Wiesława Duszyńska

Therapeutic drug monitoring of amikacin in septic patients.

IntroductionUse of higher than standard doses of amikacin (AMK) has been proposed during sepsis, especially to treat less susceptible bacterial strains. However, few data are available on drug concentrations during prolonged therapy and on potential adverse events related to this strategy.MethodsSixty-three critically ill patients who required AMK administration for the treatment of severe infection were included in this study. After a loading dose (LD, 18 to 30 mg/kg), the daily regimen was adapted using therapeutic drug monitoring (TDM) of both peak (Cpeak) and trough (Cmin) concentrations. Target concentrations had to give a ratio of at least 8 between Cpeak and the minimal inhibitory concentration (MIC) of the isolated pathogen. A Cmin >5 mg/L was considered as potentially nephrotoxic. We recorded clinical and microbiological responses, the development of acute kidney injury (AKI) during therapy and ICU mortality.ResultsThe median AMK LD was 1500 (750 to 2400) mg, which resulted in a Cpeak/MIC ≥8 in 40 (63%) patients. Increasing the dose in the 23 patients with a Cpeak/MIC <8 resulted in optimal Cpeak/MIC in 15 of these patients (79%). In 23 patients (37%), Cmin was >5mg/L after the LD, notably in the presence of altered renal function at the onset of therapy, needing prolongation of drug administration. Overall, only 11 patients (17%) required no dose or interval adjustment during AMK therapy. Clinical cure (32/37 (86%) vs. 16/23 (70%), P = 0.18)) and microbiological eradication (29/35 (83%) vs. 14/23 (61%), P = 0.07) were higher in patients with an initial optimal Cpeak/MIC than in the other patients. The proportion of patients with clinical cure significantly improved as the Cpeak/MIC increased (P = 0.006). Also, increased time to optimal Cpeak was associated with worse microbiological and clinical results. AKI was identified in 15 patients (24%) during AMK therapy; 12 of these patients already had altered renal function before drug administration. Survivors (n = 47) had similar initial Cpeak/MIC ratios but lower Cmin values compared to nonsurvivors.ConclusionsTDM resulted in adjustment of AMK therapy in most of our septic patients. Early achievement of an optimal Cpeak/MIC ratio may have an impact on clinical and microbiological responses, but not on outcome. In patients with impaired renal function prior to treatment, AMK therapy may be associated with a further decline in renal function.

Device-associated infection rates and extra length of stay in an intensive care unit of a university hospital in Wroclaw, Poland: International Nosocomial Infection Control Consortium's (INICC) findings

PURPOSE The aim of this study was to determine device-associated health care-associated infections (DA-HAI) rates, microbiologic profile, bacterial resistance, and length of stay in one intensive care unit (ICU) of a hospital member of the International Nosocomial Infection Control Consortium (INICC) in Poland. MATERIALS AND METHODS A prospective DA-HAI surveillance study was conducted on an adult ICU from January 2007 to May 2010. Data were collected by implementing the methodology developed by INICC and applying the definitions of DA-HAI provided by the National Healthcare Safety Network at the US Centers for Disease Control and Prevention. RESULTS A total of 847 patients hospitalized for 9386 days acquired 206 DA-HAIs, an overall rate of 24.3% (95% confidence interval [CI], 21.5-27.4), and 21.9 (95% CI, 19.0-25.1) DA-HAIs per 1000 ICU-days. Central line-associated bloodstream infection rate was 4.01 (95% CI, 2.8-5.6) per 1000 catheter-days, ventilator-associated pneumonia rate was 18.2 (95% CI, 15.5-21.6) per 1000 ventilator-days, and catheter-associated urinary tract infection rate was 4.8 (95% CI, 3.5-6.5) per 1000 catheter-days. Length of stay was 6.9 days for those patients without DA-HAI, 10.0 days for those with central line-associated bloodstream infection, 15.5 days for those with ventilator-associated pneumonia, and 15.0 for those with catheter-associated urinary tract infection. CONCLUSIONS Most DA-HAI rates are lower in Poland than in INICC, but higher than in the National Healthcare Safety Network, expressing the feasibility of lowering infection rates and increasing patient safety.

