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Xanthomonas maltophilia [keywords]
- A Linkage between SmeIJK Efflux Pump, Cell Envelope Integrity, and σE-Mediated Envelope Stress Response in Stenotrophomonas maltophilia. [Journal Article]
- PLoS One 2014; 9(11):e111784.
Resistance nodulation division (RND) efflux pumps, such as the SmeIJK pump of Stenotrophomonas maltophilia, are known to contribute to the multidrug resistance in Gram-negative bacteria. However, some RND pumps are constitutively expressed even though no antimicrobial stresses occur, implying that there should be some physical implications for these RND pumps. In this study, the role of SmeIJK in antimicrobials resistance, envelope integrity, and σE-mediated envelope stress response (ESR) of S. maltophilia was assessed. SmeIJK was involved in the intrinsic resistance of S. maltophilia KJ to aminoglycosides and leucomycin. Compared with the wild-type KJ, the smeIJK deletion mutant exhibited growth retardation in the MH medium, an increased sensitivity to membrane-damaging agents (MDAs), as well as activation of an σE-mediated ESR. Moreover, the expression of smeIJK was further induced by sub-lethal concentrations of MDAs or surfactants in an σE-dependent manner. These data collectively suggested an alternative physiological role of smeIJK in cell envelope integrity maintenance and σE-mediated ESR beyond the efflux of antibiotics. Because of the necessity of the physiological role of SmeIJK in protecting S. maltophilia from the envelope stress, smeIJK is constitutively expressed, which, in turn, contributes the intrinsic resistance to aminoglycoside and leucomycin. This is the first demonstration of the linkage among RND-type efflux pump, cell envelope integrity, and σE-mediated ESR in S. maltophilia.
- Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2014 Nov 10.:CD004197.
Respiratory tract infection with Pseudomonas aeruginosa occurs in most people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.This is an update of a Cochrane review first published in 2003, and previously updated in 2006 and 2009.To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement. To evaluate whether there is evidence that a particular antibiotic strategy is superior to or more cost-effective than other strategies and to compare the adverse effects of different antibiotic strategies (including respiratory infection with other micro-organisms).We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 08 September 2014.We included randomised controlled trials of people with cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls.Both authors independently selected trials, assessed risk of bias and extracted data.The search identified 49 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low numbers of participants and most had relatively short follow-up periods; however, there was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment given the interventions and comparators used. Two trials were supported by the manufacturers of the antibiotic used.Evidence from two trials (38 participants) at the two-month time-point showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence interval 0.03 to 0.65) and data from one of these trials, with longer follow up, suggested that this effect may persist for up to 12 months.One randomised controlled trial (26 participants) compared oral ciprofloxacin and nebulised colistin versus usual treatment. Results after two years suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% confidence interval 0.02 to 0.79).One trial comparing 28 days to 56 days treatment with nebulised tobramycin solution for inhalation in 88 participants showed that both treatments were effective and well-tolerated, with no notable additional improvement with longer over shorter duration of therapy. However, this trial was not powered to detect non-inferiority or equivalence .A trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for inhalation alone (223 participants) failed to show a difference between the two strategies, although it was underpowered to show this. A further trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin solution for inhalation with oral ciprofloxacin also showed no superiority of the former, with increased isolation of Stenotrophomonas maltophilia in both groups.A recent, large trial in 306 children aged between one and 12 years compared cycled nebulised tobramycin solution for inhalation to culture-based therapy and also ciprofloxacin to placebo. The primary analysis showed no difference in time to pulmonary exacerbation or proportion of Pseudomonas aeruginosa positive cultures. An analysis performed in this review (not adjusted for age) showed fewer participants in the cycled therapy group with one or more isolates of Pseudomonas aeruginosa, odds ratio 0.51 (95% CI 0.31 to 0.28).We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained for up to two years. There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials of two active treatments have failed to show differences in rates of eradication of Pseudomonas aeruginosa. There have been no published randomised controlled trials that investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in cystic fibrosis.
- Exploring nicotinamide cofactor promiscuity in NAD(P)H-dependent flavin containing monooxygenases (FMOs) using natural variation within the phosphate binding loop. Structure and activity of FMOs from Cellvibrio sp. BR and Pseudomonas stutzeri NF13. [JOURNAL ARTICLE]
- J Mol Catal B Enzym 2014 Nov.:191-198.
