minocycline and Cystic-Fibrosis

Tigecycline is a tetracycline-class antibacterial indicated for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia. It has a broad-spectrum antibacterial activity. It has identified gastrointestinal side-effects, particularly nausea and vomiting. With the increasing clinical use of tigecycline, its associated acute pancreatitis has been frequently reported in adults. However, cases of tigecycline-induced acute pancreatitis have rarely been described in children. In this study, we report a case of acute pancreatitis caused by the use of tigecycline in a child with pulmonary cystic fibrosis. In this case, abdominal pain, nausea, and vomiting occurred on the 5

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Child; Cystic Fibrosis; Humans; Minocycline; Pancreatitis; Tigecycline

Pulmonary exacerbations in cystic fibrosis (CF) are frequent events and account for a substantial proportion of the burden of morbidity and mortality in this disease. Antibacterial therapies to treat pulmonary exacerbations are instituted empirically and are individualized based on both patient factors (severity of exacerbation, frequency of exacerbation, recent courses of anti-infectives) and pathogen factors (previously isolated pathogens and in vitro predicted susceptibilities). However, the epidemiology of pathogens infecting CF airways is changing, with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Pseudomonas aeruginosa and other Gram-negative non-fermenters such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Accordingly, a great need for new and novel agents for the management of acute exacerbations in CF exists. While several antibiotics have recently been approved or are close to approval for clinical use, frequently their emphasis has been for Gram-positive, and specifically MRSA-related, disease. Despite this, these agents may have a role in CF-related exacerbations. This article reviews the spectrum of activity, pharmacokinetics and clinical and theoretical evidence for the use of newer agents including tigecycline, doripenem and ceftobiprole in the management of CF pulmonary exacerbations. Appropriate use of these agents in CF will require detailed CF-specific pharmacokinetic and pharmacodynamic data.

Topics: Achromobacter denitrificans; Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cystic Fibrosis; Doripenem; Humans; Minocycline; Pneumonia, Bacterial; Pseudomonas aeruginosa; Staphylococcus aureus; Stenotrophomonas maltophilia; 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

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

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

The purpose of this case report is to increase awareness of tigecycline-associated pancreatitis, specifically in patients who may be predisposed to develop pancreatitis.. A 22-year-old male with cystic fibrosis developed acute bronchitis, with sputum cultures significant for Mycobacterium chelonae. He was started on tigecycline on two separate occasions, in each case developing pancreatitis as evidenced by symptomatology, elevated pancreatic enzymes and, in one case, by CT imaging. On both occasions, symptomatology improved and enzymes normalized after discontinuation of tigecycline.. Current literature including two recent review pieces is discussed. The unique aspects of the case are highlighted, including the particular risk of drug-associated pancreatitis in those with cystic fibrosis.. The results of this case, in the context of current literature, suggest that clinicians should be aware of the potential for pancreatitis when using tigecycline. Clinicians should be particularly mindful of this complication in patients with comorbidities that might increase the risk of pancreatitis above that of the general population.

Topics: Anti-Bacterial Agents; Bronchitis; Cystic Fibrosis; Disease Management; Humans; Male; Minocycline; Mycobacterium chelonae; Pancreatitis; Risk Adjustment; Tigecycline; Treatment Outcome; Young Adult

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

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

We report the first case of anaphylaxis to oral vancomycin in a cystic fibrosis patient with severe and relapsing Clostridium difficile infection (CDI) refractory to metronidazole. The patient's colitis has been successfully treated with a combination of intravenous metronidazole and tigecycline.

Topics: Administration, Oral; Adult; Anaphylaxis; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cystic Fibrosis; Diarrhea; Enterocolitis, Pseudomembranous; Humans; Male; Metronidazole; Minocycline; Severity of Illness Index; Tigecycline; Vancomycin

Topics: Anti-Bacterial Agents; Bronchopneumonia; Cystic Fibrosis; Humans; Minocycline; Pneumonia, Bacterial; Tetracyclines; Tigecycline; Treatment Outcome

Susceptibility (18 antimicrobial agents including high-dose tobramycin) and checkerboard synergy (23 combinations) studies were performed for 2,621 strains of Burkholderia cepacia complex isolated from 1,257 cystic fibrosis patients. Minocycline, meropenem, and ceftazidime were the most active, inhibiting 38%, 26%, and 23% of strains, respectively. Synergy was rarely noted (range, 1% to 15% of strains per antibiotic combination).

Topics: Anti-Bacterial Agents; Burkholderia cepacia complex; Burkholderia Infections; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests

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

Minocycline hydrochloride was given to 100 patients with cystic fibrosis of the pancreas for periods of 3 months over a broad-spectrum antibiotic drug rotation which lasted 2 years. Increased weight gain and some clinical improvement was seen during treatment with minocycline. Those patients with severe disease gained more weight than those with mild or moderate disease, and males gained more than females. When minocycline hydrochloride was not the drug in use, patients lost weight and their health declined.

Topics: Adolescent; Adult; Body Weight; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Male; Minocycline; Sex Factors; Sputum; Stimulation, Chemical; Tetracyclines

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