A position statement on screening and management of prediabetes in adults in primary care in Australia.

Prediabetes has a high prevalence, with early detection essential to facilitate optimal management to prevent the development of conditions such as type 2 diabetes and cardiovascular disease. Prediabetes can include impaired fasting glucose, impaired glucose tolerance and elevated HbA1c. This position statement outlines the approaches to screening and management of prediabetes in primary care. There is good evidence to implement intensive, structured lifestyle interventions for individuals with impaired glucose tolerance. The evidence for those with impaired fasting glucose or elevated HbA1c is less clear, but individuals should still be provided with generalised healthy lifestyle strategies. A multidisciplinary approach is recommended to implement healthy lifestyle changes through education, nutrition and physical activity. Individuals should aim to lose weight (5-10% of body mass) using realistic and sustainable dietary approaches supported by an accredited practising dietitian, where possible. Physical activity and exercise should be used to facilitate weight maintenance and reduce blood glucose. Moderate-vigorous intensity aerobic exercise and resistance training should be prescribed by an accredited exercise physiologist, where possible. When indicated, pharmacotherapy, metabolic surgery and psychosocial care should be considered, in order to enhance the outcomes associated with lifestyle change. Individuals with prediabetes should generally be evaluated annually for their diabetes status.

Acute effects of viral respiratory tract infections on sputum bacterial density during CF pulmonary exacerbations.

BACKGROUND: Airway proliferation of Pseudomonas aeruginosa bacteria is thought to trigger CF exacerbations and may be affected by the presence of viral infections. METHODS: A 2-year prospective study was conducted on 35 adults with CF. P. aeruginosa sputum density was analyzed during stable, exacerbation and post exacerbation assessments. Upon exacerbation, samples were sent for PCR detection of respiratory viruses and the sputum density of P. aeruginosa in patients with a viral infection versus those without was compared. RESULTS: Twenty-two patients experienced 30 exacerbations during the study period; 50% were associated with a viral infection. There was no change in sputum density of P. aeruginosa from the stable to exacerbation state when measured by quantitative culture or by PCR. Virus-associated exacerbations did not result in significant increases in P. aeruginosa sputum density compared to non-viral exacerbations. CONCLUSION: Sputum density of P. aeruginosa was not increased at the time of CF exacerbation and was not influenced by the presence of viral infection.

Methylglyoxal: (active agent of manuka honey) in vitro activity against bacterial biofilms.

BACKGROUND: Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) biofilms are associated with poor chronic rhinosinusitis (CRS) disease control following surgery. Manuka honey (MH) has been shown to be both an effective in vitro treatment agent for SA and PA biofilms and nontoxic to sinonasal respiratory mucosa. Methylglyoxal (MGO) has been reported to be the major antibacterial agent in MH. The effect of this agent against SA and PA biofilms has yet to be reported. Our objective was to determine the in vitro effect of MGO against biofilms of SA and PA, via in vitro testing of MGO against bacterial biofilms. METHODS: An established biofilm model was used to determine the effective concentration (EC) of MGO against 10 isolates of methicillin-resistant SA (MRSA) and PA. The EC of MGO was also determined against planktonic (free-swimming) MRSA and PA. RESULTS: For MRSA, the EC against planktonic organisms was a concentration of 0.08 mg/mL to 0.3 mg/mL whereas against the biofilm MRSA isolates, the EC ranged from 0.5 mg/mL to 3.6 mg/mL. For PA, the EC against planktonic organisms was a concentration of 0.15 mg/mL to 1.2 mg/mL for planktonic organisms whereas against the biofilm PA isolates, the EC ranged from 1.8 mg/mL to 7.3 mg/mL. CONCLUSION: MGO, a component of MH, is an effective antimicrobial agent against both planktonic and biofilm MRSA and PA organisms in vitro.

Infection with transmissible strains of Pseudomonas aeruginosa and clinical outcomes in adults with cystic fibrosis.

