Successful use of daptomycin in Panton-Valentine leucocidin positive Staphylococcus aureus paediatric osteomyelitis

IntroductionEfficacy of daptomycin has been recorded in adult Gram-positive bone and joint infections OAI (1) and daptomycin has been used as secondary or tertiary agent when primary agents have failed (1, 2) in the treatment of osteoarticular infections caused by Staphylococcus aureus.Presentation of caseWe report a 16-year-old schoolboy with Panton-Valentine Leucocidin (PVL) positive methicillin susceptible S. aureus osteomyelitis, who was refractory to 9 days of recognised antimicrobial chemotherapy with progressive multifocal haematogenous spread. Subsequent addition of daptomycin promptly cleared the bacteraemia and arrested the disease process within 9 days.DiscussionAlthough cases have been reported of daptomycin usage in children with invasive staphylococcus bacteraemia, endocarditis and OAI (2), we believe this to be the first case report describing the use of daptomycin in paediatric osteomyelitis caused by PVL positive S. aureus.ConclusionRepercussions of osteomyelitis, in particular those caused by PVL S. aureus, and evolving resistance patterns internationally, highlight the need for further evaluation of daptomycin in the paediatric arena. The response seen with the addition of Daptomycin in this case suggests possible reduction in hospital stay and number of surgical procedures when compared to other published series using conventional antibiotic regimens.     

Determining potential of PMMA as a depot for rifampin to treat recalcitrant orthopaedic infections

BackgroundOpen fractures are often complicated by infection. In cases of severe soft tissue and vascular injury, systemic antibiotics may be ineffective due to their inability to reach and provide direct antimicrobial activity to the zone of injury. High antibiotic concentrations within the wound can be achieved with reduced systemic toxicity by using local antibiotic delivery. As bacteria associated with musculoskeletal injuries frequently form biofilms, antibiotic selection is important. Herein, the use of rifampin, an antibiotic with activity against biofilms, delivered via polymethylmethacrylate (PMMA) beads is evaluated for use in a traumatic musculoskeletal wound model.MethodsPMMA beads loaded with rifampin, or combinations of rifampin and vancomycin, were prepared and evaluated for time to curing, drug release kinetics in vitro, and infection prevention in vivo using a well-established rat model of musculoskeletal infection. A segmental bone defect was created and contaminated with methicillin susceptible Staphylococcus aureus (UAMS-1). Wounds were debrided, irrigated, and treated with PMMA beads, containing rifampin or combinations of rifampin plus vancomycin, following a 6-h (early) or 24-h (delayed) treatment. After 14 days, tissue, implants, and beads were removed for bacterial quantification and assessed for rifampin resistance.ResultsThere was a direct association between loaded concentration and release kinetics of the rifampin and vancomycin from PMMA beads. Higher rifampin concentrations delayed PMMA curing times. The addition of vancomycin to PMMA resulted in more rapid release of rifampin from beads. However, the highest concentration of rifampin loaded PMMA beads (10% wt/wt) was the only treatment to significantly reduce bacterial counts. No rifampin resistance was observed.ConclusionAlthough higher concentrations of rifampin resulted in significant reductions of bacteria, these levels extended PMMA curing times and transformed PMMA material characteristics. While these characteristics make the material unsuitable for weight-bearing applications, such as total joint arthroplasty, the use of rifampin-loaded PMMA beads may be an effective intervention in a contaminated traumatic extremity wound due to its ability to eradicate biofilms.     

A cohort study of the Copenhagen CF Centre eradication strategy against Staphylococcus aureus in patients with CF

BackgroundStaphylococcus aureus is an important pathogen in CF. Centre prevalence of intermittent colonization and chronic S. aureus infections and the effectiveness of an anti-S. aureus eradication strategy was assessed.MethodsAll airway cultures from 300 patients in a 2-year period were retrieved and all anti‐S. aureus antibiotic treatments were evaluated for treatment success. Chronic infection was defined as a positive culture of S. aureus in 50% or more of the months each year. Change in FEV₁ following 2 weeks of treatment of S. aureus was assessed in clinically stable patients. Primary outcome was S. aureus eradication at next clinical visit and number of patients chronically infected.ResultsThe yearly prevalence of S. aureus intermittent and chronic infection was 47% and 14%, respectively. Eradication was successful at the next clinical visit in 61% of the standard treatment and 53% of the prolonged treatments, respectively. FEV₁ improved significantly following anti-S. aureus treatment (3.3%, p < 0.0001).ConclusionOur anti-S. aureus eradication strategy in CF patients resulted in a low prevalence of chronic infections and high treatment efficacy. Furthermore, anti-staphylococcal treatment may be associated with a short-term improvement in lung function.     

