Thilo Busch

Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing Klebsiella pneumoniae: a single-centre experience

After a single patient was transferred to Leipzig University Hospital from a hospital in Rhodes, Greece, the hospital experienced the largest outbreak due to a KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) strain thus far observed in Germany. Ninety patients hospitalised between July 2010 and October 2012 were affected. In an attempt to eliminate KPC-2-KP from their digestive tracts, 14 consecutive patients (16%) were treated with a short course (7 days) of selective digestive decontamination (SDD), employing colistin (1 million units q.i.d.) and gentamicin (80 mg q.i.d.) as oral solutions, and applying colistin/gentamicin gel (0.5 g) to the oral cavity. In a retrospective analysis, these 14 SDD patients were compared with the remaining 76 patients harbouring KPC-2-KP. KPC-2-KP carrier status was followed in all 14 SDD patients by submitting stool samples to KPC-specific PCR. The mean follow-up period was 48 days (range 12-103 days). Successful elimination of KPC-2-KP was defined as a minimum of three consecutive negative PCR test results separated by ≥48 h each. Decolonisation of KPC-2-KP was achieved in 6/14 patients (43%) after a mean of 21 days (range 12-40 days), but was also observed in 23/76 (30%) of the non-SDD controls (P = 0.102). SDD treatment resulted in the development of secondary resistance to colistin (19% increase in resistance rate) and gentamicin (45% increase) in post-treatment isolates. In the control group, no secondary resistance occurred. We conclude that the SDD protocol applied in this study was not sufficiently effective for decolonisation and was associated with resistance development.

Colonization of liver transplant recipients with KPC-producing Klebsiella pneumoniae is associated with high infection rates and excess mortality: a case–control analysis

PurposeFrom mid-2010 to early 2013 there was a large single-center (Leipzig University Hospital, Germany) outbreak of Klebsiella pneumoniae carbapenemase (KPC) type 2 producing K. pneumoniae (KPC-2-KP) involving a total of 103 patients. The aim of this study was to compare KPC-positive liver transplant recipients (LTR) and KPC-negative controls to determine both the relative risk of infection following colonization with KPC-2-KP and the case fatality rate associated with KPC-2-KP.MethodsThe study cohort of this retrospective observational study comprised nine patients who had undergone orthotopic liver transplantation (LTx) (median age of 52xa0years, range 28–73 years) with confirmed evidence of colonization with KPC-2-KP. The data from these nine LTR were matched to 18 LTR (1:2) in whom carbapenem-resistant pathogens were not present and compared for clinical outcomes.ResultsOf these nine cases, eight (89xa0%) progressed to infection due to KPC-2-KP, and five (56xa0%) were confirmed to have bloodstream infection with KPC-2-KP. Matched-pair analysis of KPC-positive LTR and KPC-negative controls revealed a substantially increased relative risk of 7.0 (95xa0% confidence interval 1.8–27.1) for fatal infection with KPC-2-producing K. pneumoniae after transplantation with a mortality rate of 78xa0% (vs. 11xa0%, pxa0=xa00.001).ConclusionsColonization with KPC-2-KP in LTR leads to high infection rates and excess mortality. Therefore, frequent screening for carbapenem-resistant bacteria in patients on LTx waiting lists appears to be mandatory in an outbreak setting. Patients with evidence of persistent colonization with KPC-producing pathogens should be evaluated with extreme caution for LTx.

Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae after a large single-center outbreak in Germany.