Continuous infusion of piperacillin/tazobactam in ventilator-associated pneumonia: a pilot study on efficacy and costs

Ventilator-associated pneumonia (VAP) occurs in nearly one-third of mechanically ventilated patients in the Intensive Care Unit. Piperacillin/tazobactam (TZP) is currently recommended in the empirical treatment of VAP, but intermittent dosing may result in inadequate serum concentrations. The efficacy and costs of continuous infusion (CI) of TZP, using therapeutic drug monitoring for real-time dose adjustment, was assessed in a prospective pilot study of 16 patients with VAP. TZP was given as a loading dose of 2.0/0.25 g followed by a CI of 10.0/1.25g daily. Rapid antimicrobial susceptibility testing was used to determine the minimum inhibitory concentration (MIC) of the pathogens. TZP concentrations were determined by high-pressure liquid chromatography before and at 1, 6, 12, 24, 48, 72 and 96 h after the onset of administration. Dosages were adjusted to maintain piperacillin concentrations four-fold above the MIC (T>4 × MIC) of the pathogen, with a maximum dose of 16.0/2.0 g. The cost of the total TZP administered was compared with the cost of a standard TZP regimen (16.0/2.0 g) if given over the same period of time. The median MIC for TZP was 1 μg/mL (range 0.025-32 μg/mL). TZP concentrations were adequate for 71% of pathogens on the first day of therapy. Clinical cure was achieved in 9/10 patients who had adequate drug concentrations and in 3/6 patients with insufficient levels. The daily dose of TZP received by CI was 37.5% less than that of a standard regimen, which corresponds to a saving of €15 on daily therapy costs compared with the standard regimen. In conclusion, CI of TZP achieved optimal drug concentrations in most patients with VAP, with a favourable impact on costs. Adequate drug concentrations were achieved for MIC ≤ 4 μg/mL, but higher dosages should be considered for the treatment of pathogens with low susceptibility thresholds.

Ventilator-associated pneumonia monitoring according to the INICC project at one centre.

BACKGROUND Pneumonia is a common complication of hospitalisation in severely ill patients who need mechanical ventilation. The aim of this study was to assess the usefulness of the International Nosocomial Infection Control Consortium programme for the surveillance of ventilator-associated pneumonia (VAP). METHODS A prospective study (1 Jan 2012-30 June 2014) was conducted in the 20-bed ICU. The device utilisation ratios for lung ventilation and the frequency (density and incidence) and aetiology of VAP were estimated in ICU patients. RESULTS From a total of 1097 patients, VAP infections were diagnosed in 93. Thirty percent of patients with VAP died. The incidence index was 8.47 per 100 admissions to the ICU. VAP infections accounted for 46% of the overall count of device-associated healthcare-associated infections. Mechanical ventilation was used in 71 ± 8 patients during the 11 862 patient days and 8425 ventilation days. The rate of VAP per 1000 ventilator days was 11.15/9.34 /10.23 in years 2012/2013/2014 (half a year), respectively. The main VAP pathogens were Acinetobacter baumannii (45%) and Pseudomonas aeruginosa (17%). CONCLUSION During the reported time span, the incidence of VAP was lower than in the INICC report (2007-2012), but it was tenfold higher than in the NHSN/CDC report (dated 2012). Because of the unchanged VAP level during the 2.5-year observation period, the root cause needs to be determined and action should be taken to resolve this issue.

Results of the severe sepsis registry in intensive care units in Poland from 2003−2009

BACKGROUND Severe sepsis remains the most common cause of death in intensive care units (ICUs) according to many epidemiological studies. There are no data in Poland on the extent of severe sepsis cases treated in ICUs. The aim of the study was to analyse the course and outcome of severe sepsis patients treated in Polish ICUs. METHODS In 2003, the internet-based severe sepsis registry was created as a multicentre observational research project. An online questionnaire was made accessible to ICUs participating in the study. Questionnaires were completed after the discharge of patients and included demographic data, clinical and microbiological information about the cause, course, treatment and outcome of septic patients. All data were given voluntarily and anonymously. RESULTS During the 7-year period (2003-2009), 4999 cases of severe sepsis were registered for analysis. The mean age of septic patients was 57 years, and the majority of the patients were men (58%). The mean length of stay in the ICU was 10 days. A significant decrease in the mortality rate was observed from 54% in 2003 and 56% in 2004 to 46% in 2009 (P < 0.05). Most of the patients were admitted to the ICU for surgical reasons (56%), and intra-abdominal infections predominated (49%). Severe sepsis patients were admitted to ICUs in critical condition, and the majority of them (89%) had 3 or more organs dysfunction. The APACHE II score on admission was 26 points. Community acquired infections were the most frequent cause of severe sepsis (53%). Most of the pathogens responsible for infection were Gram-negative bacteria (58%). Gram-positive bacteria were identified in 34% of patients and fungi in 16%. A positive blood culture was detected in 41% of patients. Vasopressors were administered to most of the patients (86%). There was a marked increase in the frequency of administering noradrenaline and a decrease in administering dopamine. Renal replacement therapy was applied in 22% of the patients, and there was a marked increase in this type of therapy in the last two years of the study period. CONCLUSIONS Patients with severe sepsis involved in the 7-year registry were critically ill in half of the cases because of intra-abdominal infections, and the majority of them had multi-organ dysfunction. The mortality of registered patients was high, but it significantly decreased during the observation time. Based on the results obtained from this voluntary registry, the authors conclude that mandated sepsis registries should be established in Polish hospitals to improve the strategy of diagnosing and managing this syndrome.

