colistin and Chronic-Disease

Historically, the polymyxin antibacterial colistin has been administered as intravenous or nebulized colistimethate sodium in patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. More recently, colistimethate sodium has been formulated as a dry powder (Colobreathe(®)) to be administered via a hand-held Turbospin(®) inhaler. Compared with nebulized colistimethate sodium, the colistimethate sodium dry powder for inhalation (DPI) formulation reduces treatment time and improves patient convenience. Colistimethate sodium DPI is approved in the EU for the treatment of chronic P. aeruginosa infections in patients with CF aged ≥6 years. In a phase III clinical trial in this patient population, it was determined that the change in percent predicted forced expiratory volume in 1 s with colistimethate sodium DPI 1.6625 MIU (125 mg) twice daily was noninferior to that with nebulized tobramycin 300 mg/5 mL twice daily. Moreover, patients found colistimethate sodium DPI easier to use than nebulized tobramycin. Colistimethate sodium DPI was generally well tolerated, with a similar adverse event profile to that of nebulized tobramycin, except for a numerically higher incidence of cough and abnormal taste. Most adverse events diminished after 28 days in patients receiving colistimethate sodium DPI, with an occurrence similar to that in nebulized tobramycin recipients. In conclusion, colistimethate sodium DPI administered via the Turbospin® inhaler is a useful option for the treatment of chronic P. aeruginosa infection in patients with CF aged ≥6 years.

Topics: Chronic Disease; Colistin; Cystic Fibrosis; Drug Resistance, Bacterial; Dry Powder Inhalers; Humans; Lung; Pseudomonas aeruginosa; Pseudomonas Infections

Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients.. To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV1 and mean sputum P. aeruginosa density were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS.. Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Aztreonam; Chronic Disease; Colistin; Cystic Fibrosis; Humans; Lung Diseases; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Tobramycin

Various inhaled antibiotics are currently used for treating chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients, however their relative efficacies are unclear. We compared the efficacy of the inhaled antibiotics tobramycin (TIP, TIS-T, TIS-B), colistimethate sodium (colistin) and aztreonam lysine for inhalation (AZLI) based on data from randomised controlled trials.. In the base case, efficacies of antibiotics were compared using a network meta-analysis of seven trials including change from baseline in forced expiratory volume in 1 second (FEV(1)) % predicted, P. aeruginosa sputum density and acute exacerbations.. The tobramycin preparations, AZLI and colistin, showed comparable improvements in efficacy in terms of FEV1% predicted at 4 weeks; the difference in % change from baseline (95%CrI) for TIP was compared to TIS-T (-0.55, -3.5;2.4), TIS-B (-0.64, -7.1;5.7), AZLI (3.64, -1.0;8.3) and colistin (5.77, -1.2;12.8).. We conclude that all studied antibiotics have comparable efficacies for the treatment of chronic P. aeruginosa lung infection in CF.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Aztreonam; Bacterial Load; Bayes Theorem; Biological Availability; Chronic Disease; Colistin; Cystic Fibrosis; Disease Progression; Female; Forced Expiratory Volume; Humans; Information Services; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Tobramycin; Treatment Outcome

Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Denmark; Humans; Incidence; Pseudomonas Infections

In chronic otitis, the use of ear drops has certain advantages over the use of systemic antibiotics. The choice of ear drop depends on the condition of the eardrum, microbial pathogens present and the efficacy of the components of the ear drop. Ototoxicity, contact allergy and the development of bacterial resistance have to be taken into account. Ototoxicity is a rare complication of the application of ear drops, most often described when aminoglycosides were applied. Contact allergy is also most often seen in aminoglycoside-containing eardrops. Evaluation of ear swabs demonstrated a 5% resistance of Pseudomonas aeruginosa to ciprofloxacin. The appearance of resistant strains may impede systemic use of fluoroquinolones. Therefore, this class of antibiotics should be considered as reserve medication only. The first choice in local application of antiseptics in case of an open eardrum is aluminium acetotartrate 1.2% and, of a combination preparation, bacitracin-colistin-hydrocortisone. In case of a closed eardrum (external otitis) aluminium acetotartrate 12%--combination preparations with corticosteroids are advised against in these cases.