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) infection is increasingly common. Treatment with vancomycin-based therapy is often unsuccessful. Daptomycin is a relatively new lipopeptide antibiotic with potent activity against MRSA.PurposeTo describe the successful management of MRSA infection involving the spine.Study designTwo case reports of MRSA infection, one involving epidural and lumbar subdural abscesses, the other with osteomyelitis and discitis.MethodsTwo cases are described, one with lumbar epidural and subdural abscesses and the other with osteomyelitis and discitis of the spine. Switching from vancomycin to daptomycin plus rifampin-based therapy resulted in patient improvement that allowed discharge from the hospital.ResultsBoth patients recovered fully from their infection.ConclusionsDaptomycin is a safe and effective option for the treatment of MRSA infection involving the spine.     

Prevention of Vascular Graft Infections with Antibiotic Graft Impregnation Prior to Implantation: In Vitro Comparison between Daptomycin,Rifampin and Nebacetin

ObjectiveTo compare the in vitro efficacy of graft impregnation with nebacetin versus rifampin versus daptomycin against vascular graft infections caused by Staphylococcus epidermidis and Staphylococcus aureus and nebacetin versus rifampin against Pseudomonas aeruginosa and Escherichia coli.MaterialsTwenty-three Dacron-grafts (1 cm²) for each micro-organism were microbiologically tested and eight grafts per antibiotic underwent viability tests against human umbilical vein endothelial cells (ECs). Fifteen grafts (5/antibiotic agent) underwent 15 min impregnation and contamination with 4 ml bacterial solution (optical density (OD_600 nm): 0.20 ± 0.02). After 24-h-incubation, all grafts were washed with phosphate-buffered saline and underwent sonification to release viable adherent bacteria. OD_600 nm of the solution was measured. Afterwards, six 1:10 dilution steps took place and colony-forming units (CFUs) were counted.ResultsNebacetin showed comparable efficacy to daptomycin against Gram-positive bacteria. Both eradicated more efficiently S. epidermidis than rifampin (daptomycin:0, rifampin:5 ± 7.3, nebacetin:0 CFU ml^?1, P = 0.0003). All antibiotics showed comparable antibacterial activity against S. aureus. Nebacetin was more efficient than rifampin to eradicate Gram-negative organisms (P. aeruginosa: rifampin:1308 ± 252, nebacetin:8 ± 8 CFU ml^?1, P = 0.01, E. coli: rifampin:294 ± 159, nebacetin:0.2 ± 0.5 CFU ml^?1, P = 0.001), while only rifampin was toxic against ECs (daptomycin:30.88 ± 5.44, rifampin:5.13 ± 5.08, nebacetin:28.50 ± 3.82 ECs/field, P = 0.0003).ConclusionsNebacetin showed excellent in vitro antibacterial activity against both Gram-positive and -negative pathogens representing an effective candidate for vascular graft impregnation.     

A network meta-analysis of the efficacy of inhaled antibiotics for chronic Pseudomonas infections in cystic fibrosis

BackgroundVarious 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.MethodsIn 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 (FEV₁) % predicted, P. aeruginosa sputum density and acute exacerbations.ResultsThe 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).ConclusionWe conclude that all studied antibiotics have comparable efficacies for the treatment of chronic P. aeruginosa lung infection in CF.     

Antibacterial activity,antibiotic retention,and infection resistance of a rifampin-impregnated gelatin-sealed Dacron graft

