Authors:Orsolya Benedek, Andreas Podbielski, and Philipp Warnke
Chemiluminescent or enzyme-linked fluorescent immunoassays are commonly used to diagnose Clostridium difficile-associated diarrhea.
The LIAISON analyzer (DiaSorin, Italy) was compared to miniVIDAS (bioMérieux, France) and, furthermore, to culture of toxigenic strains. In total, 249 native stool samples were analyzed. Sensitivities, specificities, and positive and negative predictive values were investigated. Furthermore, performance under routine conditions was assessed.
The glutamate dehydrogenase chemiluminescent immunoassay (GDH-CLIA) assay revealed a high sensitivity and negative predictive value. The toxins A&B assays exhibited approximately the same low sensitivity and high specificity. Technical drawbacks experienced with the LIAISON analyzer in 48% of the analyses considerably delayed the time to the first diagnostic report and interfered with laboratory routine workflow.
The analytical performance of the investigated platforms should be reflected in the context of implementation into the laboratory workflow.
Authors:Philipp Warnke, Thomas Köller, Paul Stoll, and Andreas Podbielski
We report the case of a nosocomial infection due to Enterococcus cecorum isolated from a blood culture of a 75-year-old septic male patient. Matrix-assisted laser desorption–ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Vitek 2 succeeded in identification of the isolate.
Authors:Lennart Bartolitius, Hagen Frickmann, Philipp Warnke, Peter Ottl, and Andreas Podbielski
A nose model that allows for the comparison of different modes of sample acquisition as well as of nasal swab systems concerning their suitability to detect defined quantities of intranasal microorganisms, and further for training procedures of medical staff, was evaluated.
Based on an imprint of a human nose, a model made of a silicone elastomer was formed. Autoclave stability was assessed. Using an inoculation suspension containing Staphylococcus aureus and Staphylococcus epidermidis, the model was compared with standardized glass plate inoculations. Effects of inoculation time, mode of sampling, and sample storage time were assessed.
The model was stable to 20 autoclaving cycles. There were no differences regarding the optimum coverage from the nose and from glass plates. Optimum sampling time was 1 h after inoculation. Storage time after sampling was of minor relevance for the recovery. Rotating the swab around its own axis while circling the nasal cavity resulted in best sampling results.
The suitability of the assessed nose model for the comparison of sampling strategies and systems was confirmed. Without disadvantages in comparison with sampling from standardized glass plates, the model allows for the assessment of a correct sampling technique due to its anatomically correct shape.
Authors:Hagen Frickmann, Caroline Klenk, Philipp Warnke, Sylvio Redanz, and Andreas Podbielski
Background: The effects of cell-free culture supernatants of probiotic Lactobacillus rhamnosus GG and Streptococcus salivarius K12 on replication and biofilm forming of Staphylococcus aureus and S. epidermidis were assessed in vitro.
Methods: S. aureus and S. epidermidis strains were exposed to cell-free culture supernatants of L. rhamnosus GG and S. salivarius K12 at different concentrations starting at 0, 4, and 24 h after the onset of incubation. Bacterial amplification was measured on microplate readers, as well as biofilm growth after safranine staining. Scanning electron microscopy was performed for visualization of biofilm status.
Results: The S. salivarius K12 culture supernatant not only reduced or prevented the formation and maturation of fresh biofilms but even caused a reduction of preformed S. epidermidis biofilms. The L. rhamnosus GG culture supernatant did not show clear inhibitory effects regardless of concentration or time of addition of supernatant, and even concentration-depending promotional effects on the planktonic and biofilm growth of S. aureus and S. epidermidis were observed.
Conclusion: In particular, the inhibitory effects of the S. salivarius K12 culture supernatant on the formation of staphylococcal biofilms are of potential relevance for biofilm-associated diseases and should be further assessed by in vivo infection models.
Authors:H. Frickmann, A. Podbielski, A. Essig, N. G. Schwarz, and Andreas Erich Zautner
Diagnostic misidentifications of commensalic Haemophilus haemolyticus as pathogenic Haemophilus influenzae are frequent. This pilot study evaluates whether isolations of H. haemolyticus are frequent enough in Germany to cause a relevant diagnostic problem, considering the fact that even H. influenzae is a mere colonizer in about 30% of isolations.
In microbiological laboratories of two hospitals located in Northern and Southern Germany, the distribution of Haemophilus spp. was analyzed during a six-month-period. Site of infection, sex, and age of the patients was taken into consideration.
A total of 77 Haemophilus spp. isolates was acquired and discriminated on species level, comprising: 48 H. influenzae, 25 Haemophilus parainfluenzae, 3 H. haemolyticus, and 1 Haemophilus parahaemolyticus. The proportion of H. haemolyticus was calculated to range between 1.2% and 16.2 % within the 95% confidence limits. Commensalic Haemophilus spp. were isolated from oropharynx-associated sites only. H. influenzae, in contrast, was detected in clinically relevant materials like lower respiratory materials and conjunctiva swabs.
Altogether, there was a low proportion of clinical H. haemolyticus isolates. Accordingly, the problem of unnecessary antibiotic therapies due to misidentifications of H. haemolyticus as H. influenzae is quantitatively negligible compared with the risk of confusing H. influenzae colonizations with infections.
Authors:Andreas Hahn, Andreas Podbielski, Markus M. Heimesaat, Hagen Frickmann, and Philipp Warnke
Surrogate endpoints are widely used in clinical trials, especially in situations where the endpoint of interest is not directly observable or to avoid long trial periods. A typical example for this case is frequently found in clinical trials in oncology, where overall survival (OS) as endpoint of interest and progression free survival (PFS) as surrogate endpoint are discriminated.
