trimethoprim--sulfamethoxazole-drug-combination and Cystic-Fibrosis

Cepacia syndrome (CS) is an acute, necrotizing pneumonia with a high mortality rate, occurring in patients with cystic fibrosis (CF) infected with Burkholderia cepacia complex (BCC). Due to its low incidence, data on this condition are limited.. We conducted a systematic review of the reported cases of CS by searching MEDLINE, Embase and the Cochrane Library to improve knowledge of this rare but potentially lethal condition.. We included 15 eligible articles, describing 18 cases (9 females) of CS. Median age at onset was 22 years (range: 10-60 years); median time to CS after first infection by BCC was 5 years (range: 1-26 years). Burkholderia cenocepacia was the most frequently reported causative agent. All patients received intravenous antibiotic treatment (most frequently including cotrimoxazole), while inhaled antibiotics were used in five patients (27.8%). Immunosuppressant agents were the most commonly prescribed supportive treatment (n = 7, 38.9%). Half of the patients died (9/18, 50%).. This study describes epidemiological, clinical characteristics, and prognosis of CS cases reported over the last 24 years. CS is a rare yet severe complication of BCC infection in patients with CF, which occurs several years after BCC colonization and has a negative outcome in 50% of the patients. Data are too scanty to identify the most effective therapeutic approach.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Burkholderia cepacia complex; Burkholderia Infections; Child; Cystic Fibrosis; Female; Humans; Middle Aged; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pandoraea spp. are gram-negative, nonfermenting rods mainly known to infect patients with cystic fibrosis (CF). Outbreaks have been reported from several CF centers. We report a Pandoraea spp. outbreak comprising 24 non-CF patients at a large university hospital and a neighboring heart center in Germany during July 2019-December 2021. Common features in the patients were critical illness, invasive ventilation, antimicrobial pretreatment, and preceding surgery. Complicated and relapsing clinical courses were observed in cases with intraabdominal infections but not those with lower respiratory tract infections. Genomic analysis of 15 isolates identified Pandoraea commovens as the genetically most similar species and confirmed the clonality of the outbreak strain, designated P. commovens strain LB-19-202-79. The strain exhibited resistance to most antimicrobial drugs except ampicillin/sulbactam, imipenem, and trimethoprim/sulfamethoxazole. Our findings suggest Pandoraea spp. can spread among non-CF patients and underscore that clinicians and microbiologists should be vigilant in detecting and assessing unusual pathogens.

Topics: Anti-Infective Agents; Burkholderiaceae; Cystic Fibrosis; Germany; Gram-Negative Bacteria; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Topics: Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Ciprofloxacin; Clindamycin; Cystic Fibrosis; Humans; Linezolid; Lipoglycopeptides; Methicillin; Methicillin-Resistant Staphylococcus aureus; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as, not only an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer people with cystic fibrosis with a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.. To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including P aeruginosa) or increased adverse effects from drugs, or both.. Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE, clinical trial registries (Clinicaltrials.gov, WHO ICTRP, ISRCTN Registry), handsearching article reference lists and through contact with experts in the field.Date of the last search of the Group's Cystic Fibrosis Trials Register: 27 July 2017.Ongoing trials registries were last searched: 07 August 2017.. Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment.. The authors independently assessed all search results for eligibility. They used the GRADE methodology to assess the quality of the evidence.. The review includes two trials with a total of 106 participants with MRSA infection. In both trials the active treatment was oral trimethoprim and sulfamethoxazole combined with rifampicin; however, one trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. In both trials the control arm was observation only.Both trials reported successful eradication of MRSA in people with CF as an outcome; however, the definition used for MRSA eradication differed. The first trial (n = 45) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that, when compared to control, oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures, odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence); however, by day 168 of follow-up there was no difference in the proportion of participants who remained MRSA-negative in either treatment arm, OR 1.17 (95% CI 0.31 to 4.42) (low-quality evidence). In the second trial, successful eradication was defined as the absence of MRSA following treatment (oral co-trimoxazole and rifampicin with intranasal mupirocin or observation) in at least three cultures over a period of six months. At the time of reporting, 40 out of 61 participants had completed follow-up, but results showed no difference between groups. Eradication was achieved in 12 out 29 participants (41%) receiving active treatment, and in 9 out of 32 participants (28%) on the observation arm, OR 1.80 (95% CI 0.62 to 5.25) (very low-quality evidence).With regards to this review's secondary outcomes, these were reported in the first trial only. The trial reports that no differences were observed between the two arms in terms of pulmonary exacerbations (from screening to day 28), nasal colonisation, lung function, weight or participant-reported outcomes. While not a specific outcome of this review, investigators reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control, rate ratio 0.22 (95% CI 0.05 to 0.72) (P = 0.0102).. Early eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, by six months, the proportion of participants who remained MRSA-negative did not differ between treatment arms in either trial. Moreover, the longer-term clinical consequences in terms of lung function, mortality and cost of care, remain unclear.Using GRADE methodology, we judged the quality of the evidence provided by this review to be very low to low, due to potential biases from the open-label design and unclear detail reported in one trial. Based on the available evidence, it is the opinion of the authors that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.