Analysis of Acinetobacter baumannii hospital infections in patients treated at the intensive care unit of the University Hospital, Wroclaw, Poland: a 6-year, single-center, retrospective study

Background Acinetobacter baumannii (AB) is one of the most frequently isolated strains of bacteria in intensive care unit (ICU) patients, which provides huge therapeutic problems due to its multidrug resistance (MDR). Patients and methods The overall purpose of the study was analysis of health care- associated infections in terms of the incidence of AB strain infections and the changing susceptibility of this strain within a 6-year observation (2011–2016). The study was carried out in an ICU of the University Hospital in Wroclaw (Poland). Results Among 589 isolated strains responsible for 540 health care-associated infections (21.2%) in 2549 ICU patients, AB was the pathogen in 183 (31%) cases. The incidence of AB infection amounted to 6.4/1000 patient-days. An increase was noted in the total number of hospital infections caused by AB strain from 16.5% and 3.39/1000 patient-days in 2011 to 41% and 9.64/1000 in 2016 (p=0.0003 and p=0.000, respectively). AB infections most frequently concerned ventilator-associated pneumonia (73.8%). AB was susceptible to colistin, amikacin, imipenem, meropenem, and ciprofloxacin in 100%, 10.7%, 12.3%, 11.5%, and 2.4% respectively, and it was characterized by MDR in 98.36% of the strains. Conclusion The study revealed a 3-fold increase in the incidence of AB strain infections, significant increase in the resistance to carbapenems in the observed period, and a very high MDR. The solution to this problem would be the implementation of a repair program aiming at inhibition of AB strain transmission, measures to prevent infections, and restricted use of antibiotics.

Effect of universal chlorhexidine decolonisation on the infection rate in intensive care patients

BACKGROUND Healthcare-associated infections (HAIs), particularly intensive care unit-acquired infections (HAI-ICU), are an important cause of morbidity and mortality in hospitals. Most of these infections are caused by multidrugresistant organisms. The results of recent studies have suggested that daily bathing with chlorhexidine (CHX)-universal decolonisation can prevent ICU infections. The purpose of the study was to determine the influence of CHX bathing on the rate and type of HAI-ICU in critically ill patients. METHODS This observational study, conducted in a mixed, 16-bed tertiary ICU, compared the following three 3-month periods: I) pre-intervention (traditional soap-water bathing), II) intervention (bathing with 2% CHX clothes), and III) post-intervention (soap-water bathing). The type and rate of HAI-ICU were registered according to the European Centre for Disease Prevention and Control (ECDC) guidelines. RESULTS A total of 272 patients were included in the study. During the intervention period, the total infection rate was significantly lower than in the pre-intervention period (12.7% vs 22.2%, respectively). Significant decreases in the rate and density of catheter-related infections (CRI) were observed during the intervention period. A decrease in the isolation rate of multidrug-resistant bacteria was also observed during the intervention and post-intervention periods. CONCLUSIONS Daily bathing of ICU patients with chlorhexidine-impregnated clothes significantly decreased the rate of HAI-ICU and the acquisition of CRI. This simple hygienic approach can be an important adjunctive intervention with the capability of reducing the burden of healthcare-associated infections in ICUs.

Catheter-associated blood stream infections in an intensive care unit of a University Hospital in Wroclaw – International Nosocomial Infection Control Consortium’s findings

Central line-associated blood stream infections (CLA-BSI) are serious and potentially possible to reduce complication of hospitalization in severely ill patients. A prospective study (01.01.2012–30.06.2014) was conducted in the 20-bed ICU of the University Hospital in Wroclaw. The frequency and etiology of central line-associated blood stream infections were estimated in patients of the ICU according to the INICC project. Among 1097 patients CLA-BSI were diagnosed at 40. The incidence index was 3.64/100 admissions to the ICU. CLA-BSI were 19% of the overall count of device-associated healthcare-associated infections. Central-line was used at 89.92±4% patients during 11862 patient-days and 10684 central line-days. The density of CLA-BSI/1000 catheter-days was 3.77/3.36/0.0 accordingly in years 2012, 2013, 2014 (half a year). The main pathogens of catheter-associated blood stream infections were CN staphylococci (22%), Staphylococcus aureus (21%), Enterobacteriaceae (29%). In the observed period of time the incidence of CLA-BSI was lower than in the INICC report, but higher than in the NHSN/CDC report.