Based on the perspective of case definitions on surrogate endpoints, we provide a formal definition of such endpoints followed by a description of the structure of surrogate endpoints.
Surrogate endpoints can be considered as case definitions for the endpoint of interest. Therefore, the performance of surrogate endpoints can be described using the classical terminology of diagnostic tests including sensitivity and specificity. Since such endpoints always focus on sensitivity with necessarily reduced specificity, efficacy estimates based on such endpoints are in general biased.
The abovementioned has to be taken into account while interpreting the results of clinical trials and should not be ignored while planning or conducting a study.
Authors:Hagen Frickmann, Wibke Schmeja, Emil Reisinger, Thomas Mittlmeier, Karen Mitzner, Norbert Georg Schwarz, Philipp Warnke, and Andreas Podbielski
This study assessed protective effects of a continuous introduction of safe instruments in terms of reduction of needle stick injuries. The retrospective study analyzed correlations between the increasing proportion of safe instruments and a reduction of the incidence of needle stick injuries linked to such instruments in a German university hospital over 5 years. Incidents declined about 17.6% from 80.3 incidents per 1000 employees to 66.2, associated with an increase in the proportions of injuries due to instruments without protective mechanisms such as scalpels or hypodermic needles by 12.2%. For injuries due to venipuncture cannulae in various surgical and internal medicine departments, there was a negative association between the proportion of safe instruments and the incidence of injuries. For injection needles, portacath needles, and lancets in selected internal medicine departments, the number of injuries also dropped during this study interval. However, there was no clear-cut association with the percentage of safe instruments. This observational study suggests a correlation between the implementation of use of safe instruments and the reduction of needle stick injuries in a case of a graduated implementation. However, the effects are much less pronounced than in previous interventional studies.
Authors:Heike Granzer, Ralf Matthias Hagen, Philipp Warnke, Wolfgang Bock, Tobias Baumann, Norbert Georg Schwarz, Andreas Podbielski, Hagen Frickmann, and Thomas Koeller
This study addressed carbapenem-resistant Acinetobacter baumannii complex (ABC) isolates from patients that were injured during the military conflict in the Eastern Ukraine and treated at German Armed Forces Hospitals in 2014 and 2015. Clonal diversity of the strains and potential ways of transmission were analyzed.
Patients with one or several isolation events of carbapenem-resistant ABC were included. Isolates were characterized by VITEK II-based identification and resistance testing, molecular screening for frequent carbapenemase genes, and DiversiLab rep-PCRbased typing. Available clinical information of the patients was assessed.
From 21 young male Ukrainian patients with battle injuries, 32 carbapenem- and fluoroquinolone-resistant ABC strains were isolated. Four major clonal clusters were detected. From four patients (19%), ABC isolates from more than one clonal cluster were isolated. The composition of the clusters suggested transmission events prior to the admission to the German hospitals.
The infection and colonization pressure in the conflict regions of the Eastern Ukraine with ABC of low clonal diversity is considerable. Respective infection risks have to be considered in case of battle-related injuries in these regions. The low number of local clones makes any molecular exclusion of transmission events difficult.
Authors:Hagen Frickmann, Kerstin Köller, Irina Veil, Mirjam Weise, Alicja Ludyga, Norbert Georg Schwarz, Philipp Warnke, and Andreas Podbielski
This study assesses the clinical relevance of vancomycin-susceptible enterococci in bacteremic patients and compares it with bacteremia due to Staphylococcus aureus and Escherichia coli.
During a 5-year-study interval, clinical and diagnostic features of patients with enterococcal bacteremia were compared to those of patients with E. coli or S. aureus bacteremia. Each patient was only counted once per hospital stay.
During the 5-year study interval, data from 267 patients with enterococcal bacteremia and from 661 patients with bacteremia due to E. coli or S. aureus were evaluated. In spite of a comparable risk of death, patients with enterococci more frequently needed catecholamines and invasive ventilation. Furthermore, enterococci were more frequently associated with a mixed bacterial flora in bloodstream infections. While fatal sepsis due to E. coli and S. aureus was associated with typical shock symptoms, this association was not confirmed for enterococci.
Although enterococcal bacteremia is associated with a risk of dying comparable to that with bacteremia due to E. coli and S. aureus, a lower pathogenic potential of enterococci in bloodstream has to be acknowledged. Enterococci in the bloodstream are more likely to be an epiphenomenon of impending death than its major cause.
Authors:Hagen Frickmann, Andreas Hahn, Stefan Berlec, Johannes Ulrich, Moritz Jansson, Norbert Georg Schwarz, Philipp Warnke, and Andreas Podbielski
Introduction: Escherichia coli and Staphylococcus aureus are important causes of severe diseases like blood stream infections. This study comparatively assessed potential differences in their impact on disease severity in local and systemic infections.
Methods: Over a 5-year interval, patients in whom either E. coli or S. aureus was detected in superficial or primary sterile compartments were assessed for the primary endpoint death during hospital stay and the secondary endpoints duration of hospital stay and infectious disease as the main diagnosis.
Results: Significance was achieved for the impacts as follows: Superficial infection with S. aureus was associated with an odds ratio of 0.27 regarding the risk of death and of 1.42 regarding infectious disease as main diagnosis. Superficial infection with E. coli was associated with a reduced duration of hospital stay by −2.46 days and a reduced odds ratio of infectious diseases as main diagnosis of 0.04. The hospital stay of patients with E. coli was increased due to third-generation cephalosporin and ciprofloxacin resistance, and in the case of patients with S. aureus due to tetracycline and fusidic acid resistance.
Conclusions: Reduced disease severity of superficial infections due to both E. coli and S. aureus and resistance-driven prolonged stays in hospital were confirmed, while other outcome parameters were comparable.