Topics: Anti-Bacterial Agents; Cystic Fibrosis; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Cystic Fibrosis; Drug Monitoring; Fluoroquinolones; Humans; Lactams; Trimethoprim, Sulfamethoxazole Drug Combination

This article provides the pulmonary specialist with a summary description of these commonly used antimicrobial agents, including mode of action, antimicrobial spectrum, pharmacology, toxicity, indications for use, and recommended dosages.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cystic Fibrosis; Drug Combinations; Drug Resistance, Microbial; Humans; Pentamidine; Pneumonia; Polymyxins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Few studies, based on a limited number of patients using non-uniform therapeutic protocols, have analyzed Methicillin-resistant Staphylococcus aureus (MRSA) eradication.. In a randomized multicenter trial conducted on patients with new-onset MRSA infection we evaluated the efficacy of an early eradication treatment (arm A) compared with an observational group (B). Arm A received oral rifampicin and trimethoprim/sulfamethoxazole (21 days). Patients' microbiological status, FEV1, BMI, pulmonary exacerbations and use of antibiotics were assessed.. Sixty-one patients were randomized. Twenty-nine (47.5%) patients were assigned to active arm A and 32 (52.5%) patients to observational arm B. Twenty-nine (47.5%) patients, 10 patients in arm A and 19 in arm B, dropped out of the study. At 6 months MRSA was eradicated in 12 (63.2%) out of 19 patients in arm A while spontaneous clearance was observed in 5 (38.5%) out of 13 patients in arm B. A per-protocol analysis showed a 24.7% difference in the proportion of MRSA clearance between the two groups (z = 1.37, P(Z>z) = 0.08). Twenty-seven patients, 15 (78.9%) out of 19 in arm A and 12 (92.3%) out of 13 in arm B, were able to perform spirometry. The mean (±SD) FEV1 change from baseline was 7.13% (±14.92) in arm A and -1.16% (±5.25) in arm B (p = 0.08). In the same period the BMI change (mean ±SD) from baseline was 0.54 (±1.33) kg/m2 in arm A and -0.38 (±1.56) kg/m2 in arm B (p = 0.08). At 6 months no statistically significant differences regarding the number of pulmonary exacerbations, days spent in hospital and use of antibiotics were observed between the two arms.. Although the statistical power of the study is limited, we found a 24.7% higher clearance of MRSA in the active arm than in the observational arm at 6 months. Patients in the active arm A also had favorable FEV1 and BMI tendencies.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Rifampin; Staphylococcal Infections; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (SXT) is the preferable treatment option of the infections caused by Achromobacter spp. Our study aimed to analyze the SXT resistance of 98 Achromobacter spp. isolates from pediatric patients, among which 33 isolates were SXT-resistant. The presence of intI1 was screened by PCR and genome sequence analyses. The intI1 gene was detected in 10 of SXT-resistant isolates that had shorter intI1 PCR fragments named intI1S. Structural changes in intI1S were confirmed by genome sequencing and analyses which revealed 86 amino acids deletion in IntI1S protein compared to canonical IntI1 protein. All IntI1S isolates were of non-CF origin. Pan-genome analysis of intI1S bearing A. xylosoxidans isolates comprised 9052 genes, with the core genome consisting of 5455 protein-coding genes. Results in this study indicate that IntI1S isolates were derived from clinical settings and that cystic fibrosis (CF) patients were potential reservoirs for healthcare-associated infections that occurred in non-CF patients.

Topics: Achromobacter; Achromobacter denitrificans; Anti-Bacterial Agents; Child; Cystic Fibrosis; Genomics; Gram-Negative Bacterial Infections; Humans; Integrases; Integrons; Microbial Sensitivity Tests; Serbia; Trimethoprim, Sulfamethoxazole Drug Combination

Antibiotic allergy is a big problem that may affect the treatment and life quality of patients with cystic fibrosis (CF).. To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF.. In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression.. β-lactam allergy was confirmed in eight patients (ceftazidime n = 5, piperacillin-tazobactam n = 3) and non-β-lactam allergy was confirmed in two patients (ciprofloxacin n = 1, azithromycin n = 1). Additionally, multiple drug hypersensitivity in five patients (distant n = 4, sequential n = 1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n = 2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n = 13) with confirmed β-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, p < 0.001) and allergic evaluation in the first six months after the reaction (p = 0.036) were significant risk factors for the prediction of antibiotic hypersensitivity.. Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority.

Topics: Amikacin; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Ceftazidime; Child; Ciprofloxacin; Cystic Fibrosis; Drug Hypersensitivity; Humans; Levofloxacin; Meropenem; Piperacillin; Retrospective Studies; Tazobactam; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a retrospective study of patients yielding ⩾1 respiratory. Seven hundred and forty isolates were identified from 238 patients (median 1.0 isolate/patient). Predisposing conditions included invasive ventilation (29.8%), CF (25.6%) and non-CF bronchiectasis (24.4%). The rates of

Topics: Anti-Bacterial Agents; Cohort Studies; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Lung; Retrospective Studies; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

In the management of cystic fibrosis, treatments against Staphylococcus aureus and Haemophilus influenzae such as amoxicillin or cotrimoxazole have to be prescribed and the antibiotherapy's efficacy may be linked to the concentration that reaches the infected site. As cystic fibrosis patients present disturbed pharmacokinetics parameters, drug monitoring would be relevant to assess the lung distribution of antibiotics and to optimize dosing regimens. In this context, the aim of the study was to develop and validate HPLC-based methods for the determination of both antibiotics in bronchial sputum from cystic fibrosis patients, in order to assess the distribution of the drugs into the lungs. Plasma proteins were precipitated by acetonitrile and amoxicillin concentrations in sputum were determined by HPLC coupled with tandem-mass spectrometry. Following liquid extraction with ethyl acetate, cotrimoxazole was quantified by HPLC using ultraviolet detection. Both methods were rapid, specific, accurate and reproducible. The method was applied to patient samples. In three treated patients, concentrations of amoxicillin in sputum were similar and below the lower limit of quantification (0.1 μg/g) and in six patients, sputum concentrations up to 11.1 and 6.4 μg/g were measured for sulfamethoxazole and trimethoprim, respectively.

