cough with right pleuritic pain and had low-grade fever. After chest CT scans, we diagnosed pneumonia. Gram stain of her sputum revealed moderate levels of gram-negative coccobacilli, which was later identified as B. bronchiseptica by mass spectrometry. According to the result of minimum inhibitory concentration, we successfully treated the pneumonia with minocycline. This case suggests that B. bronchiseptica pneumonia can be treated by minocycline if the minimum inhibitory concentration is less than 0.25 μg/mL.

Topics: Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Bordetella bronchiseptica; Bordetella Infections; Female; Humans; Minocycline; Pneumonia; Respiratory Tract Infections; Vasculitis

Fifty-three Mycoplasma pneumoniae strains were isolated from pediatric patients in Shanghai, China, from October 2005 to February 2008. Of 53 clinical isolates, 44 (83%) were resistant to erythromycin (MICs of >128 microg/ml for all 44 strains), azithromycin, and clarithromycin. All macrolide-resistant M. pneumoniae strains harbored an A-to-G transition mutation at position 2063 in 23S rRNA genes. Forty-five (85%) clinical isolates were classified into the P1 gene restriction fragment length polymorphism type I, and six (11%) were type II.

Topics: Adhesins, Bacterial; Anti-Bacterial Agents; Child; China; Drug Resistance, Bacterial; Genes, rRNA; Humans; Macrolides; Microbial Sensitivity Tests; Mutation; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Respiratory Tract Infections; RNA, Ribosomal, 23S; Sequence Analysis, DNA

Tigecycline (TGC), a semisynthetic glycylcycline, has a documented activity on Gram+ and Gram- pathogens including oxacillin-resistant (MRSA) and an extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Tigecycline Evaluation and Surveillance Trial (TEST) is an international surveillance study designed to assess the in vitro activity of TGC and 11 comparators against a range of important clinical pathogens from both the community and the hospital. The aim of this study was to assess efficacy of TGC, using this database, against pathogens implicated in community or hospital pneumonia and sinusitis. A total of 4163 isolates were consecutively collected in 21 European countries during three years (2004-2007). In all center, minimum inhibitory concentration (MIC) were determinated with the same Microscan panel (Dade-Behring). Tigecycline exhibited a good activity against respiratory pathogens, with the exception of Pseudomonas aeruginosa. Hundred percent of cocci Gram+ (Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus sp.) and 100% of Haemophilus sp. are inhibited with 0.5 mg/L, without effect of an associated beta-lactam resistance mechanism. TGC is active in vitro on 89% of Enterobacteriaceae, with MIC 90 less or equal to 2mg/L. Eighty-nine percent of Enterobacter sp. and 77% of Serratia sp. are susceptible with range of MIC 90 from 2 to 4 mg/L. These interesting results obtained in vitro are to be strengthened by clinical studies.

Topics: Bacteria; Bacterial Infections; Bronchoalveolar Lavage Fluid; Drug Evaluation; Drug Resistance, Microbial; Enterobacteriaceae; Europe; Haemophilus; Humans; In Vitro Techniques; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Respiratory Tract Infections; Species Specificity; Streptococcus pneumoniae; Tigecycline

Topics: Ampicillin Resistance; Anti-Bacterial Agents; Community-Acquired Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Tigecycline

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Female; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Respiratory Tract Infections; Sensitivity and Specificity; Skin Diseases, Infectious; Tigecycline; United States

A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being penicillin resistant (MIC, > or =2 microg/ml). The proportion of high-level penicillin-resistant S. pneumoniae isolates increased from 2.4 to 13.8% over the last 3 years of the study, and the proportion of multidrug-resistant S. pneumoniae isolates increased from 2.7 to 8.8% over the 5-year period. Resistant rates (intermediate and resistant) among non-beta-lactam agents were as follows: macrolides, 9.6 to 9.9%; clindamycin, 3.8%; doxycycline, 5.5%; chloramphenicol, 3.9%; and trimethoprim-sulfamethoxazole, 19.0%. Rates of resistance to non-beta-lactam agents were higher among penicillin-resistant strains than among penicillin-susceptible strains. No resistance to vancomycin or linezolid was observed; however, 0.1% intermediate resistance to quinupristin-dalfopristin was observed. The rate of macrolide resistance (intermediate and resistant) increased from 7.9 to 11.1% over the 5 years. For the fluoroquinolones, the order of activity based on the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s was gemifloxacin > clinafloxacin > trovafloxacin > moxifloxacin > grepafloxacin > gatifloxacin > levofloxacin > ciprofloxacin. The investigational compounds ABT-773 (MIC(90), 0.008 microg/ml), ABT-492 (MIC(90), 0.015 microg/ml), GAR-936 (tigecycline; MIC(90), 0.06 microg/ml), and BMS284756 (garenoxacin; MIC(90), 0.06 micro g/ml) displayed excellent activities. Despite decreases in the rates of antibiotic consumption in Canada over the 5-year period, the rates of both high-level penicillin-resistant and multidrug-resistant S. pneumoniae isolates are increasing in Canada.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Canada; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fluoroquinolones; Humans; Indoles; Ketolides; Longitudinal Studies; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumococcal Infections; Quinolones; Respiratory Tract Infections; Streptococcus pneumoniae; Tigecycline