BACKGROUNDnThe natural progress of intestinal colonization with Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae (KPC-2-KP) is almost unknown.nnnMETHODSnAfter a large, single-center outbreak of KPC-2-KP, we analyzed carrier prevalence through retrospective and prospective investigation of intestinal KPC-2-KP carriage 1 month, 3 months, 6 months, 1 year, and 2 years after acquisition, defined as the earliest date of KPC-2-KP detection. Rectal swabs or stool samples were collected at baseline and at each visit and submitted for both culture and KPC-specific polymerase chain reaction. Resolution of intestinal KPC-2-KP carriage was defined as a minimum of 3 consecutive negative polymerase chain reaction test results separated by at least 48 hours.nnnRESULTSnIn patients available for long-term evaluation 26 out of 84 patients (31%) tested negative for KPC-2-KP after 1 month, 14 out of 34 (41%) after 3 months, 17 out of 26 (65%) after 6 months, 14 out of 19 (74%) after 1 year, and 5 out of 6 (83%) after 2 years. Decolonization of KPC-2-KP was hampered in patients with prolonged or repeated hospitalization (P = .044-.140, depending on the time interval). Two patients retested positive for KPC-2-KP after they had previously shown 3 consecutive negative tests. The longest positive KPC-2-KP carrier status so far was observed after nearly 40 months (1,191 days).nnnCONCLUSIONSnThe majority of patients experienced spontaneous decolonization within 6 months after acquisition, mainly after discharge from the hospital. However, long-term carriage of >3 years is possible. Appropriate infection control measures must be taken when these patients are readmitted to health care facilities. A series of at least 4 consecutive negative rectal swabs or stool samples separated by sufficient time intervals appears necessary before the declaration of successful KPC-2-KP decolonization is made.

Obesity in anesthesia and intensive care.

Obesity is a global epidemic increasingly affecting management of anesthesia as well as intensive care medicine. Possible improvements in therapy require consideration of the specific pathophysiology of the obese, their concomitant diseases, and the complications associated with morbid obesity. Systematic assessment of perioperative risk factors is essential for an appropriate management. Paradoxically, overweight and moderately obese patients undergoing surgery have a lower risk when compared to patients with normal weight. The highest mortality and morbidity rates in this setting are reported for underweight and morbidly obese patients. The better chance of survival when compared to normal-weight individuals in the perioperative setting has been described the obesity paradox. In particular, the commitment of all involved physicians to improve all aspects of care will reduce the perioperative risk in obese patients. Physiological and pharmacological characteristics of the obese should also be considered. Furthermore, adequate technical equipment and practical skills of all members of the anesthesia team significantly contribute to risk reduction and therapeutic success in obese patients.

Restrictive transfusion practice during extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome.

Recommendations concerning the management of hemoglobin levels and hematocrit in patients on extracorporeal membrane oxygenation (ECMO) still advise maintenance of a normal hematocrit. In contrast, current transfusion guidelines for critically ill patients support restrictive transfusion practice. We report on a series of patients receiving venovenous ECMO (vvECMO) for acute respiratory distress syndrome (ARDS) treated according to the restrictive transfusion regimen recommended for critically ill patients. We retrospectively analyzed 18 patients receiving vvECMO due to severe ARDS. Hemoglobin concentrations were kept between 7 and 9 g/dL with a transfusion trigger at 7 g/dL or when physiological transfusion triggers were apparent. We assessed baseline data, hospital mortality, time on ECMO, hemoglobin levels, hematocrit, quantities of packed red blood cells received, and lactate concentrations and compared survivors and nonsurvivors. The overall mortality of all patients on vvECMO was 38.9%. Mean hemoglobin concentration over all patients and ECMO days was 8.30 ± 0.51 g/dL, and hematocrit was 0.25 ± 0.01, with no difference between survivors and nonsurvivors. Mean numbers of given PRBCs showed a trend towards higher quantities in the group of nonsurvivors, but the difference was not significant (1.97 ± 1.47 vs. 0.96 ± 0.76 units; P = 0.07). Mean lactate clearance from the first to the third day was 45.4 ± 28.3%, with no significant difference between survivors and nonsurvivors (P = 0.19). In our cohort of patients treated with ECMO due to severe ARDS, the application of a restrictive transfusion protocol did not result in an increased mortality. Safety and feasibility of the application of a restrictive transfusion protocol in patients on ECMO must further be evaluated in randomized controlled trials.