Topics: Amoxicillin; Chromatography, High Pressure Liquid; Cystic Fibrosis; Drug Monitoring; Humans; Limit of Detection; Linear Models; Reproducibility of Results; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination

Burkholderia cepacia complex (BCC) is an emerging pathogen of nosocomial infection in chronic or critically ill patients without cystic fibrosis (CF). The objective was to evaluate the management and outcomes of BCC bacteremia in patients without CF. We conducted a retrospective study of non-CF adult patients with BCC bacteremia between January 1997 and December 2016 at 4 tertiary hospitals in South Korea. A total of 216 non-CF patients with BCC bacteremia were identified. Most cases were hospital-acquired (79.2%), and the most common source was a central venous catheter (CVC) (42.1%). The rates of susceptibility to trimethoprim-sulfamethoxazole and piperacillin-tazobactam of BCC isolates were high as 92.8% and 90.3%, respectively. The rates of susceptibility to ceftazidime, meropenem, and levofloxacin were 75.5%, 72.3%, and 64.1%, respectively. The 14-day, 30-day, and in-hospital mortality rate was 19.4%, 23.1%, and 31.0%, respectively. Female (OR = 3.1; 95% CI, 1.4-6.8), liver cirrhosis (OR = 6.2; 95% CI, 1.6-16.6), septic shock (OR = 11.2; 95% CI, 5.1-24.8), and catheter-related infection (OR = 2.6, 95% CI, 1.2-5.8) were the independent risk factors for 30-day mortality. The outcome did not differ according to type of antibiotics used. Among 91 patients with CVC-related BCC bacteremia, delayed CVC removal (> 3 days) had a higher rate of persistent bacteremia (54.5 vs. 26.1%; P = 0.03) and lower rate of clinical response (49.0 vs. 71.9%; P = 0.04), compared with early CVC removal (within 3 days). BCC bacteremia occurring in non-CF patients was mostly hospital-acquired and CVC-related. Early removal of the catheter is crucial in treatment of CVC-related BCC bacteremia.

Topics: Aged; Bacteremia; Burkholderia cepacia complex; Burkholderia Infections; Catheter-Related Infections; Cystic Fibrosis; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Republic of Korea; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Chronic respiratory infection with

Topics: Administration, Inhalation; Administration, Oral; Anti-Bacterial Agents; Burkholderia cenocepacia; Burkholderia Infections; Child, Preschool; Cystic Fibrosis; Humans; Levofloxacin; Male; Maxillary Sinus; Maxillary Sinusitis; Meropenem; Nasal Lavage; Otorhinolaryngologic Surgical Procedures; Penicillins; Trimethoprim, Sulfamethoxazole Drug Combination

One of the most interesting features of

Topics: Cystic Fibrosis; Humans; Mutation; Phenotype; Staphylococcal Infections; Staphylococcus aureus; Thymidylate Synthase; Trimethoprim, Sulfamethoxazole Drug Combination

Infection with Burkholderia cepacia complex (Bcc) results in a heterogeneous clinical course ranging from asymptomatic colonization of the airways to fulminant respiratory failure in patients with cystic fibrosis (CF). Early eradication of Pseudomonas aeruginosa improves clinical outcomes. The efficacy and clinical outcomes following implementation of an eradication protocol for Bcc are less well understood.. We developed and implemented a single center Bcc eradication protocol that included an intensive combination of intravenous, inhaled, and oral antibiotic therapies based on in vitro sensitivities. We conducted a retrospective cohort analysis of clinical outcomes compared to patients with chronic Bcc infection.. Six patients were identified as having a newly acquired Bcc colonization and were placed on the eradication protocol. Sequential sputum samples after completion of the protocol demonstrated sustained clearance of Bcc in all patients. Lung function and nutritional status remained stable in the year following eradication.. Clearance of Bcc from sputum cultures using a standardized protocol was successful at one year and was associated with clinical stability.

Topics: Administration, Inhalation; Administration, Intravenous; Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Burkholderia cepacia complex; Burkholderia Infections; Ceftazidime; Clinical Protocols; Cohort Studies; Consolidation Chemotherapy; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Pneumonia, Bacterial; Retrospective Studies; Tobramycin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Burkholderia sp. infections are extremely complex in cystic fibrosis (CF) patients, especially considering the lack of knowledge regarding its behavior, its relationship with prognosis, as well as its transmissibility and multidrug resistance features. This study evaluated the frequency of chronic infection by Burkholderia, using microbiological and clinical data. Ninety-eight patients with CF attended from July 2011 to April 2014 in a Brazilian reference hospital were included. Antimicrobial activity, molecular epidemiology, Shwachman score, body mass index, exacerbations, and lung function were analyzed. Nine patients had chronic colonization, and all of them showed preserved pulmonary function levels, body mass index, and Shwachman score. Meropenem was the most effective antibiotic; however, divergent results were shown by other studies. Cross-contamination may have occurred in only two unrelated patients of different ages, who were colonized by B. vietnamiensis, which does not occur frequently. Twelve new sequence types (STs) were identified and three STs have presented intercontinental distribution. None of the patients presented known epidemic strains. In conclusion, a relatively low number of patients with chronic colonization and suspected cross-infection were identified. Different from other studies that have found CF patients chronically colonized with Burkholderia sp. having a greater deterioration of lung function, more frequent antibiotic therapy, and increased mortality, in the current study, the patients showed good clinical outcomes and favorable options for antibiotics therapy. This study also updated the epidemiological database, which facilitates the multicentric collaborative analysis and assists in the control of global infection by these pathogens.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Brazil; Burkholderia cepacia complex; Burkholderia Infections; Ceftazidime; Child; Child, Preschool; Cross Infection; Cystic Fibrosis; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals; Humans; Infant; Lung; Male; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Respiratory Function Tests; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Stenotrophomonas maltophilia, an opportunistic pathogen usually connected with healthcare-associated infections, is an environmental bacterium. Intrinsic resistance to multiple antibiotics, with different virulence determinants in the last decade classified this bacterium in the group of global multiple drug resistant (MDR) organism. S. maltophilia clinical isolates, were collected from tertiary care pediatric hospital in Belgrade, Serbia to investigate influence of different factors on biofilm formation, kinetics of biofilm formation for strong biofilm producers and effect of trimethoprim-sulfamethoxazole (TMP/SMX) on formed biofilm. Most of the isolates (89.8%) were able to form a biofilm. Analysis of biofilm formation in different growth conditions showed that changing of temeperature and pH had the stronggest effect on biofilm formation almost equally in group of cystic fibrosis (CF) and non-CF strains. TMP/SMX in concentration of 50 μg/ml reduced completely 24 h old biofilms while concentration of 25 μg/ml effects formed biofilms in a strain dependent manner. Among strains able to form strong biofilm CF isolates formed biofilm slower than non-CF isolates, while shaking conditions did not affect biofilm formation. Swimming motility was detected in both CF and non-CF isolates, however more motile strain formed stronger biofilms. This study suggests that temperature, pH and TMP/SMX had the strongest influence on biofilm formation in analyzed collection of S. maltophilia. A positive correlation between motility and strength of formed biofilm was demonstrated.