A total of 7,566 unique patient isolates of Haemophilus influenzae and 2,314 unique patient isolates of Moraxella catarrhalis were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among the 7,566 H. influenzae isolates, 22.5% produced beta-lactamase, while 92.4% of the 2,314 M. catarrhalis isolates produced beta-lactamase. The incidence of beta-lactamase-producing H. influenzae isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (P < 0.01). The incidence of beta-lactamase-producing M. catarrhalis isolates did not change over the study period. The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for H. influenzae were 19.3 and 0.1%, respectively. The rank order of cephalosporin activity based on the MICs at which 90% of isolates were inhibited (MIC(90)s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor. On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively. Rates of resistance to other agents were as follows: doxycycline, 1.5%; trimethoprim-sulfamethoxazole, 14.2%; and chloramphenicol, 0.2%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against H. influenzae, with MIC(90)s of < or = 0.03 microg/ml. The MIC(90)s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 microg/ml, respectively, and the MIC(90) of the investigational glycylcycline GAR-936 (tigecycline) was 4 microg/ml. Among the M. catarrhalis isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for H. influenzae were <1% for all antibiotics tested except trimethoprim-sulfamethoxazole (1.5%). In summary, the incidence of beta-lactamase-positive H. influenzae strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of beta-lactamase-positive M. catarrhalis strains has remained constant (90.0% in 2001-2002).

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Canada; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Gram-Negative Bacterial Infections; Haemophilus influenzae; Humans; Influenza, Human; Ketolides; Longitudinal Studies; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Moraxella catarrhalis; Respiratory Tract Infections; Tigecycline

We report two cases of acute pancreatitis secondary to minocycline use in adults with cystic fibrosis (CF). This minocycline complication has not previously been reported. Given the increased use of minocycline in the adult CF population to treat resistant bacteria, awareness of this potential adverse effect is imperative. As both of these individuals with CF had class IV genotypes and pancreatic sufficiency, close observation is warranted in the future to determine if persons with pancreatic-sufficient CF are at an increased risk for minocycline-induced pancreatitis.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Cystic Fibrosis; Female; Humans; Minocycline; Pancreatitis; Respiratory Tract Infections

Our objective was to determine the in vitro activity of minocycline against isolates of Burkholderia cepacia (BC), Stenotrophomonas maltophilia (SM), and Pseudomonas aeruginosa (PA) cultured from the respiratory tract of patients with cystic fibrosis (CF). Cultures of BC, SM, and PA were isolated in a hospital bacteriology laboratory from the sputum or oropharyngeal cultures obtained from patients attending a Cystic Fibrosis Center, and were prospectively tested for in vitro sensitivity to minocycline by Kirby-Bauer disk diffusion. From January 1994 to July 1995, 116 cultures from 61 patients had at least one of the three pathogens; 9/61 (15%) patients had an isolate of BC, and 7/9 (78%) had an initial isolate sensitive to minocycline, of which 3 were sensitive only to minocycline; 2 cultures were resistant to all antibiotics. Four of 7 patients with BC were treated with minocycline; 3 patients developed resistant isolates 3-13 months after therapy. Five of 61 patients (8%) had an isolate of SM: 4/5 (80%) of these isolates were sensitive to minocycline, of which 1 was sensitive only to minocycline. Fifty-five of 61 patients (90%) had at least one PA isolate, with 112 morphotypes recovered from 90 cultures: 40/112 morphotypes (36%) were sensitive to minocycline, 65 (58%) were resistant, and 7 (6%) were intermediate in sensitivity. We conclude that the marked in vitro activity of minocycline against BC and SM isolated from patients with CF suggests that minocycline may have an adjunct role in the antimicrobial therapy of multidrug resistant, respiratory pathogens in CF.

