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author:("cherny, Iris")
1.  Quantitative Contributions of Target Alteration and Decreased Drug Accumulation to Pseudomonas aeruginosa Fluoroquinolone Resistance 
Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence and spread of resistance increasingly limits the use of fluoroquinolones in the treatment and management of microbial disease. In this study, we evaluated the quantitative contributions of quinolone target alteration and efflux pump expression to fluoroquinolone resistance in Pseudomonas aeruginosa. We generated isogenic mutations in hot spots of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, and parC and inactivated the efflux regulator genes so as to overexpress the corresponding multidrug resistance (MDR) efflux pumps. We then introduced the respective mutations into the reference strain PA14 singly and in various combinations. Whereas the combined inactivation of two efflux regulator-encoding genes did not lead to resistance levels higher than those obtained by inactivation of only one efflux regulator-encoding gene, the combination of mutations leading to increased efflux and target alteration clearly exhibited an additive effect. This combination of target alteration and overexpression of efflux pumps was commonly observed in clinical P. aeruginosa isolates; however, these two mechanisms were frequently found not to be sufficient to explain the level of fluoroquinolone resistance. Our results suggest that there are additional mechanisms, independent of the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and/or MexXY-OprM efflux pump, that increase ciprofloxacin resistance in isolates with mutations in the QRDRs.
PMCID: PMC3591863  PMID: 23274661
2.  Individual units rather than entire hospital as the basis for improvement: the example of two Methicillin resistant Staphylococcus aureus cohort studies 
Two MRSA surveillance components exist within the German national nosocomial infection surveillance system KISS: one for the whole hospital (i.e. only hospital based data and no rates for individual units) and one for ICU-based data (rates for each individual ICU). The objective of this study was to analyze which surveillance system (a hospital based or a unit based) leads to a greater decrease in incidence density of nosocomial MRSA
Two cohort studies of surveillance data were used: Data from a total of 224 hospitals and 359 ICUs in the period from 2004 to 2009. Development over time was described first for both surveillance systems. In a second step only data were analyzed from those hospitals/ICUs with continuous participation for at least four years. Incidence rate ratios (IRR) with 95% confidence intervals were calculated to compare incidence densities between different time intervals.
In the baseline year the mean MRSA incidence density of hospital acquired MRSA cases was 0.25 and the mean incidence density of ICU-acquired MRSA was 1.25 per 1000 patient days. No decrease in hospital-acquired MRSA rates was found in a total of 111 hospitals with continuous participation in the hospital- based system. However, in 159 ICUs with continuous participation in the unit-based system, a significant decrease of 29% in ICU-acquired MRSA was identified.
A unit-based approach of surveillance and feedback seems to be more successful in decreasing nosocomial MRSA rates, compared to a hospital-based approach. Therefore each surveillance system should provide unit-based data to stimulate activities on the unit level.
PMCID: PMC3436609  PMID: 22958320
Infection prevention; Surveillance; MRSA; Quality management
3.  Five-years surveillance of invasive aspergillosis in a university hospital 
BMC Infectious Diseases  2011;11:163.
As the most common invasive fungal infection, invasive aspergillosis (IA) remains a serious complication in immunocompromised patients, leading to increased mortality. Antifungal therapy is expensive and may result in severe adverse effects.
The aim of this study was to determine the incidence of invasive aspergillosis (IA) cases in a tertiary care university hospital using a standardized surveillance method.
All inpatients at our facility were screened for presence of the following parameters: positive microbiological culture, pathologist's diagnosis and antifungal treatment as reported by the hospital pharmacy. Patients fulfilling one or more of these indicators were further reviewed and, if appropriate, classified according to international consensus criteria (EORTC).
704 patients were positive for at least one of the indicators mentioned above. Applying the EORTC criteria, 214 IA cases were detected, of which 56 were proven, 25 probable and 133 possible. 44 of the 81 (54%) proven and probable cases were considered health-care associated. 37 of the proven/probable IA cases had received solid organ transplantation, an additional 8 had undergone stem cell transplantation, and 10 patients were suffering from some type of malignancy. All the other patients in this group were also suffering from severe organic diseases, required long treatment and experienced several clinical complications. 7 of the 56 proven cases would have been missed without autopsy. After the antimycotic prophylaxis regimen was altered, we noticed a significant decrease (p = 0.0004) of IA during the investigation period (2003-2007).
Solid organ and stem cell transplantation remain important risk factors for IA, but several other types of immunosuppression should also be kept in mind. Clinical diagnosis of IA may be difficult (in this study 13% of all proven cases were diagnosed by autopsy only). Thus, we confirm the importance of IA surveillance in all high-risk patients.
PMCID: PMC3128051  PMID: 21651773
surveillance; invasive Aspergillosis; epidemiology; pathology
4.  The microbiological quality of air improves when using air conditioning systems in cars 
BMC Infectious Diseases  2010;10:146.
Because of better comfort, air conditioning systems are a common feature in automobiles these days. However, its impact on the number of particles and microorganisms inside the vehicle - and by this its impact on the risk of an allergic reaction - is yet unknown.
Over a time period of 30 months, the quality of air was investigated in three different types of cars (VW Passat, VW Polo FSI, Seat Alhambra) that were all equipped with a automatic air conditioning system. Operation modes using fresh air from outside the car as well as circulating air from inside the car were examined. The total number of microorganisms and the number of mold spores were measured by impaction in a high flow air sampler. Particles of 0.5 to 5.0 μm diameter were counted by a laser particle counter device.
Overall 32 occasions of sampling were performed. The concentration of microorganisms outside the cars was always higher than it was inside the cars. Few minutes after starting the air conditioning system the total number of microorganisms was reduced by 81.7%, the number of mold spores was reduced by 83.3%, and the number of particles was reduced by 87.8%. There were no significant differences neither between the types of cars nor between the types of operation mode of the air conditioning system (fresh air vs. circulating air). All parameters that were looked for in this study improved during utilization of the car's air conditioning system.
We believe that the risk of an allergic reaction will be reduced during use also. Nevertheless, we recommend regular maintenance of the system and replacement of older filters after defined changing intervals.
PMCID: PMC2890006  PMID: 20515449

Results 1-4 (4)