Topics: Anti-Bacterial Agents; Biofilms; Cross Infection; Cystic Fibrosis; Gram-Negative Bacterial Infections; Hospitals, Pediatric; Humans; Hydrogen-Ion Concentration; Microbial Sensitivity Tests; Serbia; Stenotrophomonas maltophilia; Temperature; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Burkholderia; Ceftazidime; Cystic Fibrosis; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Phylogeny; Protein Structure, Secondary; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardiosis is a rare disease with polymorphic presentations. The epidemiology and clinical presentation could change with the increasing number of immunocompromised patients.. The medical records and microbiological data of patients affected by nocardiosis and treated at the university hospitals of Marseille between 2004 and 2014 were analyzed retrospectively.. The cases of 34 patients infected by Nocardia spp during this period were analyzed. The main underlying conditions were transplantation (n=15), malignancy (n=9), cystic fibrosis (n=4), and immune disease (n=3); no immunodeficiency condition was observed for three patients. No case of AIDS was observed. At diagnosis, 61.8% had received steroids for over 3 months. Four clinical presentations were identified, depending on the underlying condition: the disseminated form (50.0%) and the visceral isolated form (26.5%) in severely immunocompromised patients, the bronchial form (14.7%) in patients with chronic lung disease, and the cutaneous isolated form (8.8%) in immunocompetent patients. Nocardia farcinica was the main species identified (26.5%). Trimethoprim-sulfamethoxazole was prescribed in 68.0% of patients, and 38.0% underwent surgery. Mortality was 11.7%, and the patients who died had disseminated or visceral nocardiosis.. The clinical presentation and outcome of nocardiosis depend on the patient's initial immune status and underlying pulmonary condition. Severe forms were all iatrogenic, occurring after treatments altering the immune system.

Topics: Adult; Aged; Chronic Disease; Cystic Fibrosis; Female; France; History, 21st Century; Hospitals, University; Humans; Immunocompromised Host; Male; Medical Records; Middle Aged; Neoplasms; Nocardia; Nocardia Infections; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Some bacterial species recovered from the airways of cystic fibrosis (CF) patients are indisputably associated with lung infections, whereas the clinical relevance of others, such as Nocardia spp., remains unclear. Sixteen French CF cases of colonization/infection with Nocardia spp. were reviewed in order to evaluate the epidemiology, the clinical impact and the potential treatment of these bacteria, and results were compared to those of the literature. Five Nocardia species were identified, Nocardia cyriacigeorgica being the major species (50 % of cases). At first isolation, Nocardia was the sole pathogen recovered in six patients. Seven patients presented pulmonary exacerbation. For 12 patients, antimicrobial treatment against Nocardia was started immediately, mainly based on cotrimoxazole (6 of the 12 cases). In this study, we highlight the heterogeneity of the clinical management of Nocardia spp. in CF. Guidelines for the clinical management of Nocardia infections in CF patients are proposed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Carrier State; Child; Child, Preschool; Cystic Fibrosis; France; Humans; Infant; Infant, Newborn; Male; Nocardia; Nocardia Infections; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

The purpose of this study was to characterize the utilization of antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations (PEx).. An anonymous national cross-sectional survey of CF Foundation accredited care programs was performed using an electronic survey tool.. Fifty-eight percent (152/261) CF Foundation accredited programs completed the survey. Ninety-eight percent (149/152) of respondents reported using antibiotics (oral or intravenous) against MRSA. Variability exists in the use of antibiotics amongst the programs and in the dosages utilized. For oral outpatient treatment, sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten percent of reported to use it in combination with rifampin. For inpatient treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized in both pediatric (IV 35/224, 16%; oral 41/224, 18%), and adult (IV 44/235, 19%; oral 38/235, 16%) respondents for inpatient treatment. IV vancomycin was the second most commonly utilized antibiotic by pediatric (70/224, 31%) and adult (71/235, 30%) respondents. Most respondents reported dose titration to achieve a vancomycin trough level of 15-20 mg/L (150/179, 84%). Topical or inhaled antibiotic utilization was reported to be an uncommon practice with approximately 70% of pediatric and adult respondents reporting to use them either rarely or never. The concomitant use of anti-MRSA and anti-pseudomonal antibiotics was common with 96% of pediatric and 99% of adult respondents answering in the affirmative.. We conclude that anti-MRSA antibiotics are utilized via various dosage regimens by a majority of CF Foundation accredited care programs for the treatment of chronic MRSA in PEx, and there is no consensus on the best treatment approach.

Topics: Adult; Anti-Bacterial Agents; Child; Cross-Sectional Studies; Cystic Fibrosis; Drug Administration Schedule; Drug Therapy, Combination; Health Care Surveys; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Practice Patterns, Physicians'; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Pandoraea spp. are recently discovered bacteria, mainly recovered from cystic fibrosis (CF) patients, but their epidemiology and clinical significance are not well known. We describe an epidemic spread of Pandoraea pulmonicola from 2009 in our CF center, involving 6 out of 243 CF patients.. Bacterial identification used amplified ribosomal DNA restriction analysis (ARDRA), MALDI-TOF mass spectrometry (MALDI-TOF MS) and 16S rDNA gene sequencing. The clonal link between strains was assessed with pulsed field gel electrophoresis (PFGE) using XbaI. Clinical data were gathered for all patients.. The index case was chronically colonized since 2000. The main hypothesis for this bacterial spread was a droplet cross-transmission, due to preventive measures not being strictly followed. Antibiotic susceptibility testing revealed resistance to beta-lactams, ciprofloxacin and colistin. However, there was susceptibility to trimethoprim-sulfamethoxazole. All patients were chronically colonized with Pseudomonas aeruginosa, and the acquisition of P. pulmonicola resulted in chronic colonization in all patients. Three patients died, and two patients remained clinically stable, whereas one patient had a decline in lung function.. This study, which is the first to describe an epidemic spread of P. pulmonicola, notes the potential transmissibility of this bacterial species and the need for infection control measures.

