Christof von Eiff

Nasal Carriage as a Source of Staphylococcus aureus Bacteremia

BACKGROUND The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patients own flora. METHODS In a multicenter study, swabs for culture were obtained from the anterior nares of 219 patients with S. aureus bacteremia. A total of 723 isolates were collected and genotyped. In a second study, 1640 S. aureus isolates from nasal swabs were collected over a period of five years and then compared with isolates from the blood of patients who subsequently had S. aureus bacteremia. RESULTS In the multicenter study of S. aureus bacteremia, the blood isolates were identical to those from the anterior nares in 180 of 219 patients (82.2 percent). In the second study, 14 of 1278 patients who had nasal colonization with S. aureus subsequently had S. aureus bacteremia. In 12 of these 14 patients (86 percent), the isolates obtained from the nares were clonally identical to the isolates obtained from blood 1 day to 14 months later. CONCLUSIONS A substantial proportion of cases of S. aureus bacteremia appear to be of endogenous origin since they originate from colonies in the nasal mucosa. These results provide support for strategies to prevent systemic S. aureus infections by eliminating nasal carriage of S. aureus.

Pathogenesis of infections due to coagulasenegative staphylococci

As a group, the coagulase-negative staphylococci (CoNS) are among the most frequently isolated bacteria in the clinical microbiology laboratory and are becoming increasingly important, especially as causes of hospital-acquired infections. These bacteria are normal inhabitants of human skin and mucous membranes and, therefore, one of the major challenges of daily diagnostic work is to distinguish clinically significant CoNS from contaminant strains. This overview addresses current knowledge of the pathogenesis of infections due to CoNS and particularly focuses on virulence factors of the species Staphylococcus epidermidis. S epidermidis has been identified as a major cause of nosocomial infections, especially in patients with predisposing factors such as indwelling or implanted foreign polymer bodies. Most important in the pathogenesis of foreign-body-associated infections is the ability of these bacteria to colonise the polymer surface by the formation of a thick, multilayered biofilm. Biofilm formation takes place in two phases. The first phase involves the attachment of the bacteria to polymer surfaces that may be either unmodified or coated with host extracellular matrix proteins. In the second phase, the bacteria proliferate and accumulate into multilayered cell clusters that are embedded in an extracellular material. The bacterial factors involved in both phases of biofilm formation are discussed in this review. In addition, the most important aspects of the pathogenic potential of S saprophyticus, S lugdunensis, and S schleiferi are described, although, compared with S epidermidis, much less is known in these species concerning their virulence factors.

Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections.

Small colony variants constitute a slow-growing subpopulation of bacteria with distinctive phenotypic and pathogenic traits. Phenotypically, small colony variants have a slow growth rate, atypical colony morphology and unusual biochemical characteristics, making them a challenge for clinical microbiologists to identify. Clinically, small colony variants are better able to persist in mammalian cells and are less susceptible to antibiotics than their wild-type counterparts, and can cause latent or recurrent infections on emergence from the protective environment of the host cell. This Review covers the phenotypic, genetic and clinical picture associated with small colony variants, with an emphasis on staphylococci, for which the greatest amount of information is available.

Infections Associated with Medical Devices Pathogenesis, Management and Prophylaxis

The insertion or implantation of foreign bodies has become an indispensable part in almost all fields of medicine. However, medical devices are associated with a definitive risk of bacterial and fungal infections. Foreign body-related infections (FBRIs), particularly catheter-related infections, significantly contribute to the increasing problem of nosocomial infections. While a variety of microorganisms may be involved as pathogens, staphylococci account for the majority of FBRIs. Their ability to adhere to materials and to promote formation of a biofilm is the most important feature of their pathogenicity. This biofilm on the surface of colonised foreign bodies is regarded as the biological correlative for the clinical experience with FBRI, that is, that the host defence mechanisms often seem to be unable to handle the infection and, in particular, to eliminate the microorganisms from the infected device. Since antibacterial chemotherapy is also frequently not able to cure these infections despite the use of antibacterials with proven in vitro activity, removal of implanted devices is often inevitable and has been standard clinical practice. However, in specific circumstances, such as infections of implanted medical devices with coagulase-negative staphylococci, a trial of salvage of the device may be justified. All FBRIs should be treated with antibacterials to which the pathogens have been shown to be susceptible. In addition to systemic antibacterial therapy, an intraluminal application of antibacterial agents, referred to as the ‘antibiotic-lock’ technique, should be considered to circumvent the need for removal, especially in patients with implanted long-term catheters.To reduce the incidence of intravascular catheter-related bloodstream infections, specific guidelines comprising both technological and nontechnological strategies for prevention have been established. Quality assurance, continuing education, choice of the catheter insertion site, hand hygiene and aseptic techniques are aspects of particular interest. Furthermore, all steps in the pathogenesis of biofilm formation may represent targets against which prevention strategies may be directed. Alteration of the foreign body material surface may lead to a change in specific and nonspecific interactions with micro-organisms and, thus, to a reduced microbial adherence. Medical devices made out of a material that would be antiadhesive or at least colonisation resistant would be the most suitable candidates to avoid colonisation and subsequent infection. Another concept for the prevention of FBRIs involves the impregnation of devices with various substances such as antibacterials, antiseptics and/or metals. Finally, further studies are needed to translate the knowledge on the mechanisms of biofilm formation into applicable therapeutic and preventive strategies.