Flavin-containing monooxygenases (FMOs) catalyse asymmetric oxidation reactions that have potential for preparative organic synthesis, but most use the more expensive, phosphorylated nicotinamide cofactor NADPH to reduce FAD to FADH2 prior to formation of the (hydro)peroxy intermediate required for substrate oxygenation. A comparison of the structures of NADPH-dependent FMO from Methylophaga aminisulfidivorans (mFMO) and SMFMO from Stenotrophomonas maltophilia, which is able to use both NADPH and NADH, suggested that the promiscuity of the latter enzyme may be due in part to the substitution of an Arg-Thr couple in the NADPH phosphate recognition site in mFMO, for a Gln-His couple in SMFMO (Jensen et al., 2012, Chembiochem, 13, 872-878). Natural variation within the phosphate binding region, and its influence on nicotinamide cofactor promiscuity, was explored through the cloning, expression, characterisation and structural studies of FMOs from Cellvibrio sp. BR (CFMO) and Pseudomonas stutzeri NF13 (PSFMO), which possess Thr-Ser and Gln-Glu in the putative phosphate recognition positions, respectively. CFMO and PSFMO displayed 5- and 1.5-fold greater activity, respectively, than SMFMO for the reduction of FAD with NADH, and were also cofactor promiscuous, displaying a ratio of activity with NADH:NADPH of 1.7:1 and 1:1.3, respectively. The structures of CFMO and PSFMO revealed the context of the phosphate binding loop in each case, and also clarified the structure of the mobile helix-loop-helix motif that appears to shield the FAD-binding pocket from bulk solvent in this class of FMOs, a feature that was absent from the structure of SMFMO.
- Bacterial constituents of indoor air in a high throughput building in the tropics. [Journal Article]
- Trop Biomed 2014 Sep; 31(3):540-56.
Airborne bacteria are significant biotic constituents of bioaerosol. Bacteria at high concentrations in the air can compromise indoor air quality (IAQ) and result in many diseases. In tropical environments like Malaysia that extensively utilize air-conditioning systems, this is particularly significant due to continuous recirculation of indoor air and the potential implications for human health. Currently, there is a lack of knowledge regarding the impact of airborne bacteria on IAQ in Malaysia. This study was prompted by a need for reliable baseline data on airborne bacteria in the indoor environment of tropical equatorial Malaysia, that may be used as a reference for further investigations on the potential role played by airborne bacteria as an agent of disease in this region. It was further necessitated due to the threat of bioterrorism with the potentiality of release of exotic pathogenic microorganisms into indoor or outdoor air. Before scientists can detect the latter, a gauge of the common microorganisms in indoor (as well as outdoor) air needs to be ascertained, hence the expediency of this study. Bacterial counts from the broad-based and targeted study were generally in the order of 10² colony-forming units (CFU) per m³ of air. The most prevalent airborne bacteria found in the broad-based study that encompassed all five levels of the building were Gram-positive cocci (67.73%), followed by Gram-positive rods (24.26%) and Gram-negative rods (7.10%). Gram-negative cocci were rarely detected (0.71%). Amongst the genera identified, Kytococcus sp., Micrococcus sp., Staphylococcus sp., Leifsonia sp., Bacillus sp. and Corynebacterium sp. predominated in indoor air. The most dominant bacterial species were Kytococcus sedentarius, Staphylococcus epidermidis and Micrococcus luteus. The opportunistic and nosocomial pathogen, Stenotrophomonas maltophilia was also discovered at a high percentage in the cafeteria. The bacteria isolated in this study have been increasingly documented to cause opportunistic infections in immuno-compromised patients, sometimes with fatal outcomes. Furthermore, some of them are becoming increasingly resistant to antibiotics. Hence, we propose that indoor reservoirs of these bacteria and their associated clinical and more subtle health effects, if any, be investigated further.
- Blood infections in patients treated at transplantation wards of a clinical hospital in warsaw. [Journal Article]
- Transplant Proc 2014; 46(8):2589-91.