Purpose: A gelatin-sealed porous Dacron graft impregnated with rifampin was evaluated in a two-part study of its use in preventing prosthetic infection.Methods: The graft was impregnated by soaking it for 15 minutes in rifampin (1 mg/ml). In part 1 its antibacterial activity and rifampin retention over time were determined. Infrarenal aortic replacement was performed in pigs, and the rifampin concentration of the graft, serum, and perigraft space was assayed up to 96 hours after surgery. In part 2, infection resistance was tested in pigs in which the retroperitoneum was contaminated with Staphylococcus aureus after graft replacement. The postoperative infection rate was compared in three groups: pigs given gelatin-sealed grafts without rifampin (controls), pigs receiving nonimpregnated grafts and intravenous rifampin (15 mg/kg) for 3 days after surgery, and those given the rifampin grafts.Results: Rifampin was present in the grafts for up to 72 hours after surgery and in the perigraft fluid for 24 hours but was never detected in the serum. The grafts had inhibitory activity in vitro against S. aureus and the biofilm phase of Staphylococcus epidermidis for up to 3 days and against Escherichia coli for 2 days. Pigs given intravenous rifampin had a significantly lower infection rate than had control pigs (7/12 vs 13/13; p = 0.02); those receiving the rifampin graft had a lower rate (2/13) than had either the control pigs (p < 0.001) or those given intravenous rifampin (p < 0.04).Conclusions: This simple method of graft impregnation resulted in antibiotic retention for 3 days and appeared to be superior to intravenous antibiotic administration in preventing perioperative graft infection. (J VASC SURG 1994;19:675-82.)     

Deep infection after hip fracture surgery: predictors of early mortality

IntroductionThis study analysed the predictors of mortality in patients who are diagnosed with deep infection following hip fracture surgery.MethodsData were prospectively collected for 3 years from all patients undergoing hip fracture surgery and who had developed a subsequent deep infection. Infection was defined as positive microbiology culture from deep tissue or fluid samples. Demographic data, treatment, complications and subsequent surgeries were analysed. Potential predisposing factors including chronic medical co-morbidities, American Society of Anesthesiologists (ASA) grade, alcohol excess and smoking were assessed. The main outcome measures were 30-day and 1-year mortality.ResultsThere were 2718 consecutive operations performed for a fracture of the proximal femur over a 3-year period. Forty-three (1.6%) patients had a deep postoperative infection diagnosed on fluid and/or tissue sampling. The mean age was 73 years (25–94) and 65% were female. Of the 43 patients who developed deep infection, the primary procedure in 25 (58%) patients was reduction and internal fixation, with 18 (42%) undergoing hemi-arthroplasty. The most common causative organism was Staphylococcus epidermidis (n = 13, 30%), with methicillin-resistant Staphylococcus aureus (MRSA) accounting for 23% (n = 10). The 30-day mortality was significantly higher than that of patients with no deep infection (19% vs. 6.5%; p = 0.004). On univariate analysis, increasing age, dementia and diabetes were predictive of both 30-day and 1-year mortality (all p < 0.05). S. aureus (sensitive or resistant) was approaching significance at 1 year (p = 0.065). On multivariate analysis, dementia and diabetes were independent predictors of 30-day mortality, with dementia and S. aureus predictive at 1 year.ConclusionsThe 30-day mortality rate in patients diagnosed with deep infection following hip fracture surgery is higher than those without infection. Dementia, diabetes and S. aureus infection are independent predictors of mortality following deep infection.     

The effect of presence of facultative bacteria species on semen and sperm quality of men seeking fertility care

IntroductionInfections of male urogenital tracts may contribute to male infertility. However, the effects of bacterial presence on sperm quality and fertility are controversial.ObjectivesWe investigated the occurrence of non-specific bacteria and quality/quantity of semen of infertile and fertile control groups in Nigeria.Subjects and methodsWe investigated 162 infertile and 54 fertile men. Spermiogram, culture, bacterial isolation and characterization were conducted.ResultsWe report 114/162(70.4%) occurrence of bacteria species, 49.4% of such were Gram positive and 21% Gram negative: Staphylococcus aureus (29.6%) and Escherichia coli (10.5%) had the highest occurrence for each group respectively. On semen quality/quantity, we report 14.2% azoospermia, 52.5% oligozoospermia and 33.3% of normozoospermia. The mean sperm concentrations were 10 × 7/ml and 41 × 10 6/ml for oligo and normozoospermia respectively. Majority (52%) of azoospermic group had no bacterial growth. S. aureus was the most implicated among the bacterial positive group. Within the ologozoospermic category, 28% had no bacterial growth, 28% had S. aureus and 11.8% E. coli. The normozoospermic patients had 18.5% no bacteria contamination, 33.3% had S. aureus, 13% had E. coli. From the analysis, the normozoospermic group with bacterial contamination had lower sperm concentrations compared with those without contamination. It was apparent that factors other than bacterial contamination may contribute more to oligozoospermia (compare: “no bacteria” group mean sperm concentration 8.97 × 106/ml, Gram positive bacteria contaminated group 17.74 × 106/ml and Gram negative bacteria contaminated group 13.66 × 106/ml). The mean progressive motility ratios were lower (15.6 [a]% + 18.3 [b]%) = 33.9%) against WHO standard (a + b = >50%) and control RPM (a) = 55.3%. Generally, the semen quality (vol., rapid progressive motility, sperm concentration and immotility) were significantly lower than the fertile group, P = 0.0005, <0.0001, <0001 and 0.0335, respectively.ConclusionsAlthough bacterial presence in semen reduced mean sperm concentration and viability, thereby contributed to oligozoospermia and by extension the chances of siring a child, however, factors other than bacterial presence may contribute more. Improved interpretative approaches of semen analyses are highlighted.     