CONTEXT: Studies from Australia and the United Kingdom have shown that some patients with cystic fibrosis are infected with common transmissible strains of Pseudomonas aeruginosa. OBJECTIVES: To determine the prevalence and incidence of infection with transmissible strains of P. aeruginosa and whether presence of the organism was associated with adverse clinical outcomes in Canada. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adult patients cared for at cystic fibrosis clinics in Ontario, Canada, with enrollment from September 2005 to September 2008. Sputum was collected at baseline, 3 months, and yearly thereafter for 3 years; and retrieved P. aeruginosa isolates were genotyped. Vital status (death or lung transplant) was assessed for all enrolled patients until December 31, 2009. MAIN OUTCOME MEASURES: Incidence and prevalence of P. aeruginosa isolation, rates of decline in lung function, and time to death or lung transplantation. RESULTS: Of the 446 patients with cystic fibrosis studied, 102 were discovered to be infected with 1 of 2 common transmissible strains of P. aeruginosa at study entry. Sixty-seven patients were infected with strain A (15%), 32 were infected with strain B (7%), and 3 were simultaneously infected with both strains (0.6%). Strain A was found to be genetically identical to the Liverpool epidemic strain but strain B has not been previously described as an epidemic strain. The incidence rate of new infections with these 2 transmissible strains was relatively low (7.0 per 1000 person-years; 95% confidence interval [CI], 1.8-12.2 per 1000 person-years). Compared with patients infected with unique strains of P. aeruginosa, patients infected with the Liverpool epidemic strain (strain A) and strain B had similar declines in lung function (difference in decline in percent predicted forced expiratory volume in the first second of expiration of 0.64% per year [95% CI, -1.52% to 2.80% per year] and 1.66% per year [95% CI, -1.00% to 4.30%], respectively). However, the 3-year rate of death or lung transplantation was greater in those infected with the Liverpool epidemic strain (18.6%) compared with those infected with unique strains (8.7%) (adjusted hazard ratio, 3.26 [95% CI, 1.41 to 7.54]; P = .01). CONCLUSIONS: A common strain of P. aeruginosa (Liverpool epidemic strain/strain A) infects patients with cystic fibrosis in Canada and the United Kingdom. Infection with this strain in adult Canadian patients with cystic fibrosis was associated with a greater risk of death or lung transplantation.

Effectiveness of honey on Staphylococcus aureus and Pseudomonas aeruginosa biofilms.

OBJECTIVES: Biofilms formed by Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) have been shown to be an important factor in the pathophysiology of chronic rhinosinusitis (CRS). As well, honey has been used as an effective topical antimicrobial agent for years. Our objective is to determine the in vitro effect of honey against biofilms produced by PA and SA. STUDY DESIGN: In vitro testing of honey against bacterial biofilms. METHODS: We used a previously established biofilm model to assess antibacterial activity of honey against 11 methicillin-susceptible SA (MSSA), 11 methicillin-resistant SA (MRSA), and 11 PA isolates. Honeys were tested against both planktonic and biofilm-grown bacteria. RESULTS: Honey was effective in killing 100 percent of the isolates in the planktonic form. The bactericidal rates for the Sidr and Manuka honeys against MSSA, MRSA, and PA biofilms were 63-82 percent, 73-63 percent, and 91-91 percent, respectively. These rates were significantly higher (P<0.001) than those seen with single antibiotics commonly used against SA. CONCLUSION: Honey, which is a natural, nontoxic, and inexpensive product, is effective in killing SA and PA bacterial biofilms. This intriguing observation may have important clinical implications and could lead to a new approach for treating refractory CRS.

Epidemiological investigation and glycotyping of clinical Pseudomonas aeruginosa isolates from patients with cystic fibrosis by mass spectrometry: association with multiple drug resistance.

The aim of the present investigation was to develop a novel approach for rapid identification and differentiation of Pseudomonas aeruginosa clones from Canadian cystic fibrosis patients by capillary electrophoresis-mass spectrometry. We screened P. aeruginosa isolates for lipopolysaccharide structure and presence/absence of alginate and correlated these findings with antibiotic resistance patterns.

A retrospective analysis of biofilm antibiotic susceptibility testing: a better predictor of clinical response in cystic fibrosis exacerbations.