Topics: Adolescent; Adult; Burkholderiaceae; Cystic Fibrosis; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gram-Negative Bacterial Infections; Humans; Infection Control; Male; Middle Aged; Pseudomonas aeruginosa; Restriction Mapping; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Ceftazidime is the only anti-pseudomonal beta-lactam that has been reported to be administered by extended infusion in pediatric cystic fibrosis (CF) patients. A small pediatric pharmacokinetic/pharmacodynamic study has been published regarding the use of intermittent extended infusion doripenem in the treatment of an acute pulmonary exacerbation (APE) in pediatric CF patients; however, clinical use of intermittent extended infusion doripenem in pediatric CF patients has not been previously reported. We present three cases administering intermittent extended infusion doripenem in pediatric CF patients for the treatment of an APE in the case of replacing meropenem due to shortage. The delivery of beta-lactam antibiotics via intermittent extended infusion should be considered in order to optimize the pharmacodynamics of beta-lactams in the treatment of an APE.

Topics: Adolescent; Anti-Bacterial Agents; Burkholderia cenocepacia; Burkholderia Infections; Carbapenems; Child; Cystic Fibrosis; Disease Progression; Doripenem; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Pseudomonas stutzeri; Rhodospirillaceae; Thienamycins; Tobramycin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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

There is an increase in the isolation of non-fermenting gramnegative bacilli in patients with cystic fibrosis (CF). The present study evaluates the frequency of isolates of Chryseobacterium spp., analyzing its characteristics, resistance patterns and clinical outcome of patients.. It has been collected all respiratory isolates of Chryseobacterium spp. of patients attended in the CF unit of Hospital de la Princesa for three years (march 2009-march 2012). For phenotypic and genotypic identification and sensitivity study conventional methodology was used. For the assessment of the patients lung function was considered the forced expiratory volume in one second (FEV1) and the results were analyzed with SPSS.. There was an increase in the incidence of Chryseobacterium spp. with 17 isolates from 9 patients. Three patients had chronic colonization by this microorganism and one showed significant impairment of lung function. Seven patients showed also colonization with Staphylococcus aureus and 4 of them with Pseudomonas aeruginosa.. Chryseobacterium spp. should be considered as a new emerging opportunistic pathogen in patients with CF. It is essential the clinical and microbiological monitoring of this group of patients for detection of Chryseobacterium spp. colonization and to prevent the chronic infection. In these circumstances it must assess its possible eradication, though its clinical impact is unknown. Cotrimoxazole being the best treatment option.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Chryseobacterium; Coinfection; Comorbidity; Cystic Fibrosis; Disease Susceptibility; Drug Resistance, Microbial; Flavobacteriaceae Infections; Forced Expiratory Volume; Genotype; Humans; Incidence; Lung; Opportunistic Infections; Phenotype; Pseudomonas Infections; Spain; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients undergo remarkable phenotypic divergence over time, including loss of pigmentation, hemolysis, motility, and quorum sensing and emergence of antibiotic hypersusceptibility and/or auxotrophism. With prolonged antibiotic treatment and steady decline in lung function in chronically infected patients, the divergent characteristics associated with CF isolates have traditionally been regarded as "adapted/unusual virulence," despite the degenerative nature of these adaptations. We examined the phenotypic and genotypic diversity in clonally related isogenic strains of P. aeruginosa from individual CF patients. Our observations support a novel model of intra-airway pseudomonal syntrophy and accompanying loss of virulence. A 2007 calendar year collection of CF P. aeruginosa isolates (n = 525) from 103 CF patients yielded in vitro MICs of sulfamethoxazole-trimethoprim (SMX-TMP, which typically has no activity against P. aeruginosa) ranging from 0.02 to >32 μg/ml (median, 1.5). Coisolation of clonally related SMX-TMP-susceptible and -resistant P. aeruginosa strains from the same host was common (57%), as were isogenic coisolates with mutations in efflux gene determinants (mexR, mexAB-oprM, and mexZ) and genes governing DNA mismatch repair (mutL and mutS). In this cohort, complete in vitro growth complementation between auxotrophic and prototrophic P. aeruginosa isogenic strains was evident and concurrent with the coding sequence mosaicism in resistance determinants. These observations suggest that syntrophic clonal strains evolve in situ in an organized colonial structure. We propose that P. aeruginosa adopts a multicellular lifestyle in CF patients due to host selection of an energetically favorable, less-virulent microbe restricted within and symbiotic with the airway over the host's lifetime.

