C. von Eiff

New aspects in the molecular basis of polymer-associated infections due to staphylococci.

Abstract Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, cause the majority of infections associated with both temporarily inserted and permanently implanted foreign bodies. In recent years, the pathogenesis of polymer-associated staphylococcal infection has become better understood, due in part to the characterization of further associated factors. The bacterial factors involved in the two phases of biofilm formation, i.e. the rapid adherence of bacteria to the polymer surface and the subsequent, more prolonged, accumulation phase, are presented in this review. The biofilm present on infected devices plays an important role in the pathogenicity of the infecting organism by protecting the embedded staphylococci and reducing the efficacy of host defenses and antimicrobial killing.

Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL‐6 in nasal epithelial cells in vitro

To cite this article: Sachse F, Becker K, von Eiff C, Metze D, Rudack C. Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL‐6 in nasal epithelial cells in vitro. Allergy 2010; 65: 1430–1437.

Cross-border comparison of the admission prevalence and clonal structure of meticillin-resistant Staphylococcus aureus

Since patient exchange between hospitals sharing a common catchment area might favour regional spread of meticillin-resistant Staphylococcus aureus (MRSA), the reliable detection of patients colonised at admission is crucial. Thus, hospitals in the Dutch-German border area EUREGIO MRSA-net aim at synchronising their local MRSA standards in order to prevent unidentified inter-hospital as well as cross-border spread. This assumes enhanced knowledge of MRSA prevalence and risk factors associated with MRSA carriage at admission. We conducted nasal MRSA screening of all inpatients admitted to 39 German hospitals (in the period 1 November to 30 November 2006) and to one Dutch hospital (in the period 1 July to 30 September 2007) in the EUREGIO MRSA-net. A total of 390 MRSA cases were detected among 25,540 patients screened. The admission prevalence was 1.6 MRSA/100 patients (6.5% of all S. aureus) in the German and 0.5 MRSA/100 patients (1.4% of all S. aureus) in the Dutch part of the border region. Overall, the predominating S. aureus protein A gene (spa) sequence types were t003, t032 and t011. One isolate (t044) carried Panton-Valentine leukocidin (PVL) encoding genes. Altogether, 79% and 67% of all MRSA patients in the German and Dutch regions respectively, were identifiable by the classical nosocomial risk factors assessed. In patients lacking all risk factors assessed, spa types t011 and t034 were predominant (P<0.001).

Emerging Staphylococcus species as new pathogens in implant infections

The vast use of prosthetic materials in medicine over the last decades has been accompanied by the appearance of new opportunistic pathogens previously considered incapable of causing infections with significant morbidity and/or mortality. In this regard, the genus Staphylococcus enlisting numerous species usually characterized by a saprophytic habit covers a special role. Apart from Staphylococcus aureus and Staphylococcus epidermidis, well known for their large prevalence in implant-related infections, a number of further staphylococcal species are progressively being indicated for their pathogenic potential. The increasing attention on these opportunistic bacteria is due to an ever growing number of clinical reports, which is also deriving from a more accurate identification of these species with currently available techniques. This synopsis intends to offer an overview on recently emerging coagulase-negative staphylococci (CoNS) as well as coagulase-positive/-variable staphylococci exhibiting distinct traits of virulence, pathogenicity, and epidemiologic impact depending among others on the medical field, the type of prosthetic device and its anatomic location.

Basic aspects of the pathogenesis of staphylococcal polymer-associated infections

Staphylococci are among the most frequently isolated microorganisms in clinical microbiology laboratories. Reports on surveillance data taken from the National Nosocomial Infections Surveillance System during the late 1980s and early 1990s indicated that Staphylococcus aureus, as well as coagulase-negative staphylococci (CONS), arc among the five most commonly reported pathogens in hospitals conducting hospital-wide surveillance [1,2]. S. aureus is one of the most feared pathogens, causing severe morbidity and often rapidly fatal infections. Infections due to these gram-positive cocci are often acute and pyogenic and, if untreated, may spread to surrounding tissue or, via bacteremia, to metastatic sites in other organs [3, 4]. CoNS are distinguished from S. aureus by their inability to produce free plasma coagulase. Currently, out of more than 30 coagulase-negative staphylococcal species, 12 are found mainly in specimens of human origin [5]. Because of their high prevalence on human skin and mucous membranes and their relatively low virulence, one of the major problems facing the laboratory is to distinguish clinically significant, pathogenic strains of CoNS from concomitant strains [5]. In recent years staphylococci, particularly CONS, have become important nosocomial pathogens and frequently cause infections associated with implanted foreign bodies. A wide spectrum of bacteria can be involved in this type of infection, however, staphylococci are by far the most frequently isolated group of bacteria. A battery of virulence factors involved in the pathogenesis of polymerassociated staphylococcal infection has been defined and characterized during the last few years and these findings will be presented in the following section.

Detection of Staphylococcus aureus by 16S rRNA directed in situ hybridisation in a patient with a brain abscess caused by small colony variants

A 45 year old man was admitted to hospital with a right sided facial paralysis and three month history of seizures. Computed tomography showed a left temporal mass including both intracerebral and extracerebral structures. Ten years earlier the patient had undergone a neurosurgical intervention in the same anatomical region to treat a subarachnoid haemorrhage. In tissue samples and pus obtained during neurosurgery, Staphylococcus aureus was detected by a 16S rRNA-directed in situ hybridisation technique. Following long term cultivation, small colony variants (SCV) of methicillin resistant S aureus were identified. The patient was treated successfully with a combination of vancomycin and rifampin followed by prolonged treatment with teicoplanin, with no sign of infection on follow up nine months after discharge. This is the first report in which S aureus SCV have been identified as causative organisms in a patient with brain abscess and in which in situ hybridisation has been used to detect S aureus in a clinical specimen containing SCV. Antimicrobial agents such as rifampin which have intracellular activity should be included in treatment of infections caused by S aureus SCV.