The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant

BackgroundOrthopaedic surgery is associated with unacceptable infection rates that respond poorly to systemic antibiotics. The objective of this study was to use an animal model for orthopaedic implant infection to examine the ability of a new-generation fibrin tissue sealant to effectively deliver antibiotics to the surgical site.MethodsThe antibiotics cefazolin, fusidic acid or 5-fluorouracil were blended into Vitagel? tissue sealant. The release rate of the drugs was measured using HPLC methods and bioactivity was measured by the zone of inhibition method with pathogenic Staphylococcus aureus. The antibiotic activity of the drug-loaded sealant was then tested in rats using infected orthopaedic surgical sites (titanium clip on spine). Efficacy was evaluated by residual bacterial counts on clips, clinical observations of infection, and histological findings.ResultsThe drugs were released in a controlled manner over 2–4 days. All three antibiotics demonstrated strong antibacterial activity when released from the sealants. None of the treated animals demonstrated systemic illness. Post mortem dissection revealed a well-encapsulated abscess surrounding the titanium clip with erosion of the bony process. Using an inoculum of 1–5 × 10³ CFU, treatment with antibiotic-loaded fibrin sealant demonstrated reduced infective swelling and reduced bacterial counts on surgical clip swabs compared to control rats or rats treated with antibiotic only. This model allowed for almost 100 % infectivity with a 0 % mortality rate due to infection, mimicking the clinical features of human implant infection.ConclusionThe results support the use of antibiotic-loaded commercially available fibrin sealants to prevent infection after implant surgery.     

Impact of selective antimicrobial agents on staphylococcal adherence to biomedical devices

BACKGROUND: Infection of intravascular or implanted biomedical devices often involves biofilm-forming staphylococci that are recalcitrant to antimicrobial therapy. The present study investigated the activity of 6 antimicrobial agents against biofilm-forming and non-biofilm-forming strains of staphylococci adherent to the surface of selected biomedical devices. METHODS: Five clinical staphylococcal strains were selected for study in (1) antibiotic-lock model (ALM) and (b) vascular graft model (Dacron and expanded polytetrafluoroethylene [ePFTE]) devices. Test strains were inoculated for 30 minutes to stabilize microbial adherence and then exposed to antibiotic; the impact on bacterial adherence was assessed at 1, 2, 4, 7, and 10 days. RESULTS: Regarding ALM, daptomycin and rifampin were effective at eradicating staphylococcal adherence by day 4 (P<.01); linezolid and gentamicin by day 7 (P<.01); vancomycin by day 7; and ceftriaxone failed to eradicate staphylococcal adherence in 4 of 5 strains by day 10. Regarding ePTFE, daptomycin and linezolid eradicated staphylococcal adherence by day 2 (P<.01); rifampin by day 4 (P<.01); vancomycin and gentamicin by day 7 (P<.01); and ceftriaxone failed to eliminate staphylococcal adherence in 3 of 5 strains by day 10. Regarding Dacron, daptomycin and rifampin eradicated adherent strains by day 4 (P<.01); linezolid by day 7 (P<.01), and vancomycin, gentamicin, and ceftriaxone decreased staphylococcal adherence by 90%, 95%, and 78%, respectively, by day 10. COMMENTS: Daptomycin, rifampin, and linezolid demonstrated greater efficacy and speed in eradicating microbial adherence of staphylococcal isolates from selected devices compared with vancomycin, gentamicin, or ceftriaxone (P<.01). Further studies are warranted, however, to validate the clinical efficacy of daptomycin and linezolid in the treatment of biomedical device-associated infections.     