Topics: Adolescent; Anti-Bacterial Agents; Burkholderia cepacia; Burkholderia Infections; Child; Child, Preschool; Cystic Fibrosis; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Oropharynx; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sputum; Stenotrophomonas maltophilia; Tetracycline Resistance

One hundred and thirteen strains of Streptococcus pneumoniae (S. pneumoniae) were isolated from the clinical specimens of patients with respiratory tract infections between January and December 1998 in three hospitals in Hokusetsu area of Osaka. We investigated susceptibility of 113 strains of S. pneumoniae to benzylpenicillin (PCG) and other antimicrobial agents and their serotypes. 1) Of the 113 strains of S. pneumoniae isolated, 25.7% were susceptible (PSSP), 51.3% were intermediate (PISP) and 23% were resistant to benzylpenicillin (PRSP). 2) The MICs of cefaclor, cefditoren, cefpodoxime, cefdinir, erythromycin, clindamycin and minocycline were elevated, but the MIC values of cefditoren ranged from < or = 0.03 to 1.0 microgram/ml. The susceptibility of 113 strains to cefditoren was comparatively high. 3) The MIC values of imipenem, meropenem and vancomycin for 81 strains of PISP and PRSP ranged from < or = 0.015 to 1.0 microgram/ml, from < or = 0.015 to 2.0 micrograms/ml and from 0.13 to 0.5 microgram/ml, respectively. The susceptibility of these strains to three antimicrobial agents was superior to that to the other antimicrobial agents examined. 4) Of the 60 strains examined, 19, 6, and 23 serotypes were 30, 25 and 18.3%, respectively. The three serotypes were observed in PISP and PRSP with a high frequency. 5) Isolates of S. pneumoniae were 37.2% for children under 2 years of age and 30.9% for children from 2 to 6 years of age. Most of the strains isolated from these children were resistant.

Topics: Anti-Bacterial Agents; Cefdinir; Cefpodoxime; Ceftizoxime; Cephalosporins; Child; Child, Preschool; Clindamycin; Erythromycin; Humans; Minocycline; Penicillin G; Penicillins; Respiratory Tract Infections; Serotyping; Streptococcus pneumoniae

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

Topics: Aged; Aged, 80 and over; Aging; Anti-Bacterial Agents; Bacterial Infections; Body Weight; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Humans; Male; Minocycline; Respiratory Tract Infections; Statistics as Topic; Time Factors

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

Using pharyngeal epithelial cells from a healthy adult and eight strains of Branhamella catarrhalis (B. catarrhalis) isolated from eight patients with respiratory infection the effect of subminimal inhibitory concentrations of cefmetazole, ampicillin and minocycline on adherence was examined. Cefmetazole-treated bacterial attachment (44 +/- 28; mean +/- S.D.) decreased significantly (p less than 0.05) compared to the control (84 +/- 27). Statistically no significant difference in adherence was found between ampicillin-treated bacteria (63 +/- 36) and the control (95 +/- 40) or minocycline-treated bacteria (91 +/- 39) and the control (109 +/- 40). Large bacteria was observed after cefmetazole and ampicillin treatment. In addition to diplococci, tetrads were observed after cefmetazole treatment. Significant correlation between the MICs and adherence ability was not found. The results suggests that these three antibiotics were not responsible for the increase in B. catarrhalis infection by increasing adherence ability.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Infections; Cefmetazole; Epithelium; Humans; In Vitro Techniques; Minocycline; Moraxella catarrhalis; Pharynx; Respiratory Tract Infections