Topics: Adaptation, Physiological; Anti-Bacterial Agents; Chronic Disease; Clone Cells; Cystic Fibrosis; Genes, Bacterial; Genetic Heterogeneity; Humans; Microbial Sensitivity Tests; Mosaicism; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (SXT), alone and in combination with rifampicin (RIF), is a therapeutic option against Staphylococcus aureus, including strains expressing meticillin resistance. However, the antimicrobial activity of SXT is antagonised by thymidine, which can be present in infected and/or inflamed tissues such as the airways of cystic fibrosis (CF) patients. In this study, thymidine concentrations in CF sputa were determined and the antimicrobial activities of SXT, 5-iodo-2'-deoxyuridine (IdUrd) and RIF alone and in combination against S. aureus were analysed. Thymidine concentrations in the sputa of ten different CF patients varied from <100 μg/L to 38845 μg/L. The abolished antimicrobial activity of SXT against 22 S. aureus strains in the presence of thymidine was restored by combination with IdUrd. In contrast, SXT combined with RIF in the presence of thymidine did not show a synergistic effect and, furthermore, allowed the emergence of RIF-resistant bacteria. Adding RIF to the combination of SXT and IdUrd did not improve antimicrobial activity against S. aureus. In conclusion, the combination of SXT and RIF as a therapeutic option against S. aureus infections in chronic inflamed tissues should be judged critically.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Cystic Fibrosis; Drug Interactions; Humans; Idoxuridine; Microbial Sensitivity Tests; Rifampin; Sputum; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (SXT)-resistant Staphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from the airways of cystic fibrosis (CF) patients, often in combination with isogenic normal strains if patients were treated with SXT for extended periods. As SXT inhibits the synthesis of tetrahydrofolic acid, which acts as a cofactor for thymidylate synthase (thyA), the survival of TD-SCVs depends exclusively on the availability of external thymidine. Since the underlying mechanism for thymidine dependency is unknown, we investigated if alterations in the thyA nucleotide sequences were responsible for this phenomenon. Sequence analysis of several clinical TD-SCVs and their isogenic normal strains with reference to previously published S. aureus thyA nucleotide sequences was performed. Three clinical TD-SCVs were complemented by transforming TD-SCVs with the vector pCX19 expressing ThyA from S. aureus 8325-4. Transcriptional analysis of metabolic and virulence genes and regulators (agr, hla, spa, citB, thyA, and nupC) was performed by quantitative reverse transcription-PCR. The previously published sequences of thyA and two normal clinical strains were highly conserved, while thyA of four normal strains and four SCVs had nonsynonymous point mutations. In 8/10 SCVs, deletions occurred, resulting in stop codons which were located in 4/10 SCVs close to or within the active site of the protein (dUMP binding). Complementation of TD-SCVs with thyA almost fully reversed the phenotype, growth characteristics, and transcription patterns. In conclusion, we demonstrated that mutations of the thyA gene were responsible for the phenotype of TD-SCVs. Complementation of TD-SCVs with thyA revealed that a functional ThyA protein is necessary and sufficient to change the SCV phenotype and behavior back to normal.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Culture Media; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Mutation; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Staphylococcal Infections; Staphylococcus aureus; Thymidine; Thymidylate Synthase; Trimethoprim, Sulfamethoxazole Drug Combination

Thymidine-dependent small-colony variants (SCVs) of Staphylococcus aureus are frequently associated with persistent and recurrent infections in cystic fibrosis patients. The phenotypic appearance of S. aureus SCVs or normal-colony variants (NCVs) is postulated to be affected by the intracellular amount of dTMP. This hypothesis was proven by metabolic pathway assays revealing altered intracellular dTMP concentrations, followed by investigation of the associated phenotype. Inhibition of the staphylococcal thymidylate synthase, which generated intracellular dTMP from dUMP, using 5-fluorouracil and co-trimoxazole resulted in an SCV phenotype. Inhibition of a nucleoside transporter, which provided the bacterial cell with extracellular thymidine, caused growth inhibition of SCVs. In turn, reversion of SCVs to NCVs was achieved by supplying extracellular dTMP. High-performance liquid chromatography additionally confirmed the intracellular lack of dTMP in SCVs, in contrast to NCVs. Moreover, the dTMP concentration is postulated to influence the intracellular persistence of S. aureus. Cell culture experiments with cystic fibrosis cells revealed that clinical and co-trimoxazole-induced SCVs with a diminished amount of dTMP showed significantly better intracellular persistence than NCVs. In conclusion, these results show that the dTMP concentration plays a key role in both the phenotypic appearance and the intracellular persistence of S. aureus.

Topics: Anti-Bacterial Agents; Cell Line; Cystic Fibrosis; Dihydropteroate Synthase; Fluorouracil; Folic Acid Antagonists; Humans; Lung; Phenotype; Staphylococcus aureus; Thymidine; Trimethoprim, Sulfamethoxazole Drug Combination; Uridine

Cystic fibrosis (CF) patients are predisposed to chronic respiratory infection by nonfermentative gram-negative bacilli, including Stenotrophomonas maltophilia. S. maltophilia is highly resistant to most antibiotics, with the exception of sulfamethoxazole-trimethoprim (SXT). SXT-resistant S. maltophilia has been reported, but the mechanism of resistance is not well defined. Repeated findings of suspected small-colony-variant (SCV) S. maltophilia isolates from the sputa of five CF patients were confirmed by partial 16S rRNA gene sequencing. The SCV S. maltophilia isolates were the only S. maltophilia isolates in these cultures, and none were clonally related. DNA fingerprint analysis confirmed that once established, the SCV S. maltophilia strains persisted. Nutritional studies of SCV S. maltophilia have suggested auxotrophy in hemin, methionine, and thymidine associated with resistance to multiple antibiotics, including SXT. The phenotypic switch from wild-type to SCV S. maltophilia was reproducible in vitro by exposure to SXT, suggesting that prolonged exposure to antibiotics may select for both the SCV S. maltophilia phenotype and SXT resistance by interference with the dihydrofolate reductase pathway. Recovery of SCV S. maltophilia from the sputum of CF patients has implications for both laboratory testing and patient management.

Topics: Anti-Bacterial Agents; Culture Media; Cystic Fibrosis; DNA Fingerprinting; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Phenotype; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Sputum; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Cystic Fibrosis; Humans; Lung Transplantation; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bronchoalveolar Lavage Fluid; Child, Preschool; Cystic Fibrosis; Fever; Humans; Male; Nocardia asteroides; Nocardia Infections; Pneumonia, Bacterial; Prognosis; Recurrence; Risk Assessment; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Herein we report a case of a cystic fibrosis child who was simultaneously infected with Burkholderia cepacia genomovar III and Burkholderia vietnamiensis. After antimicrobial therapy only B. cepacia genomovar III persisted.