Distribution of macrolide-resistance genes in Staphylococcus aureus blood-culture isolates from fifteen German university hospitals.

Abstract The purpose of the study was to analyze the distribution of the macrolide-resistance genes in 134 erythromycin-resistant Staphylococcus aureus blood-culture isolates collected at 15 German university hospitals. The most prevalent resistance gene was ermC (68/134; 50.7%), followed by ermA (52/134; 38.8%), ereB (10/134; 7.5%), and mrsA/msrB (4/134; 6%). The least common genes were ermB (3/134; 2.2%) and ereA (1/134; 0.7%). Overall, resistance to erythromycin was predominantly due to the presence of two erm genes, although with different distributions, depending on the methicillin-resistance pattern.

Survey of staphylococcal enterotoxin genes, exfoliative toxin genes, and toxic shock syndrome toxin 1 gene in non-Staphylococcus aureus species

Abstract The aim of this study was to analyze the presence of staphylococcal exotoxin genes in staphylococci other than Staphylococcus aureus. Whereas for Staphylococcus aureus a large spectrum of different exotoxins responsible for toxin-mediated diseases has been described, only few and conflicting data are available regarding toxin production in all other staphylococcal species. A collection of clinical non-Staphylococcus aureus staphylococcal isolates were systematically screened for the presence of genes for toxic shock syndrome toxin 1, exfoliative toxins, and classical enterotoxins by using multiplex polymerase chain reaction enzyme immunoassays. In a total of 461 isolates of 18 different (sub)species derived from clinical specimens, no toxin gene sequences were amplified. The results indicate that the occurrence of toxin genes involved in staphylococcal toxin-mediated diseases is at least very rare in human-derived isolates of non-Staphylococcus aureus species.

Induction of CXC chemokines in A549 airway epithelial cells by trypsin and staphylococcal proteases − a possible route for neutrophilic inflammation in chronic rhinosinusitis

While various microorganisms have been recovered from patients with chronic rhinosinusitis, the inflammatory impact of virulence factors, in particular proteases from Staphylococcus aureus and coagulase negative staphylococci on the nasal epithelium, has not yet been investigated. Expression of CXC chemokines was determined in the epithelium of patients with chronic rhinosinusitis by immunohistochemistry. In a cell culture system of A549 respiratory epithelial cells, chemokine levels were quantified by enzyme‐linked immunosorbent assay (ELISA) after stimulation with supernatants originating from three different staphylococcal strains or with trypsin, representing a serine protease. Inhibition experiments were performed with prednisolone, with the serine protease inhibitor 4‐(2‐aminoethyl)‐benzenesulphonylfluoride (AEBSF) and with the nuclear transcription factor (NF)‐κΒ inhibitor (2E)‐3‐[[4‐(1,1‐dimethylethyl)phenyl]sulphonyl]‐2‐propenenitrite (BAY) 11–7085. Electromobility shift assays (EMSA) were used to demonstrate NF‐κB‐dependent protein synthesis. CXC chemokines interleukin (IL)‐8, growth‐related oncogene alpha (GRO‐α) and granulocyte chemotactic protein‐2 (GCP‐2) were expressed in the patients’ epithelium whereas epithelial cell‐derived neutrophil attractant 78 (ENA‐78) was rarely detected. In A549 cells, chemokines IL‐8, ENA‐78 and GRO‐α but not GCP‐2 were induced by trypsin and almost equal levels were induced by staphylococcal supernatants. IL‐8, GRO‐α and ENA‐78 synthesis was suppressed almost completely by AEBSF and BAY 11–7085, whereas prednisolone reduced chemokine levels differentially dependent on the supernatant added. CXC chemokines were detectable in the epithelium of patients with chronic rhinosinusitis. Staphylococcal serine proteases induced CXC chemokines in A549 cells, probably by the activation of proteases activated receptors, and thus might potentially be involved in neutrophilic inflammation in chronic sinusitis.

Prospective, non-interventional, multi-centre trial of tigecycline in the treatment of severely ill patients with complicated infections: new insights into clinical results and treatment practice.

Background: Only few data are available on the efficacy of tigecycline in critically ill patients. Methods: This prospective, multicenter, non-interventional study investigated the efficacy and safety of tigecycline in hospitalized, severely ill patients with complicated intra-abdominal infections (cIAI) and/or complicated skin and soft tissue infections (cSSTI). Documentation included diagnosis, clinical findings, Acute Physiology and Chronic Health Evaluation II score, laboratory assessments, surgery, clinical outcomes, and adverse events. Results: Six hundred and fifty-six patients (mean Acute Physiology and Chronic Health Evaluation II score 19.1) with cIAI (41%), cSSTI (16%), multiple infection sites (13%) and/or other severe infections (31%) received tigecycline – 51% as monotherapy – due to failure of previous antibiotics (55%) or since resistant pathogens were suspected or proven (45%); clinical cure/improvement rates were 75, 82, 76 and 67% for cIAI, cSSTI, other severe infections and multiple infection sites, respectively. Drug-related adverse events occurred in 6.7% of patients. Conclusions: The efficacy and safety of tigecycline was demonstrated in a population of severely ill patients with complicated infections.