The minimal inhibitory concentrations (MIC) of five tetracyclines and ten other antimicrobial agents were determined for four porcine bacterial respiratory tract pathogens by the agar dilution method. For the following oxytetracycline-susceptible strains, the MIC50 ranges of the tetracyclines were: P. multocida (n = 17) 0.25-0.5 micrograms/ml; B. bronchiseptica (n = 20) 0.25-1.0 micrograms/ml; H. pleuropneumoniae (n = 20) 0.25-0.5 micrograms/ml; S. suis Type 2 (n = 20) 0.06-0.25 micrograms/ml. For 19 oxytetracycline-resistant P. multocida strains the MIC50 of the tetracyclines varied from 64 micrograms/ml for oxytetracycline to 0.5 micrograms/ml for minocycline. Strikingly, minocycline showed no cross-resistance with oxytetracycline, tetracycline, chlortetracycline and doxycycline in P. multocida and in H. pleuropneumoniae. Moreover, in susceptible strains minocycline showed the highest in vitro activity followed by doxycycline. Low MIC50 values were observed for chloramphenicol, ampicillin, flumequine, ofloxacin and ciprofloxacin against P. multocida and H. pleuropneumoniae. B. bronchiseptica was moderately susceptible or resistant to these compounds. As expected tiamulin, lincomycin, tylosin and spiramycin were not active against H. pleuropneumoniae. Except for flumequine, the MIC50 values of nine antimicrobial agents were low for S. suis Type 2. Six strains of this species showed resistance to the macrolides and lincomycin.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bordetella; Chlortetracycline; Doxycycline; Haemophilus; Microbial Sensitivity Tests; Minocycline; Oxytetracycline; Pasteurella; Respiratory Tract Infections; Streptococcus; Swine; Swine Diseases; Tetracycline; Tetracyclines

A patient with the acquired immunodeficiency syndrome (AIDS) presented with Pneumocystis carinii pneumonia and pulmonary nocardiosis. The nocardial lesions appeared small and localized on chest radiograph. On two separate occasions, nocardial organisms were absent in transbronchial lung biopsy specimens, but were identified in bronchoalveolar lavage fluid probably because the latter specimen sampled a larger area of lung. The patient was initially treated with trimethoprim-sulfamethoxazole (TMP/SMX) for both infections. When TMP/SMX was discontinued because of an adverse reaction, the nocardiosis promptly exacerbated but was then easily controlled with minocycline and amikacin followed by minocycline and cycloserine. Among patients with AIDS who have sulfamethoxazole hypersensitivity during treatment for nocardiosis, alternative drugs may be efficacious and may be particularly important in this setting because they have a lower incidence of toxicity.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amikacin; Cycloserine; Drug Therapy, Combination; Humans; Male; Minocycline; Nocardia asteroides; Nocardia Infections; Pneumonia, Pneumocystis; Pulmonary Alveoli; Radiography; Respiratory Tract Infections; Therapeutic Irrigation

Topics: Bacteria; Barbiturates; Ceftriaxone; Craniocerebral Trauma; Critical Care; Female; Humans; Male; Minocycline; Respiratory Tract Infections; Tetracyclines

Topics: Administration, Oral; Adolescent; Adult; Drug Evaluation; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Minocycline; Renal Dialysis; Respiratory Tract Infections; Tetracyclines; Urinary Tract Infections

Topics: Ampicillin; Female; Humans; Male; Minocycline; Respiratory Tract Infections; Tetracyclines

Minocycline concentrations in serum, saliva, sputum, pleural exudate and lung extracts after a single dose of 0.2 g (orally or intravenously) were measured on 32 patients with bronchial or lung disease. On the first day of treatment, concentrations in purulent sputum were five to ten times higher than in mucous sputum and saliva, after two hours they were one third, after three hours half the serum concentration (0.7 and 1.0 microgram/ml, respectively). After six hours the concentration was the same (1.6 microgram/ml). On the third day of treatment (after 0.2 g every 24 hours) concentrations in purulent sputum were higher than on the first day by 0.8 microgram/ml (after two hours) and by 0.95 microgram/ml (after three hours). After one-hour i.v. infusion of 0.2 g minocycline concentrations in mucous sputum and saliva rose more quickly on the first day than after oral administration. On the third day of treatment (after 0.1 g orally every 12 hours) pleural exudate level was almost as high as serum level. Minocycline concentration in lung extract on the third day of treatment--four, five and ten hours after the last dose--was 0.4 and 0.8 microgram/g, respectively (while serum concentration at the same time was 1.0-1.5 microgram/ml).