Topics: Amikacin; Anti-Infective Agents; Burkholderia; Burkholderia cepacia complex; Burkholderia Infections; Ciprofloxacin; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Infant; Male; Respiratory Tract Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Our purpose was to characterize the decisive pathophysiologic factors that lead to renal stone formation (nephrolithiasis) in patients with cystic fibrosis (CF).. Patients with CF (n = 96) were investigated with respect to lithogenic and inhibitory factors of urolithiasis and compared with 30 healthy control patients. They were subdivided into 2 groups, 86 without renal stones and 10 with renal stones.. All stones were exclusively composed of calcium oxalate. As a major pathogenic factor, a urinary disequilibrium between promoting and inhibitory components of stone formation, characterized mainly by hypercalciuria, hyperoxaluria, and hypocitraturia, was found in the patients with nephrolithiasis. They tended to have lower plasma phosphate concentrations and an increased urinary phosphate excretion. The citrate/calcium ratio proved to be a valuable means to discriminate patients with renal stones from control patients. Patients with stones had ingested more cotrimoxazole and ceftazidim, cumulatively, than patients without stones. There was an inverse correlation between the amounts of antibiotics ingested and the percentage of tubular phosphate reabsorption (r = -0.91, P <.0046).. Renal stone formation in patients with CF is caused by a disequilibrium between promoting and inhibitory components of stone formation, which is dominated by hypercalciuria, hyperoxaluria, and hypocitraturia. Treatment with cotrimoxazole and ceftazidim, primarily, may lead to renal proximal tubular damage with an ensuing sequence of phosphate loss, increase of parathyroid hormone secretion, increased 1,25-dihydroxyvitamin D3 formation, and absorptive hypercalciuria.

Topics: Adolescent; Adult; Anti-Infective Agents; Ceftazidime; Cephalosporins; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Kidney Calculi; Kidney Tubules; Male; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Over a 7-year period, three patients with cystic fibrosis had multiple sputum specimens that were smear- and culture-positive for Nocardia asteroides. Two of the patients had received long-term, low-dose inhalational corticosteroid therapy. Although all three patients were treated with cotrimoxazole, resulting in eradication of the organism from the sputum, there was no change in their clinical state, radiological findings, or pulmonary function. The isolation of Nocardia asteroides from the respiratory tract of cystic fibrosis patients is an unusual finding. Its presence does not necessarily imply disease, and in these three cases, it most likely represented colonisation. The clinical significance of Nocardia spp. isolated from the respiratory tract of cystic fibrosis patients needs to be considered in the context of the individual clinical picture.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Carrier State; Cystic Fibrosis; Female; Humans; Immunosuppressive Agents; Male; Nocardia asteroides; Nocardia Infections; Trimethoprim, Sulfamethoxazole Drug Combination

In September 1997, a 25-year-old Italian woman with cystic fibrosis (CF) spent 3 weeks in Thailand. In August 1998, her pulmonary function rapidly declined, with productive cough and intermittent fever. Chest x-ray films revealed diffuse, small, patchy opacities in the upper lobes. Burkholderia pseudomallei (BP) was isolated from specimens of the patient's sputum and was identified by means of 16S rDNA sequencing. The diagnosis of melioidosis was serologically confirmed. Continuous therapy with ceftazidime and co-trimoxazole and maintenance with co-trimoxazole, doxycycline, and chloramphenicol resulted in eradication of BP. We present the issue of whether patients with CF represent a population particularly at risk for melioidosis.

Topics: Anti-Bacterial Agents; Burkholderia pseudomallei; Ceftazidime; Cephalosporins; Cystic Fibrosis; DNA, Bacterial; Drug Therapy, Combination; Female; Humans; Melioidosis; Molecular Sequence Data; Risk Factors; RNA, Ribosomal, 16S; Thailand; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

SUMMARY. Continuous therapy with antistaphylococcal antibiotics is advocated by some cystic fibrosis (CF) centers, but it is unclear whether this strategy favors early colonization with P. aeruginosa. We used the data base for the German Centers of the European Registry for Cystic Fibrosis (ERCF) to assess the effect of continuous antistaphyloccocal therapy on the rate of P. aeruginosa acquisition in CF patients. Patients included in this analysis had to be < 18 years of age, P. aeruginosa-negative prior to entry in the ERCF, and to have had at least 2 additional P. aeruginosa-negative respiratory cultures while followed in the ERCF. Of the 639 patients fulfilling these criteria, 48.2% received continuous antistaphyloccocal therapy, 40.4% intermittent antibiotic therapy, and 11.4% no antibiotic therapy. There were no differences between the groups in body mass index, as well as forced vital capacity (FVC) and forced expired volume in 1 sec (FEV(1)) at baseline. The rate at which patients acquired positive respiratory cultures for Staph. aureus was significantly lower in the group receiving continuous antistaphyloccocal antibiotic therapy than in those not receiving such therapy. Patients receiving continuous antistaphyloccocal antibiotic therapy had a significantly higher rate of P. aeruginosa acquisition compared to patients receiving only intermittent or no antibiotic therapy. This difference was especially apparent for children younger than age 6 years. We conclude that continuous therapy with antistapyloccocal antibiotics directed against Staph. aureus increases the risk of colonization with P. aeruginosa. How this affects the clinical outcome of these patients remains to be determined.