Establishment of the etiology in blood infection is always advisable. The purpose of this study was to evaluate the proportion of different bacterial species, including aerobic and anaerobic bacteria in blood cultures of patients hospitalized in transplantation wards of a large clinical hospital between 2010 and 2012. A total of 1994 blood samples from patients who were treated at one of two transplantation wards of a large hospital in Warsaw were analyzed using an automated blood culture system, BacT/ALERT (bioMerieux, France). The 306 bacterial strains were obtained from the examined samples. The highest proportion were bacteria from the family Enterobacteriaceae (112 strains; 36.6%) with Escherichia coli (61 strains), Klebsiella pneumoniae (30 strains), and Enterobacter cloacae (10 strains) most commonly isolated. The non-fermenting bacilli constituted 21.6% (66 strains), with most common Stenotrophomonas maltophilia (31 strains), Pseudomonas aeruginosa (14 strains), Achromobacter spp. (12 strains), and Acinetobacter baumannii (3 strains). Most frequent Gram-positive bacteria were staphylococci (25.2%). Of 77 staphylococcal strains, 56 were coagulase-negative staphylococci and 21 Staphylococcus aureus. Other Gram-positive bacteria included enterococci (14 strains) and Streptococcus pneumoniae (1 strain). Obligatory anaerobic bacteria were represented by 19 strains (6.2% of total isolates). Among all Enterobacteriaceae, 49 isolates (43.7%) produced extended-spectrum β-lactamases (ESBLs). Resistance to methicillin was detected in 62% of S aureus isolates and in 46% of coagulase-negative staphylococci. Of 14 enterococci cultured from blood samples, 2 strains (14.3%) were resistant to vancomycin. Both were Enterococcus faecium. Resistant strains of Gram-negative and Gram-positive bacteria are significant problems for patients in the transplantation ward.
- Risk Factors and Outcomes of Stenotrophomonas maltophilia Bacteraemia: A Comparison with Bacteraemia Caused by Pseudomonas aeruginosa and Acinetobacter Species. [Journal Article]
- PLoS One 2014; 9(11):e112208.
Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen that exhibits intrinsic resistance to various antimicrobial agents. However, the risk factors for SM bacteraemia have not been sufficiently evaluated. From January 2005 to September 2012, we retrospectively compared the clinical backgrounds and outcomes of SM bacteraemic patients (SM group) with those of bacteraemic patients due to Pseudomonas aeruginosa (PA group) or Acinetobacter species (AC group). DNA genotyping of the SM isolates using the Diversilab system was performed to investigate the genetic relationships among the isolates. The SM, PA, and AC groups included 54, 167, and 69 patients, respectively. Nine of 17 patients in the SM group receiving trimethoprim-sulfamethoxazole prophylaxis developed SM bacteraemia. Independent risk factors for SM bacteraemia were the use of carbapenems and antipseudomonal cephalosporins and SM isolation within 30 days prior to the onset of bacteraemia. Earlier SM isolation was observed in 32 of 48 patients (66.7%) with SM bacteraemia who underwent clinical microbiological examinations. Of these 32 patients, 15 patients (46.9%) had the same focus of bacteraemia as was found in the previous isolation site. The 30-day all-cause mortality rate among the SM group (33.3%) was higher than that of the PA group (21.5%, p = 0.080) and the AC group (17.3%, p = 0.041). The independent factor that was associated with 30-day mortality was the SOFA score. DNA genotyping of SM isolates and epidemiological data suggested that no outbreak had occurred. SM bacteraemia was associated with high mortality and should be considered in patients with recent use of broad-spectrum antibiotics or in patients with recent isolation of the organism.
- Update on acinetobacter species: mechanisms of antimicrobial resistance and contemporary in vitro activity of minocycline and other treatment options. [Journal Article]
- Clin Infect Dis 2014 Dec 1.:S367-73.
Among Acinetobacter species, A. baumannii and other closely related species are commonly implicated in nosocomial infections. These organisms are usually multidrug resistant (MDR), and therapeutic options to treat A. baumannii infections are very limited. Clinicians have been resorting to older antimicrobial agents to treat infections caused by MDR A. baumannii, and some of these agents have documented toxicity and/or are not optimized for the infection type to be treated. Recent clinical experience supported by antimicrobial susceptibility data suggests that minocycline has greater activity than other tetracyclines and glycylcyclines against various MDR pathogens that have limited therapeutic options available, including Acinetobacter species. An intravenous formulation of minocycline has recently become available for clinical use, and in contrast to most older tetracyclines, minocycline has high activity against Acinetobacter species. In this report, we summarized some of the characteristics of the tetracycline class, and quantified the minocycline activity against contemporary (2007-2011) isolates and its potential therapeutic role against a collection of 5477 A. baumannii and other relevant gram-negative organisms when compared directly with tetracycline, doxycycline, and other broad-spectrum antimicrobial agents. Acinetobacter baumannii strains were highly resistant to all agents tested, with the exception of minocycline (79.1% susceptible) and colistin (98.8% susceptible). Minocycline (minimum inhibitory concentration that inhibits 50% and 90% of the isolates [MIC50/90]: 1/8 µg/mL) displayed greater activity than doxycycline (MIC50/90: 2/>8 µg/mL) and tetracycline hydrochloride (HCL) (only 30.2% susceptible) against A. baumannii isolates, and was significantly more active than other tetracyclines against Burkholderia cepacia, Escherichia coli, Serratia marcescens, and Stenotrophomonas maltophilia isolates. In vitro susceptibility testing using tetracycline HCL as a surrogate for the susceptibility other tetracyclines fails to detect minocycline-susceptible isolates and the potential utility of minocycline for the treatment of many MDR A. baumannii infections and other difficult-to-treat species, where there are often limited choices of antimicrobials.