BACKGROUND: Bacteria grow as biofilms within CF airways. However, antibiotic susceptibility testing is routinely performed on planktonically-growing bacteria. This study assessed whether CF patients infected with multiresistant organisms had improved clinical outcomes if given antibiotics that inhibited their biofilm-grown bacteria. METHODS: 110 patients with pulmonary exacerbations were treated with intravenous antibiotics based on susceptibility testing of planktonically-growing bacteria. A retrospective analysis was done using bacterial isolates grown from their sputum at exacerbation. Each isolate was grown as a biofilm and combination antibiotic susceptibility testing was performed. Clinical outcomes in patients treated with biofilm-susceptible antibiotics were compared to those that were not. RESULTS: 66 of 110 patients (60%) were treated with antibiotic combinations that inhibited all of their planktonically-grown bacterial isolates, however, when the same isolates were grown as biofilms, only 24 patients (22%) had all of their biofilm-grown isolates remaining susceptible to the antibiotics (P=<0.001 ). When patients with at least one biofilm-grown susceptible isolate (n=61) were compared to those with none (n=49), there was a significant decrease in sputum bacterial density (P=0.02) and length of stay (P=0.04) and a non-significant decrease in treatment failure. Survival analyses of time to next exacerbation showed non-significant trends favoring patients treated with biofilm-effective antibiotics. CONCLUSIONS: Most patients with CF exacerbations do not receive antibiotics that inhibit all biofilm-grown bacteria from their sputum at exacerbation. Patients treated with biofilm-effective therapy seemed to have improved clinical outcomes.

Infection with Burkholderia cepacia complex bacteria and pulmonary exacerbations of cystic fibrosis.

BACKGROUND: Studies have shown that cystic fibrosis (CF) patients who are chronically infected with Burkholderia cepacia complex bacteria may potentially acquire new strains of B cepacia. Our objective was to determine whether pulmonary exacerbations of CF are associated with acquisition of new B cepacia strains or with B cepacia strain replacement. METHODS: Thirty-six patients from seven centers who were chronically infected with B cepacia complex bacteria were prospectively followed up over a 38-month period. Patients had sputum cultures performed every 3 months while clinically stable and at the time of a pulmonary exacerbation. Each B cepacia complex isolate was speciated by polymerase chain reaction amplification of the recA gene to determine species status and was genotyped by pulsed-field gel electrophoresis to determine strain type. RESULTS: Thirty-five of 36 patients (97%) had chronic infection with Burkholderia cenocepacia III-A during clinical stability. All 36 patients maintained the same species and strain of B cepacia complex at the time of exacerbation as was found during clinical stability. B cepacia complex isolates retrieved during exacerbations were significantly less susceptible to ciprofloxacin, chloramphenicol, piperacillin, meropenem, and tobramycin compared to isolates retrieved from the same patients during clinical stability. CONCLUSION: Adult CF patients infected with B cenocepacia maintain the same strain of B cenocepacia during exacerbations; pulmonary exacerbations are not caused by acquisition of a new B cepacia species or strain. B cepacia isolates retrieved during exacerbations may be more resistant to antibiotics.

Multiple combination antibiotic susceptibility testing of nontypeable Haemophilus influenzae biofilms.

Haemophilus influenzae is a cause of otitis media with effusion (OME). Animal models demonstrate growth of H. influenzae biofilms in OME, which may explain why OME does not respond well to conventional antibiotic therapy. Using a previously developed in vitro model, we performed H. influenzae susceptibility studies to see if H. influenzae biofilm cultures were more resistant to antibiotics than planktonic (broth) cultures, and to determine which antibiotics were most effective against H. influenzae biofilms. H. influenzae isolates were grown as biofilms on polystyrene pins. Biofilm and planktonic minimum inhibitory concentrations (MICs) were measured for 8 antibiotics, and multiple combination testing was performed with 66 groupings of 1, 2, or 3 antibiotics. We found that biofilm cultures were more resistant to antibiotics than planktonic ones. Antibiotic combinations containing rifampin and ciprofloxacin were most effective against biofilms. Biofilm testing reveals differences in effectiveness among antibiotics not apparent from conventional susceptibility testing, and suggests novel antibiotic regimens that could be studied for treatment of OME.

Multiple combination bactericidal testing of staphylococcal biofilms from implant-associated infections.

Standardized susceptibility testing fails to predict in vivo resistance of device-related infections to antimicrobials. We assessed agents and combinations of antimicrobials against clinical isolates of Staphylococcus epidermidis and S. aureus (methicillin-resistant S. aureus and methicillin-sensitive S. aureus) retrieved from device-associated infections. Isolates were grown planktonically and as biofilms. Biofilm cultures of the organisms were found to be much more resistant to inhibitory and bactericidal effects of single and combination antibiotics than planktonic cultures (P < 0.001). Rifampin was the most common constituent of antibiotic combinations active against staphylococcal biofilms. Other frequently effective antimicrobials were vancomycin and fusidic acid. Susceptibility testing involving biofilm-associated bacteria suggests new options for combination antibiotic therapy.

Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial.

BACKGROUND: We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. METHODS: 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870. FINDINGS: 132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups. INTERPRETATION: Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.

Adult cystic fibrosis exacerbations and new strains of Pseudomonas aeruginosa.

We hypothesized that in adults with cystic fibrosis, the acquisition of a new strain of Pseudomonas aeruginosa may be associated with a pulmonary exacerbation. Eighty-four patients who were chronically infected with P. aeruginosa were prospectively followed from eight centers over a 26-month period. Patients had sputum cultures performed every 3 months while clinically stable and at the time of an exacerbation. Forty patients (48%) had an exacerbation requiring intravenous antibiotics during the study period, and in 36 of these patients, their P. aeruginosa isolates were genetically typeable by pulsed-field gel electrophoresis. In 34 of the 36 patients (94%), P. aeruginosa recovered during clinical stability and at exacerbation were of the same genotype. In only two patients (6%; 95% confidence interval, 0-18%) was a new P. aeruginosa clone cultured during an exacerbation that had not been cultured during clinical stability. There were no significant differences in antibiotic susceptibilities, measured as mean minimal inhibitory concentrations, for isolates retrieved during clinically stable periods compared with isolates retrieved during exacerbations. We conclude that for the majority of adult patients with cystic fibrosis a new pulmonary exacerbation is not caused by the acquisition of a new strain of P. aeruginosa.

Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine.

Serum bactericidal activity confers protection against meningococcal disease, but it is not known whether vaccine-induced anticapsular antibodies that lack bactericidal activity are protective. We developed an infant rat challenge model using a naturally occurring O-acetylated strain of Neisseria meningitidis group C and a strain that was negative for O acetylation (OAc). Rats 4 to 7 days of age inoculated intraperitoneally (i.p.) with approximately 10(3) CFU of either strain developed >5 x 10(5) CFU/ml of blood obtained 18 h later. Dilutions of preimmunization sera given i.p. 2 h before the bacterial challenge had no effect on bacteremia, whereas group C anticapsular antibody in sera from adults immunized with meningococcal polysaccharide vaccine conferred complete or partial (>99% decrease in CFU per milliliter of blood) protection against the OAc-positive or OAc-negative strain, respectively, at antibody doses as low as 0.04 micro g/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 micro g/rat) in pooled sera from children immunized at a mean age of 2.6 years failed to protect rats, but antibody at the same or fivefold-lower dose in a serum pool from a group of children immunized at 4 years of age gave complete or partial protection. Protective activity was observed with some serum pools that lacked detectable complement-mediated bactericidal activity (titers < 1:4) and correlated with increasing antibody avidity. Thus, not only does the magnitude of the group C antibody response to meningococcal polysaccharide vaccine increase with increasing age but there are also age-related affects on antibody functional activity such that higher serum concentrations of vaccine-induced antibody are required for protection of immunized children than for immunized adults.

Single and combination antibiotic susceptibilities of planktonic, adherent, and biofilm-grown Pseudomonas aeruginosa isolates cultured from sputa of adults with cystic fibrosis.

Evidence suggests that Pseudomonas aeruginosa bacteria form biofilms within the airways of adults with cystic fibrosis (CF). The objective of this study was to determine whether clinical isolates of P. aeruginosa recovered from adults with CF have similar susceptibilities to individual antibiotics and to antibiotic combinations when grown as adherent monolayers or as biofilms compared to when they are grown using planktonic methods. Twelve multiresistant P. aeruginosa isolates, one mucoid and one nonmucoid from each of six CF patients, were grown conventionally under planktonic conditions, as adherent bacterial monolayers, and as biofilms. Each bacterial isolate remained genotypically identical despite being cultured under planktonic, adherent, or biofilm growth conditions. Isolates grown as adherent monolayers and as biofilms were less susceptible to bactericidal killing by individual antibiotics compared to those grown planktonically. More importantly, biofilm-grown bacteria, but not adherent monolayer-grown bacteria, were significantly less susceptible to two- and three-drug combinations of antibiotics than were planktonically grown bacteria (P = 0.005). We conclude that biofilm-grown bacteria derived from patients with CF show decreased susceptibility to the bactericidal effects of antibiotic combinations than do adherent and planktonically grown bacteria.