Topics: Adolescent; Anti-Bacterial Agents; Body Mass Index; Cephalosporins; Chemoprevention; Child; Child, Preschool; Cystic Fibrosis; Databases as Topic; Forced Expiratory Volume; Humans; Infant; Lung; Macrolides; Pseudomonas aeruginosa; Pseudomonas Infections; Registries; Staphylococcal Infections; Staphylococcus aureus; Statistics, Nonparametric; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vital Capacity

Topics: Adult; Cystic Fibrosis; Fatal Outcome; Gram-Negative Bacterial Infections; Humans; Male; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

In an effort to develop new strategies, the authors are exploring the hypothesis that non-anti-Pseudomonas aeruginosa antibiotics can affect some major virulence factors in cystic fibrosis P. aeruginosa. Recent samples (127) of P. aeruginosa isolated from the sputum of cystic fibrosis patients and manifesting a mucoid growth were stored at -70 degrees C until experimentation. The mucoid character was retested after thawing and one 24-h in-vitro passage at 37 degrees C onto 100-mm blood agar plates to prepare a bacterial suspension for inoculation (Steers or MIC-2000 plus replicator) and cultivation (48 h, 37 degrees C) onto different 100-mm or 150-mm Mueller-Hinton agar plates containing either no antibiotics or antibiotics alone, and antibiotic combinations without presumed anti-P. aeruginosa activity. Some isolates (49, 38.6%) of P. aeruginosa expressed again the mucoid character on antibiotic-free Mueller-Hinton agar and growth was prevented by antibiotics in a number of them: 7 with doxycycline (16.0 micrograms/ml), 2 with rifampicin (16.0 micrograms/ml), 6 with roxithromycin-sulfamethoxazole (16.0-304.0 micrograms/ml) and 23 with trimethoprim-sulfamethoxazole. In the remaining evaluable isolates, the mucoid was modified towards the rough character in 36 out of 42 with doxycyline, 36 out of 47 with rifampicin, 31 out of 43 with roxithromycin-sulfamethoxazole and 20 out of 26 with trimethoprim-sulfamethoxazole. In parallel, the pigmentation was lost in the presence of antibiotics in those P. aeruginosa isolates having manifested this character on Mueller-Hinton agar. These results suggest that non-anti-P. aeruginosa antibiotics can modify the in vitro markers of virulence in cystic fibrosis P. aeruginosa and that they merit further investigation.

Topics: Anti-Bacterial Agents; Cystic Fibrosis; Doxycycline; Drug Combinations; Humans; Leucomycins; Pigmentation; Pseudomonas aeruginosa; Rifampin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virulence

During a 1-year period, the prevalence of thymidine-dependent (TD) Staphylococcus aureus in patients at two geographically distinct cystic fibrosis (CF) centers was determined. Of 200 CF patients who had their respiratory secretions cultured, 95 harbored S. aureus, and 20 (21%) had TD S. aureus as their predominant staphylococcal isolate. All 20 TD S. aureus-positive patients had received trimethoprim-sulfamethoxazole for an average of 30.9 months. It was also observed that TD S. aureus exhibited aberrant colony morphologies or did not grow on media commonly used in CF centers for S. aureus isolation, suggesting that this organism could be missed by routine culture methods. In contrast, all 20 isolates had typical staphylococcal morphology on mannitol salt agar after 48 h of incubation. Mannitol salt agar is recommended for primary isolation of TD S. aureus.

Topics: Culture Media; Cystic Fibrosis; Drug Combinations; Humans; Respiratory System; Staphylococcus aureus; Sulfamethoxazole; Thymidine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Cystic Fibrosis; Drug Combinations; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The first-dose and steady-state pharmacokinetics of trimethoprim and sulfamethoxazole were determined in 14 patients with cystic fibrosis. When pharmacokinetic data from the first dose were compared with those at steady state, both TMP and SMZ showed expected accumulations in serum concentrations and decreases in total body clearance. The area under the SMZ serum concentration-time curve was significantly greater at steady state, suggesting drug accumulation during long-term therapy. When pharmacokinetic characteristics for TMP and SMZ obtained in patients with cystic fibrosis were compared with those reported for normal adults, the patients were found to have shorter elimination half-lives and greater plasma clearances. In addition, the apparent volume of distribution for TMP was smaller for patients with cystic fibrosis than for normal adults, consistent with their reduced mass of adipose tissue. Our data support the need for increased dosing or decreased dosing intervals when administering TMP-SMZ to patients with cystic fibrosis.

Topics: Adolescent; Adult; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Female; Humans; Kinetics; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Fourteen patients with cystic fibrosis received 18 treatment courses with ceftazidime for acute respiratory illnesses associated with Pseudomonas cepacia. All patients had severe chronic lung disease. Clinical improvement occurred in only six treatment courses; eight treatment courses resulted in failure and four patients died. Severe illness was characterized by high fever, marked elevation of WBC and ESR. Treatment had no effect on sputum colony counts of Ps. cepacia in 17 of 18 courses, but significantly reduced counts of Ps. aeruginosa in 90% of those patients infected with both bacteria.

Topics: Adolescent; Ceftazidime; Cephalosporins; Cystic Fibrosis; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Piperacillin; Pseudomonas Infections; Respiratory Tract Infections; Sulfamethoxazole; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In respiratory tract infections in children a distinction must be made between frequently recurring infections and genuine chronic infections due to specific anatomical factors, immunological defects or congenital diseases such as mucoviscidosis. The most frequent pathogens are Haemophilus influenzae, pneumococci, Staphylococcus aureus, Streptococcus pyogenes, enterococci, Pseudomonas aeruginosa and Klebsiella, S. aureus predominates in infants. The same applies for mucoviscidosis, in which P. aeruginosa is the second most frequent pathogen, occurring frequently after a primary infection with staphylococci. In order to avoid frequent relapses in mucoviscidosis patients, uninterrupted long-term treatment with an antibiotic which is effective against staphylococci is recommended, commencing the moment the diagnosis has been established. Suitable antibiotics are co-trimoxazole or oral cephalosporins (e. g. cephalexin, cephradine or cefaclor). Other respiratory tract infections should be treated according to the antibiogramme with a suitable antibiotic once the diagnosis has been confirmed.

Topics: Cephalosporins; Child; Child, Preschool; Cystic Fibrosis; Drug Combinations; Humans; Infant; Infant, Newborn; Long-Term Care; Pseudomonas Infections; Recurrence; Respiratory Tract Infections; Staphylococcal Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination