Clinical efficacy of tigecycline used as monotherapy or in combination regimens for complicated infections with documented involvement of multiresistant bacteria.

INTRODUCTION: Tigecycline is an established treatment option for infections with multiresistant bacteria (MRB). It retains activity against many strains with limited susceptibility to other antibiotics. Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospective noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals. MATERIALS AND METHODS: Data on the full population have been published; our present analysis focuses on infections caused by MRB. The study population included patients with complicated infections, high disease severity (APACHE II > 15: 65 %) and high MRB prevalence. Most patients had comorbidities, including cardiovascular disease, renal insufficiency, and/or diabetes mellitus. Treatment success was defined as cure/improvement without requirement of further antibiotic therapy. RESULTS: Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus (MRSA), 42 vancomycin-resistant Enterococci (VRE) and 67 Gram-negative extended beta-lactamase (ESBL) producers. Of the MRB subpopulation, 140 patients received tigecycline monotherapy, 75 were treated with combination regimens. High overall clinical success rates were recorded for MRB infections treated with tigecycline alone (94 %) or in combinations (88 %); in detail intraabdominal infections (monotherapy: 90 %; combinations: 93 %), skin/soft tissue infections (93; 100 %), community-acquired pneumonia (100; 100 %), hospital-acquired pneumonia (94,7; 72,7 %), diabetic foot infections (89; 33 %), blood stream infections (100; 100 %) and multiple-site infections (92; 71 %). CONCLUSIONS: Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity. These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement.

[Persistent and recurrent skin and soft tissue infections by Staphylococcus aureus. Impact of the small colony-variant (SCV) phenotype and of Panton-Valentine leukocidin (PVL)-positive S. aureus isolates]. / Chronisch rezidivierende Infektionen der Haut und Weichgewebe durch Staphylococcus aureus. Klinische Bedeutung des Small-colony-variant (SCV)-Phänotyps und von Panton-Valentine-Leukozidin (PVL)-positiven S.-aureus-Isolaten.

Staphylococcus aureus is one of the major pathogens causing chronic skin and soft tissue infections. Particularly isolates producing Panton-Valentine leukocidin (PVL) comprising methicillin-susceptible and community-associated methicillin-resistant S. aureus (CA-MRSA) have been associated with more aggressive and persistent or relapsing courses. Beyond classical resistance mechanisms, functional resistance as shown by the small colony-variant (SCV) phenotype could be also responsible for treatment failures, despite the administration of antibiotics tested in vitro as susceptible. Also this phenotype has been associated with chronic courses of infections often with multiple exacerbations. Due to their ability to persist intracellularly, SCVs are protected from host defense and antibiotic treatment if only extracellularly active agents are administered. Reduced growth, abnormal colony morphology and changes in the metabolism of the SCVs aggravate drastically their identification, differentiation and susceptibility testing. The diagnostic and therapeutic challenges of PVL-positive and SCV isolates necessitate close collaboration with microbiological and infectious disease specialists.

Can risk area designation help increase vaccination coverage for Tick-Borne Encephalitis? Evidence from German claims data.

BACKGROUND AND OBJECTIVES: Although vaccine preventable, the incidence of tick-borne encephalitis (TBE) increased in Germany from 2001 to 2021 by on average 2% each year, with a peak of more than 700 TBE infections documented in 2020. TBE-risk areas, as designated by district based on incidence of human cases, expanded north- and northeastward, present in 11 of the 16 Federal States as of 2022. Using claims data from a German statutory health insurance in the Federal States of Saxony and Thuringia (AOK PLUS), we aimed to assess whether official assignment of a district to a risk area had an impact on vaccination rates in Germany. METHODS: The data covered the period from 01/01/2010 to 31/12/2018 and included information on vaccine administrations from outpatient physicians. Yearly incident vaccination rates were reported overall and by district. To investigate the association between a new designation of an incident TBE-risk area and vaccination rates, a difference-in-difference analysis was conducted. RESULTS: Overall, the incident vaccination rates increased from 6.2 to 9.5 per 1,000 person-years between 2012 and 2018, with a peak of 12.2 in 2015. While districts that had been risk-areas for the whole study period had always a higher vaccination rate compared to districts that were never categorized as risk areas, the increase between 2012 and 2018 was comparable in the two groups (3.0 and 3.2 per 1,000 person-years, respectively). In contrast, districts that were newly designated risk districts during the study period experienced a significantly larger increase in vaccination rates, going from 5.8 to 14.7 per 1,000 person-years between 2012 and 2018, with a peak of 19.6 in 2015. CONCLUSION: The results suggest that the new designation of a district as risk area has a significant positive impact on vaccination rates, which is strongest immediately after designation of risk area.

Resistance trends and in vitro activity of tigecycline and 17 other antimicrobial agents against Gram-positive and Gram-negative organisms, including multidrug-resistant pathogens, in Germany.

To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previous trials (German Tigecycline Evaluation Surveillance Trial, G-TEST I and II, performed in 2005 and 2007, respectively) conducted prior to and shortly after the introduction of tigecycline in Germany. Moreover, the in vitro activities of tigecycline against the subset of multidrug-resistant (MDR) pathogens recovered within all three sampling periods (n = 4,988) were evaluated in comparison to the corresponding non-MDR isolates. All susceptibility tests were performed by broth microdilution. Between 2005 and 2009, tigecycline retained its high activity against Gram-positive and Gram-negative organisms, including MDR pathogens. By contrast, an in part marked increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for many Enterobacteriaceae and for non-fermenting Gram-negative bacteria. Against a background of a steadily increasing number of multiresistant pathogens, the activity of tigecycline remained unaltered. With the exception of Acinetobacter isolates with decreased susceptibility to carbapenems, tigecycline's activity profile was not notably affected by organisms resistant to other drug classes and, thus, holds promise as an important therapeutic agent, particularly for situations in which MDR organisms are suspected.

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

BACKGROUND: Staphylococcus aureus has been associated with chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis but its role is still controversially discussed. Here, we demonstrate S. aureus detection in the mucosa of CRSwNP. In addition, intracellular residency of S. aureus in nasal polyp epithelial cells (NPECs) and its capability to induce TH-2 cytokines were analyzed in vitro. METHODS: Staphylococcus aureus detection in CRSwNP (n = 25), CRS without polyps (CRSsNP, n = 5), and turbinate mucosa (TM, n = 10) was performed by peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) and microbial cultivation from tissue biopsies. Intracellular residency was examined by intracellular persistence assay and electron microscopy. IL-6 and IL-13 responses to S. aureus infection and supernatants were quantified by ELISA. RESULTS: Peptide nucleic acid-fluorescence in situ hybridization positive bacterial cells were significantly increased in the epithelium of CRSwNP (17/25) compared to CRSsNP (0/5) and TM (1/10). Good concordance of PNA-FISH results and S. aureus cultivation was found applying Cohen's κ for CRSwNP (κ = 0.841) and TM (κ = 1.0). Intracellular persistence assay with S. aureus strain Newman and its corresponding small-colony variant mutant strain III33 demonstrated intracellular survival and replication of S. aureus within NPECs. Both S. aureus strains significantly induced IL-6 but not IL-13 in infected NPECs and in NPECs challenged with corresponding staphylococcal supernatants. CONCLUSION: Invasion of the epithelium by S. aureus was a phenomenon seen predominantly in CRSwNP. Regardless of an intra- or extracellular localization in the epithelium, S. aureus is capable to induce IL-6 synthesis in vitro and thus may contribute to the TH-2 cytokine pattern in CRSwNP.

Susceptibility of clinical isolates of frequently encountered bacterial species to tigecycline one year after the introduction of this new class of antibiotics: results of the second multicentre surveillance trial in Germany (G-TEST II, 2007).

Tigecycline, a broad-spectrum antibiotic for parenteral use, was introduced in Germany in May 2006. In the G-TEST-II trial, the susceptibility of isolates, recovered in 2007 from hospitalised patients in 15 centres, was assessed against tigecycline and comparators. Susceptibility tests were performed by the microdilution procedure. This study reports on the susceptibility of the isolates of 16 bacterial species and compares the results with those of a trial (G-TEST I) conducted prior to the introduction of tigecycline. Between 2005 and 2007, tigecycline retained activity against Gram-positive and Gram-negative organisms. By contrast, the rate of vancomycin-resistant strains among Enterococcus faecium isolates almost doubled. Moreover, an increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for members of the family Enterobacteriaceae. Against a background of a steadily rising number of pathogens that are resistant to various antibiotic classes, tigecycline represents an important treatment option.

Susceptibility of common aerobic pathogens to tigecycline: results of a surveillance study in Germany.

Tigecycline is a novel antimicrobial agent for parenteral use encompassing a broad spectrum of bacterial pathogens, including multi-resistant organisms. Here, we report the results of the first nationwide surveillance trial that was conducted in order to evaluate the susceptibility of bacterial isolates to tigecycline in a European country prior to its clinical use. A total of 2,610 Gram-positive and Gram-negative organisms recovered from hospitalized patients were tested. Minimum inhibitory concentrations (MICs) were determined using the microdilution method. All enterococci, staphylococci (including methicillin-resistant Staphylococcus aureus; MRSA), and streptococci tested were tigecycline-susceptible, except one isolate of Staphylococcus haemolyticus. Among the Gram-negative bacteria, 100% of the Escherichia coli isolates (including extended spectrum beta-lactamase [ESBL]-producers) were tigecycline-susceptible, while about 10% of the Enterobacter cloacae and Klebsiella pneumoniae isolates were resistant. Based on the results of this surveillance study, tigecycline may represent a suitable option most notably for the empiric treatment of bacterial mixed infections, including in clinical situations in which multi-resistant organisms are suspected.

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004.

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries.

CD4+ T cells transfer resistance against Citrobacter rodentium-induced infectious colitis by induction of Th 1 immunity.

Citrobacter rodentium induces an acute, self-limited colitis in mice which is histologically associated with crypt hyperplasia. The infection serves as a model for human infectious colitis induced by enteropathogenic Escherichia coli. We investigated if Balb/c mice, which had spontaneously cleared C. rodentium infection, were protected against re-infection and if resistance against intestinal infection can be systemically transferred using spleen cells. The course of infection was monitored by faecal excretion. Spleen cells, splenic CD3+ and CD4+ cells were transferred from resistant mice to non-infected recipients prior to infection. Cytokine secretion, serum and faecal antibody titres and histological disease severity were assessed. Balb/c mice were resistant against re-infection. The course of infection was shorter in mice receiving primed spleen cells, CD3+ and CD4+ cells. Transfer of CD4+ T cells from resistant mice induced gamma-interferon, interleukin (IL)-2 and IL-17 secretion and suppressed IL-10 secretion. Anti-Citrobacter serum IgG1 and IgG2a enzyme-linked immunosorbent assay OD levels were increased. Faecal IgA secretion was increased while serum IgA was suppressed in recipients of CD4+ cells. Large bowel histology showed protection from colitis in recipients of primed cells as indicated by normal colonic epithelium. In Balb/c mice, C. rodentium infection is followed by resistance, which can be transferred by CD4+ cells. Transfer of protection is associated with IL-17 secretion, enhanced serum IgG and faecal IgA secretion. This is the first study to demonstrate the mechanisms by which systemic resistance from previously C. rodentium-infected mice can be transferred to non-infected animals.

Proinflammatory impact of Staphylococcus epidermidis on the nasal epithelium quantified by IL-8 and GRO-alpha responses in primary human nasal epithelial cells.

BACKGROUND: Bacterial etiology of chronic rhinosinusitis (CRS) still remains controversial. Whereas Staphylococcus aureus enterotoxins have been detected in CRS, the impact of Staphylococcus epidermidis, a major commensal inhabitant of the nose, has not been studied. Among others, serine and cysteine proteases have been identified as factors of virulence in S. epidermidis. METHODS: S. epidermidis was examined in tissue biopsies of 30 CRS patients (16 with nasal polyposis) using standard procedures. Primary human nasal epithelial cells from inferior nasal turbinates (HNECs), from nasal polyps (NPECs) and A549 airway epithelial cells were stimulated with S. epidermidis supernatants DSM20044 or ATCC35984 and the IL-8 and GRO-alpha response was quantified by ELISA. Protease-triggered chemokine responses and involvement of NF-kappaB were investigated by addition of protease or NF-kappaB inhibitors. Activation of NF-kappaB was demonstrated by quantitative DNA binding assay. RESULTS: S. epidermidis was the most frequently isolated bacteria in the majority of CRS patients. HNECs and NPECs revealed no different IL-6 and IL-8 synthesis following stimulation with DSM20044 or ATCC35984. Stimulation of HNECs and A549 cells with S. epidermidis supernatants resulted in increased IL-8 and GRO-alpha expression which could be suppressed by the serine protease inhibitor AEBSF and the NF-kappaB inhibitor BAY 11 but not by the cysteine protease inhibitor E64. Results obtained for A549 cells were similar to HNECs. CONCLUSION: S. epidermidis was present in the majority of CRS specimens. Proinflammatory impact of S. epidermidis supernatants on nasal epithelial cells was demonstrated by serine protease-triggered and NF-kappaB-dependent chemokine responses.

Small-colony variants (SCVs) of staphylococci: a role in foreign body-associated infections.

Staphylococci have various strategies for resisting therapy that extend beyond classic mechanisms. Clinical experience with device-associated infections as well as with infections due to small-colony variants (SCVs) clearly shows that both antibacterial chemotherapy and host defense mechanisms are often unable to eliminate the pathogens and cure these infections. Of particular interest is the fact that in the past few years an increasing number of various foreign body-related infections due to staphylococcal SCVs have been reported. In this overview, the characteristics of SCVs recovered from clinical specimens and of defined mutants displaying the SCV phenotype are described. Their slow growth and changing biochemical and physiological features represent a challenge to clinical laboratory personnel, because recovery, identification, as well as susceptibility testing of these variants need particular efforts. In addition, the reduced susceptibility to aminoglycosides and the ability of SCVs to persist intracellularly require specific attention for the treatment of these infections. Thus, special efforts to search for these variants formed by Staphylococcus aureus or by coagulase-negative staphylococci should be considered when an infection is particularly resistant to therapy, persists for a long period or fails to respond to apparently adequate therapy with antimicrobial compounds.

Prevalence of genes encoding for staphylococcal leukocidal toxins among clinical isolates of Staphylococcus aureus from implant orthopedic infections.

Staphylococcus aureus has emerged as a major cause of implant infections. It is known that it is able to produce several toxins that contribute to its armory of virulent weapons, but there are still no data on their prevalence among isolates recovered from biomaterial-centered infections. In this study, 200 Staphylococcus aureus isolates from infections related to different types of orthopedic implants (hip and knee arthroprostheses, internal and external fixation devices) were tested by polymerase chain reaction for the prevalence of genes encoding for leukotoxins. Although almost all isolates were positive for the ã-hemolysin gene (99%), none was positive for lukM. The leukotoxin genes lukE/lukD were found in 67% of isolates. The presence of lukE/lukD was significantly associated with that of Accessory Gene Regulatory locus agr II. The lukE/lukD-positive isolates were significantly more prevalent in the staphylococcal isolates from knee arthroprostheses than in the isolates from the other implant types. The genes encoding Panton-Valentine leukocidin components were detected in only one isolate that, curiously enough, was taken solely from a knee arthroprosthesis infection.

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.

Modern strategies in the prevention of implant-associated infections.

The application of medical devices either for temporary or permanent use has become an indispensible part of almost all fields of medicine. However, foreign bodies are associated with a substantial risk of bacterial and fungal infections. Implant-associated infections significantly contribute to the still increasing problem of nosocomial infections. To reduce the incidence of such infections, specific guidelines providing evidence-based recommendations and comprising both technological and nontechnological strategies for prevention have been established. Strict adherence to hygienic rules during insertion or implantation of the device are aspects of particular importance. Besides such basic and indispensable aspects, the development of new materials which could withstand microbial adherence and colonization has become a major topic in recent years. Modification of surface by primarily physico-chemical methods may lead to a change in specific and unspecific interactions with microorganisms and, thus, to a reduction in microbial adherence. Medical devices made out of a material that would be ideally antiadhesive or at least colonization-resistant would be the most suitable candidates to avoid colonization and subsequent infection. However, it appears impossible to create a surface with an absolute 'zero'-adherence due to thermodynamical reasons and due to the fact that a modified material surface is in vivo rapidly covered by plasma and connective tissue proteins. Therefore, another concept for the prevention of implant-associated infections involves the impregnation of devices with various antimicrobial substances such as antibiotics, antiseptics, and/or metals. In fact, already commercially available materials for clinical use such as antimicrobial catheters have been introduced, in part with considerable impact on subsequent infections. However, future studies are warranted to translate the knowledge on the pathogenesis of device-associated infections into applicable prevention strategies.

Evaluation of an in situ setting injectable calcium phosphate as a new carrier material for gentamicin in the treatment of chronic osteomyelitis: studies in vitro and in vivo.

A study was performed to investigate the effectiveness of hydroxyapatite cement (HAC) as a new carrier system in the treatment of chronic, posttraumatic osteomyelitis. In the in vitro study, release of gentamicin from standard cylinders of HAC were measured by agar diffusion test. As a representative for mechanical properties, compression strength was measured in order to detect changes when mixing HAC with gentamicin. In the in vivo study, bone infection was induced according to the model of Norden by injection of 1 ml Na-morrhuat and 3 x 10(6)CFU Staphylococcus aureus. After 3 weeks, when chronic stage of infection was obtained, 17 animals were treated by debridement and filling the marrow either with HAC alone or HAC mixed with gentamicin (32 mg/g). Animals of the control groups were left untreated. After 6 weeks, all animals were sacrificed. Hematological, radiological, microbiological and histological examinations were carried out by covered investigation. Best evidence of the efficiency of treatment was observed in histopathological and microbiological findings. In all swabs of the control groups, taken 6 weeks following infection S. aureus were detected which were clonal to the strain used for induction of osteomyelitis. In HAC/gentamicin-treated animals, no growth was detectable after 7 days of culturing in BHI bouillon. In the HAC/gentamicin-treated group, there was no histopathological evidence of infection. In all other groups different stages of chronic osteomyelitis were found. No side effect was observed, neither locally nor systemically by HAC or gentamicin. Therefore, HAC is considered to be a very effective carrier for antibiotics in treatment of chronic, posttraumatic osteomyelitis.

Bactericidal effect of extracorporeal shock waves on Staphylococcus aureus.

Despite considerable knowledge about the effects of shock waves on eukaryotic soft tissues, no data are available concerning their effect on prokaryotic micro-organisms. In vitro studies on the bactericidal effect of extracorporeal shock waves on staphylococci were performed with energy levels that are standard for the disintegration of calculi. Suspensions containing 10(4)-10(5) cfu of Staphylococcus aureus/ml were sealed in plastic tubes and exposed to shock waves, resulting in a mean decrease of 3.1 log(10). Whereas impulse rates of > or =350 resulted in a decrease of cfu/ml equalling the detection limit, lower numbers of impulses did not result in an appreciable bactericidal effect. The bactericidal effect of extracorporeal shock waves might provide the basis for the development of novel therapeutic strategies for bacterial infections.

Hospital-acquired candida and aspergillus pneumonia--diagnostic approaches and clinical findings.

Bronchoscopy with bronchoalveolar lavage (BAL), collection of bronchial secretions (BS) and/or high resolution computed tomography (CT) of the lungs was performed in 70 patients with candida and/or aspergillus pneumonia. The sensitivity of bronchoscopy in detecting histologically proven fungal disease was 59%. Characteristic CT signs were found in 11 of 14 patients with candida pneumonia and 16 of 19 patients with aspergillosis. The more frequent use of bronchoscopy and CT scans between 1990 and 1992 compared with 1986-1989 for the differential diagnosis of new pulmonary infiltrates in immunocompromised patients resulted in earlier antifungal treatment (14 vs. nine days; P < 0 center dot 025). In the second treatment period survival was improved from 36 to 50% (not significant). Bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools and should be performed as early as possible in the course of pneumonia in patients at high risk of fungal diseases.

Coagulase-negative staphylococci. Pathogens have major role in nosocomial infections.

Coagulase-negative staphylococci live naturally on the skin and mucous membranes of humans and are therefore often found in clinical specimens. Distinguishing clinically significant, pathogenic strains from contaminant strains is one of the major challenges facing clinical microbiology laboratories. S epidermidis and other novobiocin-susceptible coagulase-negative staphylococci have emerged as a major cause of nosocomial infections, particularly of nosocomial bacteremia in immunocompromised patients. S epidermidis also is common in injecting drug users, who are particularly susceptible to right-sided endocarditis, and--most important--in patients with such indwelling foreign bodies as intravenous catheters. Depending on the kind of device and its insertion site, different infection syndromes generate a variety of clinical presentations. In these patients, the host defense mechanisms often seem unable to handle the infection and, in particular, to eliminate the staphylococci from the infected device because of a biofilm on the foreign body surface. S saprophyticus, the most commonly isolated bacterium of the novobiocin-resistant coagulase-negative staphylococci, is a common pathogen of the urogenital tract; it generally infects immunocompetent patients, particularly young, sexually active men and women.

Staphylococcus aureus small colony variants: formation and clinical impact.

S. aureus small-colony variants are a naturally occurring subpopulation which grow slowly and produce small colonies on routine media. They also demonstrate a number of other characteristics that are atypical for S. aureus including reduced alpha-toxin production and delayed coagulase activity. The connection of S. aureus SCVs with persistent and relapsing infections has been defined over the past decade, especially in patients with chronic osteomyelitis and in cystic fibrosis patients as demonstrated by prospective studies. While the studies with clinical isolates of SCVs suggested a link between electron transport-defective strains and persistent infections, a defined hemB mutant with the SCV phenotype provided strong additional evidence for these connections. The hemB mutant was phagocytosed by cultured endothelial cells, but did not lyse these cells, because the mutant produced very little alpha-toxin. The intracellular location may shield the SCVs from host defenses and antibiotics, thus providing one explanation for the difficulty in clearing S. aureus SCVs from host tissues.

Trends in antimicrobial non-susceptibility in methicillin-resistant Staphylococcus aureus from Germany (2004-2011).

We analysed trends in antimicrobial non-susceptibility in methicillin-resistant Staphylococcus aureus (MSRA) from Germany to assess the impact of the changing population structure of MRSA on antimicrobial resistance rates. During two large nationwide multicentre studies in 2004-2005 and 2010-2011, we collected consecutively spa-genotyped MRSA isolates. The increase in non-susceptibility rates for tetracycline and trimethoprim-sulphamethoxazole was associated with the spread of livestock-associated MRSA. A decrease in non-susceptibility rates for aminoglycosides and quinolones affected all major lineages (spa-clonal complexes 003, 008, and 032). All isolated remained susceptible to glycopeptides and linezolid.