Early discontinuation of tofacitinib in patients with rheumatoid arthritis co-treated with rifampin for latent tuberculosis

ObjectiveRifampin is known to influence the pharmacokinetics of tofacitinib owing to drug interactions. The aim of this study was to determine the efficacy of tofacitinib on co-administration with rifampin in rheumatoid arthritis (RA) patients.MethodsBiologic-naïve RA patients treated with tofacitinib were selected, and electronic medical reports were reviewed retrospectively. All patients underwent screening for latent tuberculosis infection (LTBI) before starting tofacitinib, and patients with positive results were treated to prevent progression to active tuberculosis. To evaluate the efficacy of tofacitinib with or without rifampin, the discontinuation rates of tofacitinib were examined during the first 6 months. Kaplan–Meier analysis was used to construct cumulative discontinuation curves, and comparisons were performed using the log-rank test.ResultsAmong 81 patients who starting tofacitinib, 21 were LTBI-positive and 18 were administered rifampin concomitantly with tofacitinib. Additionally, 14 of the 81 patients (17.3%) discontinued tofacitinib during the follow-up, and 7 patients discontinued tofacitinib because of uncontrolled RA activity. The discontinuation rates of tofacitinib within the first 6 months were significantly higher in patients treated with rifampin for LTBI than in those not treated with rifampin (lack of efficacy: 24.7% vs. 5.1%, P < 0.01; all causes: 38.9% vs. 11.2%, P < 0.01).ConclusionsDiscontinuation rates were higher in RA patients who started tofacitinib during chemoprophylaxis involving rifampin than in those who did not receive rifampin. Physicians should be aware that the efficacy of tofacitinib could be decreased by chemoprophylactic regimens for tuberculosis.     

Prevalence of cystic fibrosis pathogens in the oropharynx of healthy children and implications for cystic fibrosis care

ObjectiveTo describe the prevalence of the CF pathogens Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae in OP cultures from healthy children.MethodsOropharyngeal (OP) swabs were collected from 100 healthy children ≤ 18 years of age undergoing a clinically indicated procedure.ResultsP. aeruginosa was isolated from the OP swab of one participant, S. aureus from 48 participants (including 4 methicillin-resistant) and H. influenzae from 47 participants. Cultures from 75 participants grew one or more of these organisms (55 grew one, 19 grew 2 and one grew 3 organisms).ConclusionP. aeruginosa is rarely recovered from the oropharynx of healthy children ≤ 18 years of age, while recovery of S. aureus and H. influenzae is common. It is important to understand what the “normal” prevalence of CF pathogens is in the oropharynx in order to aid interpretation of OP cultures in CF patients.     

Molecular analysis of changes in Pseudomonas aeruginosa load during treatment of a pulmonary exacerbation in cystic fibrosis

BackgroundIntravenous antibiotics for pulmonary exacerbations (PEs) of cystic fibrosis (CF) usually target Pseudomonas aeruginosa. Insights into the CF lung microbiome have questioned this approach. We used RT-qPCR to determine whether intravenous antibiotics reduced P. aeruginosa numbers and whether this correlated with improved lung function. We also investigated antibiotic effects on other common respiratory pathogens in CF.MethodsSputa were collected from patients when stable and again during a PE. Sputa were expectorated into a RNA preservation buffer for RNA extraction and preparation of cDNA. qPCR was used to enumerate viable P. aeruginosa as well as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Burkholderia cepacia complex and Aspergillus fumigatus.ResultsFifteen CF patients were followed through 21 PEs. A complete set of serial sputum samples was unavailable for two patients (three separate PEs). P. aeruginosa numbers did not increase immediately prior to a PE, but numbers during intravenous antibiotic treatment were reduced ≥ 4-log in 6/18 and ≥ 1-log in 4/18 PEs. In 7/18 PEs, P. aeruginosa numbers changed very little with intravenous antibiotics and one patient demonstrated a ≥ 2-log increase in P. aeruginosa load. H. influenzae and S. pneumoniae were detected in ten and five PEs respectively, but with antibiotic treatment these bacteria rapidly became undetectable in 6/10 and 4/5 PEs, respectively. There was a negative correlation between P. aeruginosa numbers and FEV₁ during stable phase (r_s = 0.75, p < 0.05), and reductions in P. aeruginosa load with intravenous antibiotic treatment correlated with improved FEV₁ (r_s = 0.52, p < 0.05).ConclusionsExacerbations are not due to increased P. aeruginosa numbers in CF adults. However, lung function improvements correlate with reduced P. aeruginosa burden suggesting that current antibiotic treatment strategies remain appropriate in most patients. Improved understanding of PE characterised by unchanged P. aeruginosa numbers and minimal lung function improvement following treatment may allow better targeted therapies.     