- Rapid identification of Stenotrophomonas maltophilia by peptide nucleic acid fluorescence in situ hybridization. [Journal Article]
- New Microbes New Infect 2014 May; 2(3):79-81.
The objective of this study was to develop a novel peptide nucleic acid (PNA) probe for Stenotrophomonas maltophilia identification by fluorescence in situ hybridization (FISH). The probe was evaluated using 33 human and veterinary clinical S. maltophilia isolates and 45 reference strains representing common bacterial species in the respiratory tract. The probe displayed 100% sensitivity and 100% specificity on pure cultures and allowed detection in sputum from cystic fibrosis patients. The detection limit was 10(4) CFU/mL in spiked tracheal aspirate and bronchoalveolar lavage from healthy horses. Altogether the study shows that this species-specific PNA FISH probe facilitates rapid detection of S. maltophilia in biological specimens.
- Antibiotic-resistant gram-negative bacterial infections in patients with cancer. [Journal Article]
- Clin Infect Dis 2014 Nov 15.:S335-9.
Patients with cancer are at high risk for infections caused by antibiotic resistant gram-negative bacteria. In this review, we summarize trends among the major pathogens and clinical syndromes associated with antibiotic resistant gram-negative bacterial infection in patients with malignancy, with special attention to carbapenem and expanded-spectrum β-lactam resistance in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia-all major threats to our cancer patients. Optimal therapy for these antibiotic-resistant pathogens still remains to be determined.
- [A retrospective clinicopathological study of aspiration pneumonia in the elderly]. [English Abstract, Journal Article]
- Zhonghua Jie He He Hu Xi Za Zhi 2014 Aug; 37(8):592-6.
To explore the clinicopathological characteristics of aspiration pneumonia in the elderly.The clinical data of 30 cases of autopsy-proven aspiration pneumonia in Beijing Hospital from 1973 to 2002 were reviewed. The patients consisted of 28 males and 2 females, aged from 63 to 103 [mean (83 ± 9)] years.Only 15 cases were clinically diagnosed as aspiration pneumonia before death. Concomitant diseases were severe and complex, mostly coronary disease, cerebrovascular disease, hypertension, COPD, and diabetes mellitus. All the patients suffered from at least 3 concomitant diseases. Long-term bedridden and nasogastric feeding was seen in 11 and 17 patients respectively. The clinical presentation and chest X-ray of aspiration pneumonia in the elderly were nonspecific and variable. Mixed infections were common . The main bacteria isolated were Gram-negative bacilli, in particular Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli and Candida albicans. By pathology, macrophages with foreign bodies were found in all the 30 cases and multiple small abscesses were found in 14 cases. The lesions were adjacent to the bronchioles and in the lung tissue around the bronchioles, mostly multi-lobar and bilateral. Unilateral or bilateral pleural effusion developed in 20 patients. The accordance between radiological and pathological diagnosis of aspiration pneumonia was very poor. The foci of infection detected by X-ray were proven by autopsy in 13 patients, while pleural effusions in X-ray were proven by autopsy in 15 patients.Multi-concomitant diseases, mixed infection and extra-pulmonary presentations were common in elderly patients with aspiration pneumonia. Multiple small abscesses were the pathological characteristics of aspiration pneumonia in the aged. A definite clinical diagnosis of aspiration pneumonia was difficult. Recurrent silent microaspiration was a feature of aspiration in the elderly. The assessment of risk factor of aspiration played an important role in the clinical diagnosis of aspiration pneumonia.