Topics: Humans; Lung; Minocycline; Pleural Effusion; Respiratory Tract Infections; Saliva; Sputum; Tetracyclines; Time Factors

Topics: Adolescent; Adult; Aged; Child; Cochlea; Female; Humans; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Tetracyclines; Vestibule, Labyrinth

24 patients with severe infections were treated with intravenous minocycline 100 mg every 12 hours. Average blood levels were within therapeutic ranges during the first 12 hours after the initial dose. Determination of efficacy of therapy in 23 of the patients who were evaluable showed that clinical and bacteriological results were satisfactory in 20 patients, unsatisfactory in 2, and questionable in 1. One patient developed a fatal secondary infection which may have been related to prior therapy with minocycline. No toxicities or side-effects were observed.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cellulitis; Humans; Injections, Intravenous; Middle Aged; Minocycline; Respiratory Tract Infections; Tetracyclines; Urinary Tract Infections

Topics: Aged; Albumins; Bronchial Diseases; Female; Humans; Lung Diseases; Male; Middle Aged; Minocycline; Oxytetracycline; Respiratory Tract Infections; Sputum; Tetracyclines; Time Factors; Transferrin

Topics: Child; Child, Preschool; Female; Humans; Infant; Male; Minocycline; Respiratory Tract Infections; Tetracyclines

The role played by Mycoplasma pneumoniae and possibly by other species of mycoplasma in respiratory tract infections in man is considered. The in vitro sensitivity of human mycoplasmas, that is, M. hominis, M. fermentans, M. orale type 1, M. pneumoniae, M. salivarium and T-mycoplasmas to different tetracycline analogues and some other antibiotics was determined. The strains tested were often somewhat more susceptible to doxycycline than to methacycline, minocycline and tetracycline, while oxytetracycline, per unit of weight, was in most instances 8-16 times less effective than doxycycline. The difference between the minimum concentrations of the above-mentioned tetracyclines, that inhibited metabolism of M. pneumoniae in liquid medium, and the minimum lethal concentrations of these antibiotics was small. Variation of the inoculum size of this organism had comparatively little effect on the result of the susceptibility tests with doxycycline. The study indicates a cidal rather than static action of doxycycline on M. pneumoniae. This organism as well as T-mycoplasmas were sensitive to low concentrations of erythromycin, while the strains of the other species studied were resistant to even 100 mug/ml of this antibiotic. M. pneumoniae and T-mycoplasmas were resistant to 20-80 mg/ml lincomycin, while the other human mycoplasmas were moderately sensitive. Chloramphenicol and gentamycin were generally less effective, per unit of weight, than the tetracyclines against most of the strains of mycoplasma tested. Some known effects of antibiotic treatment of mycoplasma infections in man are also discussed.

Topics: Anti-Bacterial Agents; Chloramphenicol; Doxycycline; Drug Resistance, Microbial; Erythromycin; Gentamicins; Humans; Lincomycin; Methacycline; Microbial Sensitivity Tests; Minocycline; Mycoplasma Infections; Oxytetracycline; Respiratory Tract Infections; Tetracyclines

Minocycline is a semi-synthetic tetracycline derivative which is well absorbed and distributed in body tissues and is suitable for twice daily administration. It appears to be as generally effective as other tetracyclines and analogues, but also to be effective in infections due to tetracycline-resistant staphylococci. Side-effects are typical of those of other tetracyclines, but minocycline has been associated with a high incidence of vertigo in some studies. On the other hand, minocycline appears to have little or no photosensitising potential. It is not yet clear whether minocycline can be safely used in patients with moderate or severe impairment of renal function, but if used in renal failure, the plasma urea concentration should be monitored.

Topics: Bacteria; Candida; Cholera; Humans; Malaria; Meningococcal Infections; Minocycline; Respiratory Tract Infections; Sexually Transmitted Diseases; Skin Diseases, Infectious; Tetracyclines; Urinary Tract Infections

Topics: Amoxicillin; Anti-Bacterial Agents; Cefazolin; Cephalosporins; Cephapirin; Cephradine; Clindamycin; Drug Combinations; Gastrointestinal Diseases; Humans; Minocycline; Penicillins; Respiratory Tract Infections; Sexually Transmitted Diseases; Sulfamethoxazole; Tobramycin; Trimethoprim; Urinary Tract Infections

Topics: Bacterial Infections; Child; Child, Preschool; Cystic Fibrosis; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Tetracyclines

Topics: Acute Disease; Aged; Bacterial Infections; Bronchitis; Bronchopneumonia; Female; Humans; Lung Diseases; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Tetracycline