The evaluation of nasal mupirocin to prevent Staphylococcus aureus burn wound colonization in routine clinical practice

BackgroundStaphylococcus aureus wound colonization frequently occurs in patients with burns and can cause impaired wound healing. Nasal mupirocin application may contribute to the reduction of burn wound colonization of endogenous origin, whereas colonization by the exogenous route can be reduced by blocking cross-infection from other sources. In this study we evaluated whether the implementation of routine treatment of patients and burn center personnel using nasal mupirocin ointment reduces S. aureus burn wound colonization.MethodsWe composed three study groups, consisting of a control period (Control), a mupirocin period (MUP), in which patients with burns were all receiving nasal mupirocin at admission, and a mupirocin + personnel period (MUP + P), in which we also screened the burn center personnel and decolonized S. aureus carriers by nasal mupirocin.ResultsThe patients who carried S. aureus in their nose and did not have S. aureus burn wound colonization at admission were considered as patients susceptible for the use of nasal mupirocin. In these patients, the S. aureus burn wound colonization rate was the same in all study groups. S. aureus nasal carriage was a significant independent risk factor for burn wound colonization (OR: 3.3; 95% CI: 1.4–7.6) when analyzed within the three study groups.ConclusionAlthough S. aureus carriage is a significant risk factor for developing burn wound colonization, the routine use of nasal mupirocin did not contribute to a reduction of burn wound colonization.     

Chronic Stenotrophomonas maltophilia infection and exacerbation outcomes in cystic fibrosis

BackgroundChronic Stenotrophomonas maltophilia infection is a risk factor for pulmonary exacerbation in cystic fibrosis (CF) but its impact on subsequent clinical outcomes is unknown. The aim of this study was to determine the effect of chronic S. maltophilia infection and associated antimicrobial therapy on the recovery of forced expiratory lung volume in 1 s (FEV₁) following pulmonary exacerbation.MethodsThis was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children and St. Michael's Hospital from 1997 to 2008. The primary outcome was the difference in FEV₁ percent predicted from baseline to follow up after a pulmonary exacerbation. Secondary outcomes for the effect of antimicrobial therapy included time to subsequent exacerbation.ResultsThere were 1667 pulmonary exacerbations in 440 CF patients. Patients with chronic S. maltophilia infection did not recover their baseline FEV₁ following 31% of exacerbations and had an overall mean FEV₁ decline of 1.84% predicted after exacerbation. Older (p = 0.02), female (p = 0.02) patients with lower BMI z score (p = 0.002) and Burkholderia cepacia complex infection (p = 0.005), but not chronic S. maltophilia infection (p = 0.86), had a greater decrease in follow up FEV₁% pred compared to baseline. The number of days of antibiotic therapy against S. maltophilia during a pulmonary exacerbation was not associated with a significant difference in the FEV₁ recovery (p = 0.69) or with a longer time to subsequent pulmonary exacerbation (p = 0.56).ConclusionsAlthough CF patients experience a significant decline in lung function following exacerbation, chronic S. maltophilia infection and associated antimicrobial therapy do not affect subsequent lung function recovery.     