Is perioperative low molecular weight hydroxyethyl starch infusion a risk factor for delayed graft function in renal transplant recipients

BACKGROUNDnCrystalloid or colloid fluids may be utilized during kidney transplantation. Histopathological and clinical data indicate that hydroxyethyl starch (HES) may have nephrotoxic potential.nnnMETHODSnThis retrospective single-centre cohort study screened 192 and included 113 patients who underwent renal transplantation between 2003 and 2007 at University of Leipzig Medical Faculty, Germany. The primary outcome parameter was delayed graft function (DGF). Patients were divided into two groups. Patients in group CRYS (N = 73) received crystalloid solution (acetated Ringers or normal saline) only. Patients in the group HES (N = 40) received a minimum of 500 mL 6% HES 130/0.4 and additional crystalloid solution by discretion of the transplant team.nnnRESULTSnPatients in both groups did not differ with respect to demographic data and American Society of Anesthesiologists Physical Status Classification System scores, except for the donor age, which was significantly lower in the group HES. The rate of DGF was not found to be different in group CRYS (31.5%) when compared to group HES (32.5%) (P = 1.00, n.s.).nnnCONCLUSIONnIn this single-centre retrospective cohort study, infusion of low molecular weight 6% HES 130/0.4 during and after renal transplantation was found to have no significant negative effect upon the rate of DGF.

Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study

Background Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance. Methods Patients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH). Results Among 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1–1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates. Conclusions Enterococci and Candida species play an important role in the microbial colonization of biliary stents. Therefore, empirical antimicrobial treatment of stent-associated cholangitis should be guided toward enterococci, Enterobacteriaceae, streptococci, anaerobes, and Candida. To determine causative pathogens, an accurate microbiological analysis of the extracted stent(s) may be helpful.

Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice

BackgroundInhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it’s biochemical mechanisms and effects on inflammatory reactions.MethodsMice (C57BL/6; nu2009=u200986) received lipopolysaccharide (LPS, 30xa0mg/kg) intraperitoneally and subsequently breathed 50xa0ppm CO continuously during defined intervals of 3, 6, 12 or 18xa0h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO2u2009=u20090.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured.ResultsHPV was impaired after LPS-challenge (pu2009<u20090.01). CO exposure restored HPV-responsiveness if administered continuously for full 18xa0h, for the first 6xa0h and if given in the interval between the 3rd and 6th hour after LPS-challenge (pu2009<u20090.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (pu2009<u20090.05). We found no effects on inflammatory plasma cytokines.ConclusionLow-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

Mechanical complications and outcomes following invasive emergency procedures in severely injured trauma patients

This study aimes to determine the complication rates, possible risk factors and outcomes of emergency procedures performed during resuscitation of severely injured patients. The medical records of patients with an injury severity score (ISS) >15 admitted to the University Hospital Leipzig from 2010 to 2015 were reviewed. Within the first 24u2009hours of treatment, 526 patients had an overall mechanical complication rate of 26.2%. Multivariate analysis revealed out-of-hospital airway management (OR 3.140; 95% CI 1.963–5.023; pu2009<u20090.001) and ISS (per ISS point: OR 1.024; 95% CI 1.003–1.045; pu2009=u20090.027) as independent predictors of any mechanical complications. Airway management complications (13.2%) and central venous catheter complications (11.4%) were associated with ISS >32.5 (pu2009<u20090.001) and ISS >33.5 (pu2009=u20090.005), respectively. Chest tube complications (15.8%) were associated with out-of-hospital insertion (pu2009=u20090.002) and out-of-hospital tracheal intubation (pu2009=u20090.033). Arterial line complications (9.4%) were associated with admission serum lactate >4.95u2009mmol/L (pu2009=u20090.001) and base excess <−4.05u2009mmol/L (pu2009=u20090.008). In multivariate analysis, complications were associated with an increased length of stay in the intensive care unit (pu2009=u20090.019) but not with 24u2009hour mortality (pu2009=u20090.930). Increasing injury severity may contribute to higher complexity of the individual emergency treatment and is thus associated with higher mechanical complication rates providing potential for further harm.

Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung

Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the mechanism of this action remains unknown. It has been postulated that carbonic anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO) from nitrite and that this formation is increased in the presence of acetazolamide. Acetazolamide reduces HPV in pigs without evidence of any NO generation, whereas nebulized sodium nitrite reduces HPV by NO formation; however; combined infusion of acetazolamide with sodium nitrite inhalation did not further increase exhaled NO concentration over inhaled nitrite alone in pigs exposed to alveolar hypoxia. We conclude that acetazolamide does not function as either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and probably other mammals, to explain its vasodilating actions in the pulmonary or systemic circulations.