Topics: Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents, Local; Anti-Inflammatory Agents; Bacitracin; Chronic Disease; Colistin; Drug Therapy, Combination; Ear, External; Humans; Hydrocortisone; Netherlands; Otitis Media, Suppurative; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Tartrates

Topics: Administration, Inhalation; Anti-Bacterial Agents; Chronic Disease; Colistin; Community Health Centers; Cystic Fibrosis; Drug Resistance, Microbial; Humans; Injections, Intravenous; Prognosis; Pseudomonas aeruginosa; Pseudomonas Infections

Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis.. To perform a randomized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection.. Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation. Participants were randomized to receive colistin (1 million IU; n = 73) or placebo (0.45% saline; n = 71) via the I-neb twice a day, for up to 6 months.. The primary endpoint was time to exacerbation. Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb, P. aeruginosa bacterial density, quality of life, and safety parameters. All analyses were on the intention-to-treat population. Median time (25% quartile) to exacerbation was 165 (42) versus 111 (52) days in the colistin and placebo groups, respectively (P = 0.11). In adherent patients (adherence quartiles 2-4), the median time to exacerbation was 168 (65) versus 103 (37) days in the colistin and placebo groups, respectively (P = 0.038). P. aeruginosa density was reduced after 4 (P = 0.001) and 12 weeks (P = 0.008) and the St. George's Respiratory Questionnaire total score was improved after 26 weeks (P = 0.006) in the colistin versus placebo patients, respectively. There were no safety concerns.. Although the primary endpoint was not reached, this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection. Clinical trial registered with http://www.isrctn.org/ (ISRCTN49790596).

Topics: Administration, Inhalation; Adult; Aged; Anti-Bacterial Agents; Bronchiectasis; Chronic Disease; Colistin; Double-Blind Method; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Quality of Life; Russia; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ukraine; United Kingdom

Despite optimal medical therapy and endoscopic sinus surgery there still remains a group of unfortunate patients suffering from exacerbations of recalcitrant chronic sinusitis. We have performed a pilot study in order to determine whether nebulized topical antibiotic therapy improves sinusitis symptoms more than saline-based placebo in patients with recalcitrant chronic rhinosinusitis.. A randomized, placebo-controlled, double-blind, cross-over pilot study was conducted in 14 patients with recalcitrant CRS. Nasal irrigation with bacitracin/colimycin or placebo using the RhinoFlow nebulizer twice daily was administered in combination with oral levofloxacin. Severity of a diversity of symptoms was measured using the VAS score, a Disease-Specific Symptom Score and the SF-36 questionnaire. Nasal endoscopic findings were also assessed.. For most VAS items and Disease-Specific Symptom Scores, a reduction in severity of symptoms was noted in both the bacitracin/colimycin and the placebo group. No significant difference was found between the 2 arms (bacitracin/colimycin vs. placebo). Most SF-36 items improved, compared with the situation before treatment in both groups. However no significant difference was found between the verum and placebo arm. Endoscopic findings did not reveal significant differences when comparing the 2 treatments.. The outcome of this study suggests a beneficial effect of nebulizing the nose with saline. This study again shows that adding antibiotics to local saline is not effective. Although the placebo-controlled studies looking at the effect of local antibiotics are all small they all point to the same direction: no effect. Definite conclusions however need a large randomized, multicenter study.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacitracin; Chronic Disease; Colistin; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levofloxacin; Male; Middle Aged; Nebulizers and Vaporizers; Ofloxacin; Pilot Projects; Rhinitis; Sinusitis; Staphylococcal Infections; Staphylococcus aureus