Soluble squalamine tablets for the rapid disinfection of home nebulizers of cystic fibrosis patients

BackgroundThe bacterial contamination of nebulizers represents a major problem for cystic fibrosis (CF) patients that can lead to reduced nebulizer performance and increase the risk of patient reinfection by the contaminating bacteria.ObjectiveWe investigated the potential use of squalamine, a broad-spectrum antimicrobial compound, as a nebulizer disinfectant.MethodsPari LC nebulizers were artificially contaminated with a suspension of bacteria (Staphylococcus aureus and Pseudomonas aeruginosa; 10⁸ CFU/mL) and fungi (Candidida albicans and Aspergilus niger; 10⁷ CFU/mL) and then disinfected by immersion in squalamine solution for 20 min. Glutaraldehyde and Korsolex peracetic acid were used as disinfectant controls.ResultWe found that 0.5 g/L squalamine reduced the levels of viable S. aureus and P. aeruginosa by 5 log₁₀ and the level of viable C. albicans by 4 log₁₀ after 20 min. A concentration of 2 g/L was needed to reduce the level of A. niger cells by 4 log₁₀ in 6 hours. Finally, a formulation of squalamine in the form of a soluble disinfecting tablet containing 2.5% (w/w) squalamine was developed and successfully applied for nebulizer disinfection.ConclusionOur results suggest that aminosterol derivatives may be used by CF patients for rapid and easy home nebulizer disinfection and that soluble tablets may be developed for this purpose.     

Three-decade trends in the distribution of organisms causing septic arthritis in native joints: Single-center study of 374 cases

ObjectiveA rise in the incidence of septic arthritis due to methicillin-resistant Staphylococcus aureus (MRSA) has been reported in several parts of the world. Here, our objective was to look for changes over the last 30 years in the distribution and antibiotic susceptibility profiles of organisms responsible for septic arthritis.MethodsWe conducted a single-center retrospective study of all cases of septic arthritis documented by joint specimens and/or blood cultures between 1979 and 2008. Prosthetic joint infections were excluded.ResultsWe enrolled 374 patients, of whom 127, 136, and 111 were included during each decade, respectively. We detected no significant time trends in the proportions of staphylococci (67%, 65%, and 64%), streptococci (14%, 21%, and 17%), or Gram-negative rods (7%, 10%, and 14%). Tuberculosis was more common during the earliest decade (1979–1988, n = 10, 4, 2%; P < 0.05). No significant changes occurred in the proportions of methicillin-resistant staphylococci or MRSA (13%, 11%, 15%). Age and prevalence of risk factors for infection increased over time.ConclusionThe distribution and susceptibility of organisms causing septic arthritis has changed little over time. Our findings do not support the use of broader-spectrum antibiotics when empirical treatment is deemed necessary at our center.     

Prevalence and impact on FEV(1) decline of chronic methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with cystic fibrosis. A single-center, case control study of 165 patients

BackgroundRisk factors for methicillin-resistant Staphylococcus aureus (MRSA) in Cystic Fibrosis (CF) and the impact on CF disease progression are still under debate.The objectives of this study were to determine clinical variables associated with MRSA colonization and examine impact on FEV₁ evolution in CF patients.MethodsA retrospective case–control study using the University Hospital of Brussels CF clinic patient registry from 2002 to 2010, comparing clinical variables and decline of FEV₁ of MRSA positive patients with age and sex matched controls, chronically colonized with S. aureus.ResultsThirty of the 165 CF patients, chronically colonized with S. aureus, had cultures positive for MRSA (18.2%). Excluding patients under 4 years, the prevalence became 15.2% (23/151). Chronic colonization (i.e., three or more consecutive positive cultures) was found in 19/151 (12.6%).The MRSA positive group showed a higher proportion of patients with genotype F508del, less pancreas sufficient patients, more bronchiectasis and more frequent hospitalization.The FEV₁ recorded one year prior to, and at the moment of MRSA acquisition, was lower but not significantly different from that obtained in controls (72.9% ± 26.6 vs 84.3 ± 21.8 and 68.2% ± 27.1 vs 81.4% ± 24.3 respectively, p > 0.1). However, FEV₁ decline over 2- and 6-year periods, were significantly greater in the chronic MRSA group than in the controls (− 5% ± 5.5 vs −2.5 ± 2.3 over 2 years (p = 0.043) and − 1.8% ± 4.6 vs −1.0% ± 1.9 over a 6-year period (p = 0.026)).ConclusionIn our center the prevalence of MRSA in CF patients, chronically colonized with S. aureus and over the age of 4 years, was 15.2% (12.6% chronic infection). MRSA colonization was shown to be associated with a genotype F508del, presence of bronchiectasis and hospitalization. Our spirometric data also show that a MRSA episode entails an FEV₁ decline that is almost double that predicted for CF patients who can remain unaffected by MRSA.