Recurrent Gram-negative bacterial infection is a significant cause of death in patients with bronchiectasis and severe chronic obstructive pulmonary disease (COPD). Nebulized colistin in cystic fibrosis has shown maintenance of pulmonary function and improved symptom scores. We prospectively followed 18 patients with chronic bronchial sepsis treated with nebulized colistin 30 mg daily. Mean decline in forced expiratory volume in 1 s was significantly slower following commencement of inhaled colistin (44 mL/year vs 104 mL/year, P = 0.035). Mean decline in forced vital capacity was also significantly slower following commencement of colistin (48 mL/year vs 110 mL/year, P = 0.033). Patient-reported quality of life improved following commencement of colistin (3.6 vs 6.2, P = 0.001). No patient had isolates resistant to colistin. No side-effects were reported by patients in the cohort. Use of inhaled colistin in the treatment of bronchiectasis and severe (COPD) in patients with recurrent Gram-negative infections is safe. Inhaled colistin may improve quality of life and slow decline in forced expiratory volume in 1 s and forced vital capacity.

Topics: Administration, Inhalation; Aged; Anti-Bacterial Agents; Bronchiectasis; Chronic Disease; Colistin; Female; Humans; Male; Nebulizers and Vaporizers; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Time Factors; Treatment Outcome

A previous study of tobramycin nebuliser solution (TNS) compared with colistin [C] in cystic fibrosis (CF) patients, chronically infected with pseudomonas, showed benefit for the TNS treated patients over one treatment cycle only. The current report is of an extension of that study. An open randomised cross-over study of TNS compared with C was conducted on 21 patients who had previously been on the 1 cycle study. They continued for a further 5 months and then crossed over to the alternate treatment. There was an advantage for TNS over C in FEV(1) % predicted change over time. The C slope was -0.88% per month and the TNS slope 0.35% per month (p=0.0002). This suggests advantages of TNS over C in a study with a small number of patients. Larger studies are required.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Chronic Disease; Colistin; Cross-Over Studies; Cystic Fibrosis; Female; Follow-Up Studies; Humans; Male; Pseudomonas Infections; Tobramycin

Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis (CF) patients. The purpose of this trial was to assess the efficacy and safety of tobramycin nebuliser solution (TNS) and nebulised colistin in CF patients chronically infected with P. aeruginosa. One-hundred and fifteen patients, aged > or = 6 yrs, were randomised to receive either TNS or colistin, twice daily for 4 weeks. The primary end point was an evaluation of the relative change in lung function from baseline, as measured by forced expiratory volume in one second % predicted. Secondary end points included changes in sputum P. aeruginosa density, tobramycin/colistin minimum inhibitory concentrations and safety assessments. TNS produced a mean 6.7% improvement in lung function (p=0.006), whilst there was no significant improvement in the colistin-treated patients (mean change 0.37%). Both nebulised antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density, and there was no development of highly resistant strains over the course of the study. The safety profile for both nebulised antibiotics was good. Tobramycin nebuliser solution significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa, but colistin did not, in this study of 1-month's duration. Both treatments reduced the bacterial load.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Anti-Bacterial Agents; Child; Chronic Disease; Colistin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Chronic pulmonary infection with Pseudomonas aeruginosa (PA) develops in most patients with cystic fibrosis (CF) and is associated with a poor prognosis. Much effort has been directed toward treating the chronic infection, but it is almost impossible to eradicate it once established; therefore, prevention is preferable. Since 1989 CF patients at the Danish CF Center in Copenhagen have been treated with an intensive three-step-protocol consisting of colistin inhalations and oral ciprofloxacin at the time of initial PA colonization. This study compares 48 patients treated according to this intensive protocol with 43 historic controls. The study was carried out over 44 months and included 218 patient-years. Only 16% of the treated patients developed chronic PA infection after 3 1/2 years compared with 72% of the control patients (Kaplan Meier estimate, P < 0.005, log rank test). This indicates that aggressive treatment prevented or delayed chronic PA infection in 78% of the patients for 3 1/2 years. Furthermore, aggressive treatment maintained or increased pulmonary function (forced vital capacity and forced expiratory volume in 1 second in percent of predicted values) during the year after inclusion compared with the control group, in which pulmonary function declined (P < 0.01, Mann-Whitney test). Although some of the treated patients eventually developed chronic PA infection, these patients had significantly better pulmonary function at the onset of chronic PA infection compared with control patients (P < 0.001, Mann-Whitney test). When the different steps in the intensive three-step-protocol were analyzed, there was a trend suggesting that 3 months of high-dose treatment with colistin inhalation and oral ciprofloxacin produced the best results in terms of postponement or prevention of chronic PA infection (P < 0.05).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Carrier State; Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Infant; Lung Diseases; Male; Proportional Hazards Models; Pseudomonas aeruginosa; Pseudomonas Infections; Statistics, Nonparametric; Vital Capacity

Topics: Adolescent; Aerosols; Bronchial Diseases; Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Time Factors

To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy.

Topics: Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospective double-blind placebo-controlled study of colistin inhalation. Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline. Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group (18 versus 11). Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score, maintenance of pulmonary function and inflammatory parameters. We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy.

Topics: Administration, Inhalation; Adolescent; Adult; Child; Chronic Disease; Clinical Trials as Topic; Colistin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Pseudomonas Infections; Vital Capacity

This study was designed to compare the efficacy and safety of gentamicin otic solution versus colistin-neomycin-hydrocortisone otic suspension in the treatment of otorrhoea due to infection. Fifty-five patients (mean age 36.6 +/- 22.1 years) with sixty infected ears with otorrhoea complicating otitis externa, recurrent otitis media with tympanic membrane perforation, or infected mastoid cavities and post-operative tympanoplasties, were treated for 14 days with either an aqueous solution of gentamicin 0.3% or an aqueous suspension of colistin 0.3%, neomycin 0.33% and hydrocortisone 1.0%. The two possible treatments were assigned randomly and the results were assessed double-blind using usual ordinal scales for monitoring the severity of symptoms. Both otic preparations were found to be equally safe in the treatment of otorrhoea due to infection. No side-effects were observed and hearing status was either unchanged or improved. The antibiotic-steroid combination appeared to be more effective in relieving inflammation in a shorter period of time while gentamicin was observed to be more effective in eradicating the infecting organisms.

Topics: Adult; Bacterial Infections; Chronic Disease; Clinical Trials as Topic; Colistin; Double-Blind Method; Gentamicins; Hearing; Humans; Hydrocortisone; Neomycin; Otitis; Otitis Externa; Otitis Media; Tympanoplasty

Topics: Adult; Aerosols; Aged; Bronchitis; Chronic Disease; Colistin; Dyspnea; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Histamine H1 Antagonists; Humans; Kanamycin; Male; Middle Aged; Pseudomonas; Pseudomonas Infections; Respiratory Therapy; Sputum; Ventilators, Mechanical; Virulence

The presented study was to compare in vitro biofilm production by bacterial strains from chronic/recurrent and from acute non-complicated UTIs. The activity of gentamicin and colistin on biofilm form of these strains has also been detected, with goal to predict the gentamicin and colistin therapeutic efficacy in the antimicrobial treatment of patients with a suspected presence of biofilm in urinary tract.. The group of 40 bacterial strains repeatedly isolated from patients with chronic or recurrent UTIs was compared with the group of 40 strains from acute UTIs. Both groups contained comparable number of strains of Escherichia coli, Klebsiella spp., Proteus mirabilis and Pseudomonas aeruginosa. Biofilm production was assessed by method in polystyrene microtiter plate. The MIC and MBC values of gentamicin and colistin were detected by broth microdilution assay. The minimal biofilm inhibitory (MBIC) and biofilm eradication concentrations (MBEC) were tested by microdilution method. Non-inactivated biofilm-associated bacteria were detected after overnight incubation in broth medium free of antimicrobials. The statistical analysis of results was performed by Fisher's exact test and by Student's t-test.. Biofilm was produced by 90% strains from chronic UTIs, but only by 52% of strains from acute UTIs (p = 0.0004). In the biofilm producing strains, the MBIC values of gentamicin reached from four to 256 mg/L, the MBIC levels of colistin from two to 64 mg/L. The minimal biofilm eradicating concentrations were even higher: for gentamicin from eight to > 512 mg/L, and for colistin from 32 to > 512 mg/L. The differences between MIC and MBIC/MBEC levels were statistically highly significant (p < 0.0001). Presumably, the therapeutic success of parenterally applied gentamicin or colistin on biofilm-related urinary tract infections would be, without respect to the high concentration of gentamicin or colistin achievable in urine during parenteral application, rather unpredictable. Local intravesical instillation would allow for achieving higher gentamicin and colistin concentrations; however, there is need for interpretation criteria for MBEC values concerning therapy, as well as for clinical studies allowing for application of those values to predict clinical success of therapy.. Laboratory detection of biofilm production and evaluation of the MBIC/MBEC values of antimicrobials for strains producing biofilm might be a valuable complement to the microbiologic diagnostics of chronic and recurrent UTIs. It might provide valuable information for more reliable individualised therapy and so decrease the risk of emergence and selection of multiresistant strains during repeated and non-eradicating therapy of chronic and recurrent UTIs.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Physiological Phenomena; Biofilms; Chronic Disease; Colistin; Gentamicins; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Urinary Tract Infections

Topics: Achromobacter; Anti-Bacterial Agents; Chronic Disease; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Middle Aged; Otitis Media, Suppurative

In cystic fibrosis (CF), chronic microbial lung infections are difficult to treat and cause morbidity and increased mortality.. In a multicentre, open-label, exploratory, non-interventional study, inhaled tobramycin (300 mg twice daily) and colistin (1 million I.U. twice daily) were sequentially combined with the aim to investigate the effect on 41 CF patients with chronic P. aeruginosa infections for six months (mean age 24 ± 10.8y).. Six patients had adverse events that were assessed as being related to treatment. Mucus production and coughing both decreased in 39%, whereas FEV1 absolute and relative to baseline increased by 4.9% and 9.1%, respectively (p = 0.004) in 29 patients, who were definitely treated sequentially. Efficacy of the therapy was rated 'excellent' or 'good' by the physicians in 80.5% of the patients.. The results indicate that treatment with inhaled antibiotics, sequentially combined, was very well tolerated by most patients and may have a beneficial effect, even if transitory on lung function and respiratory symptoms.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Chronic Disease; Colistin; Cystic Fibrosis; Drug Administration Schedule; Drug Combinations; Female; Forced Expiratory Volume; Humans; Male; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

The spread of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae continues to increase, and the possible development of KPC-producing K. pneumoniae infections in cystic fibrosis (CF) patients is a matter of concern. Here, we describe the establishment of a chronic lung infection due to a colistin-resistant KPC-producing K. pneumoniae isolate in an Italian CF patient.

Topics: Anti-Bacterial Agents; Chronic Disease; Colistin; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Underage Drinking

Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS).. We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota communities after infection. Whilst treatment with CMS appeared to have little impact on microbial community composition after infection, or the change undergone by communities in reaching that state, when Gram negative organisms (excluding Pseudomonadales) were considered together as a group there was a significant decrease in their relative proportion that was only observed in the sheep treated with CMS. With only one exception the reduction was seen in both direct and remote lung segments. This reduction, coupled with generally increasing or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment.. The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bronchoalveolar Lavage Fluid; Chronic Disease; Colistin; Disease Models, Animal; Female; Injections, Intravenous; Lung; Male; Microbiota; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sheep, Domestic

Most patients with cystic fibrosis (CF) have chronic rhinosinusitis; their sinuses are often colonized with bacteria that can initiate and maintain deleterious pulmonary infections. Theoretically, eradication of the sinus bacteria should reduce the frequency of lung infections and thereby reduce pulmonary morbidity. This article addressed whether bacteria in CF sinuses are eligible for eradication by sinus surgery and postoperative treatment.. A prospective study including 58 CF patients, who had extensive sinus surgery and growth of Pseudomonas aeruginosa, Achromobacter xylosoxidans, and/or Burkholderia multivorans in their sinuses, was initiated. All patients followed a systematic postoperative treatment program of nasal irrigations with saline and colistimethate sodium and systematic endoscopic cleansing. All patients had follow-up examinations including sinus cultures; each side of the nose was cultured separately.. At the 6-month follow-up visit, 49 patients were cultured; 66 of 98 maxillary-ethmoidal complexes (67%) showed no growth of pathogenic bacteria. Some patients were not free from CF pathogenic bacteria at all cultures; however, 20 (41%) patients had no bilateral regrowth (p < 0.01) and 4 patients had no unilateral regrowth at any time during 6 months of follow-up. The eradication of CF pathogens was accomplished in patients from all three lung infection groups: intermittently colonized, chronically infected, and lung transplanted. The patient with the longest follow-up had no bacterial growth for 3 years.. Extensive sinus surgery combined with intensive follow-up can eradicate pathogenic bacteria from CF sinuses.

Topics: Achromobacter denitrificans; Adolescent; Adult; Burkholderia; Burkholderia Infections; Child; Chronic Disease; Colistin; Cystic Fibrosis; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Nasal Lavage; Paranasal Sinuses; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Rhinitis; Sinusitis; Treatment Outcome; Young Adult

Squalamine is a steroid extracted from sharks with proven in vitro antibacterial activity. We assessed its efficacy in reducing the lung bacterial load and histological lesions when given via inhalation in a rat model of chronic Pseudomonas aeruginosa pneumonia.. Sprague-Dawley rats were inoculated by tracheal intubation with 150 μL of a solution containing 10(8) cfu/mL of agar bead-embedded P. aeruginosa strain PAO1. MICs of squalamine and colistin for this strain were 2-8 and 0.5-1 mg/L, respectively. Starting the day after infection, the animals were treated twice daily with aerosolized squalamine (3 mg), colistin (160 mg) or 0.9% saline for 6 days. The bacterial load and lung histological lesions were evaluated on the seventh day.. Aerosols of squalamine and colistin resulted in a significant reduction in median (IQR) pulmonary bacterial count compared with saline [10(3) (6 × 10(2)-2 × 10(3)), 10(3) (9 × 10(2)-6 × 10(3)) and 10(5) (9 × 10(4)-2 × 10(5)) cfu/lung, respectively; P < 0.001 for both treated groups versus saline]. The lung weight and the lung histological severity score were significantly lower in both treated groups.. In a model of chronic P. aeruginosa pneumonia, treatment twice daily with a squalamine aerosol for 6 days leads to a significant reduction in the pulmonary bacterial count and pneumonia lesions with an efficacy comparable to that of colistin.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Bacterial Load; Cholestanols; Chronic Disease; Colistin; Disease Models, Animal; Lung; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Treatment Outcome

Tobramycin and colistin represent 2 standard antimicrobial agents in the treatment of cystic fibrosis (CF) patients who are chronically colonized with Pseudomonas aeruginosa. In this study, we determined the rate of resistance to tobramycin and colistin in 1844 isolates of P. aeruginosa obtained from 22 CF patients under alternate therapy with inhaled tobramycin and colistin. Resistance to tobramycin was observed in 27.5% of isolates. In contrast, all isolates were susceptible to colistin. Molecular typing of selected isolates suggested that only 1 clone occurred over time in each patient. To conclude, resistance to tobramycin in P. aeruginosa isolates from CF patients under antimicrobial therapy may occur while colistin resistance remains uncommon.

Topics: Adult; Anti-Bacterial Agents; Bacterial Typing Techniques; Chronic Disease; Cluster Analysis; Colistin; Cystic Fibrosis; DNA Fingerprinting; Drug Resistance, Bacterial; Female; Genotype; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Topics: Adult; Anti-Bacterial Agents; Ceftazidime; Child, Preschool; Chronic Disease; Ciprofloxacin; Clavulanic Acids; Colistin; Cost of Illness; Cystic Fibrosis; Humans; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins; Ticarcillin; Tobramycin

Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment.. All isolates of P. aeruginosa from CF-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non-mucoid or mucoid phenotype.. 146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. 613 colistin/ciprofloxacin treatments were given. There was no difference in pseudomonas-free interval comparing 3 weeks (5 months) and 3 months (10.4 months) of colistin and ciprofloxacin, but a significant difference compared to no treatment (1.9 months). Patients developing chronic infection had significantly shorter pseudomonas-free interval after treatment of first ever isolate compared to patients remaining intermittently colonized (p<0.003). Treatment failure (P. aeruginosa-positive culture immediately after ended treatment of first ever isolate) was a strong risk factor for development of chronic infection after 3-4 years, OR 5.8. 1093 pseudomonas-isolates were evaluated (86.6% non-mucoid). No colistin-resistance was found. Ciprofloxacin-resistance was found in 4% of isolates.. Treatment of intermittent P. aeruginosa colonization in CF-patients using colistin and ciprofloxacin can protect up to 80% of patients from development of chronic infection for up to 15 years. A positive culture immediately after treatment of first ever isolate is a strong risk factor for development of chronic infection. We found no colistin-resistance and minimal ciprofloxacin-resistance.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Cohort Studies; Colistin; Cystic Fibrosis; Disease-Free Survival; Female; Humans; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Anti-Bacterial Agents; Chronic Disease; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections

Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV beta-lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain. Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination.

Topics: Administration, Inhalation; Administration, Oral; Ceftazidime; Child; Child, Preschool; Chronic Disease; Colistin; Colony Count, Microbial; Cystic Fibrosis; DNA, Bacterial; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Imipenem; Infant; Male; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Assessment; Tobramycin

Antibiotic therapy with colbiocin of chronic purulent mesotympanitis achieved a response rate of 92%, recurrence-free interval reached 6 months in 84% of the treated patients. This allows to recommend colbiocin as a drug of choice in hospital and outpatient treatment of chronic purulent mesotympanitis.

Topics: Chloramphenicol; Chronic Disease; Colistin; Drug Therapy, Combination; Humans; Otitis Media, Suppurative; Tetracycline

The bacteriological effect of chemotherapy against Pseudomonas aeruginosa (Ps.ae.) in lungs of patients with cystic fibrosis is reviewed. During a 5-year period 49 children and adults were treated with 190 courses of different antibiotics. The mucoid strains of Ps.ae. disappeared in 72.0% of the courses in which a combination of tobramycin and carbenicillin was employed. Tobramycin given alone had only bacteriological effect in 26.6% of the courses. Colimycin alone or in combination with carbenicillin had no effect. In 18 patients who received subsequent courses of tobramycin and combination of tobramycin and carbenicillin a significant difference in favour of the combination therapy was found, also in cases with many precipitins against Ps.ae. in serum. In 74.5% of the initially successful courses the patients were recolonized with Ps.ae. within 1 month. No nephrotoxic or ototoxic side effects were demonstrated in spite of the high doses of tobramycin (10 mg/kg/24 h) emmployed and the repeated courses.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbenicillin; Child; Child, Preschool; Chronic Disease; Colistin; Cystic Fibrosis; Drug Evaluation; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Male; Pneumonia; Precipitins; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no antimicrobial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.

Topics: Anti-Bacterial Agents; Carbenicillin; Chronic Disease; Colistin; Cross Infection; Gentamicins; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Neoplasms; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Acute Disease; Anti-Bacterial Agents; Chloramphenicol; Cholecystitis; Chronic Disease; Colistin; Escherichia coli Infections; Penicillins; Staphylococcal Infections; Streptococcal Infections; Streptomycin

Topics: Adult; Aged; Ampicillin; Anti-Bacterial Agents; Chloramphenicol; Chronic Disease; Colistin; Depression, Chemical; Drug Synergism; Erythromycin; Escherichia coli Infections; Female; Follow-Up Studies; Humans; Kanamycin; Klebsiella Infections; Male; Middle Aged; Nitrofurantoin; Oleandomycin; Oxacillin; Penicillins; Polymyxins; Proteus Infections; Pyelonephritis; Staphylococcal Infections; Stimulation, Chemical; Streptococcal Infections; Streptomycin; Sulfonamides; Tetracycline

Topics: Adolescent; Adult; Aged; Bacteriuria; Cephalothin; Chloramphenicol; Chronic Disease; Colistin; Drug Resistance, Microbial; Escherichia coli Infections; Female; Gentamicins; Humans; Kanamycin; Male; Methacycline; Middle Aged; Oxytetracycline; Proteus Infections; Rifampin; Sulfamethoxypyridazine; Urinary Tract Infections

Topics: Acrylates; Anti-Bacterial Agents; Bacitracin; Chloramphenicol; Chronic Disease; Colistin; Gels; Gentamicins; Humans; Methods; Otitis Media; Postoperative Complications; Tympanoplasty

Topics: Albuminuria; Cholangitis; Chronic Disease; Colistin; Hematuria; Humans; Pyelonephritis; Urinary Tract Infections

Topics: Bacteria; Chloramphenicol; Chronic Disease; Colistin; Escherichia coli; Humans; Iodine; Kanamycin; Klebsiella; Proteus; Pseudomonas aeruginosa; Urinary Bladder Calculi; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Bacillus; Bacteria; Chloramphenicol; Chlortetracycline; Chronic Disease; Colistin; Corynebacterium; Depression, Chemical; Erythromycin; Erythromycin Ethylsuccinate; Escherichia coli; Humans; Microbial Sensitivity Tests; Nasal Mucosa; Otitis Media; Oxytetracycline; Penicillin Resistance; Penicillins; Proteus; Pseudomonas aeruginosa; Staphylococcus; Streptomycin; Suppuration; Tetracycline

Topics: Administration, Oral; Adolescent; Adult; Aged; Blood Sedimentation; C-Reactive Protein; Child; Chloramphenicol; Chronic Disease; Cloxacillin; Colistin; Female; Fistula; Humans; Injections; Male; Middle Aged; Osteomyelitis; Probenecid; Prognosis; Recurrence; Staphylococcal Infections; Staphylococcus

Topics: Acute Kidney Injury; Adult; Ampicillin; Cephalothin; Chloramphenicol; Chronic Disease; Colistin; Humans; Male; Pyelonephritis; Urinary Tract Infections

Gentamicin was of value in the treatment of chronic urinary tract infections caused by multiresistant bacterial strains for which no atoxic antibiotic was available. The treatment was carried out after alkalinization of the patient's urine. With the dosage given, gentamicin gave a low serum and a relatively high urine concentration. Excretion of active gentamicin in the urine was high even in patients with impaired renal function. The results of treatment of complicated chronic urinary tract infections with initial gentamicin and following long-term therapy showed negative urinary cultures in 12 out of 24 patients within one to 14 months of follow-up time. To reduce the risk of toxic side effects the dosage was adjusted according to the patient's kidney function. No development of resistance was demonstrated in the bacteria.

Topics: Adult; Aged; Chronic Disease; Colistin; Drug Resistance, Microbial; Escherichia coli Infections; Female; Gentamicins; Humans; Kanamycin; Klebsiella Infections; Male; Middle Aged; Proteus Infections; Urinary Tract Infections

Topics: Adult; Anti-Bacterial Agents; Blood Transfusion; Chronic Disease; Colistin; Dysentery, Amebic; Dysentery, Bacillary; Humans; Male

Topics: Ampicillin; Anti-Infective Agents, Urinary; Chloramphenicol; Chronic Disease; Colistin; Humans; Nalidixic Acid; Nitrofurantoin; Pyelonephritis; Sulfonamides; Tetracycline

Topics: Chronic Disease; Colistin; Humans; Pyelonephritis