Prevalence of Genes Encoding Pyrogenic Toxin Superantigens and Exfoliative Toxins among Strains of Staphylococcus aureus Isolated from Blood and Nasal Specimens

ABSTRACT A total of 429 different Staphylococcus aureus isolates encompassing 219 blood isolates and 210 isolates taken from anterior nares were systematically searched by two multiplex PCR-DNA enzyme immunoassays (PCR-DEIA) for exfoliative toxin (ET) genes eta and etb, as well as for the classical members of the pyrogenic toxin superantigen (PTSAg) gene family comprising the staphylococcal enterotoxin (SE) genes sea-see and the toxic shock syndrome toxin 1 gene tst. In addition, a third PCR-DEIA was established to investigate the possession of four recently described SE genes, viz. seg-sej. The most frequent PTSAg/ET genes amplified were seg and sei, which were found strictly in combination in 55.0% of the S. aureus isolates tested. Other frequently detected toxin genes were tst (20.3%), sea (15.9%), and sec (11.2%). Only five isolates harbored ET genes. Regarding the origin of the S. aureus isolates, a significant difference (P = 0.037) was found for the possession of the sed/sej gene combination (10.5% of blood isolates versus 3.3% of nasal strains). Overall, about half of S. aureus isolates tested harbored genes of the classical members of the PTSAg family and ETs (50.8%), whereas 73.0% of S. aureus isolates were toxin gene positive if the recently described SE genes were included. This notable higher prevalence indicates that the possession of PTSAg genes in particular seems to be a habitual feature of S. aureus. Moreover, mainly due to the fixed combinations of seg plus sei, as well as sed plus sej, the possession of multiple PTSAg genes (62.9%) is more frequent than assumed so far.

Staphylococcal Small Colony Variants Have Novel Mechanisms for Antibiotic Resistance

Over the past 4 years, a variant subpopulation of Staphylococcus aureus has been characterized that is defective in electron transport. These organisms grow slowly and are typical of the previously described small colony variants (SCVs). Indeed, many earlier papers included data that are consistent with defective respiratory activity in SCVs. We present a hypothesis that serves as biochemical basis for the development of SCVs. These variants are particularly interesting because they have been associated with very persistent infections, and they are more resistant to many antibiotics than normal S. aureus. Because of their slow growth, atypical colonial morphology, and unusual biochemical profile, they are easily missed or misidentified in the clinical laboratory. This is of some significance, as this subpopulation is more resistant to antibiotics than the parent population from which they arose. When an infection is particularly resistant to therapy, persists for a long period, or fails to respond to apparently adequate antimicrobial therapy, clinicians and clinical laboratory personnel should consider special efforts to search for SCVs.

Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma.

The placement of megaprostheses in patients with bone sarcoma is associated with high rates of infection, despite prophylactic antibiotic administration. In individual cases, secondary amputation is unavoidable in the effort to cure infection.

Intracellular Persistence of Staphylococcus aureus Small-Colony Variants within Keratinocytes: A Cause for Antibiotic Treatment Failure in a Patient with Darier's Disease

Intracellular persistence assays were performed with small-colony variants (SCVs) derived from a patient with Dariers disease from whom different phenotypes and genotypes of Staphylococcus aureus were isolated over a 28-month period; the assays revealed that >100-fold more SCV cells persisted intracellularly relative to the normal phenotype. The presence of intracellular S. aureus SCVs may protect against host defenses and antibiotic therapy and thus may have contributed to this patients very prolonged skin infection.

Increased Expression of Clumping Factor and Fibronectin-Binding Proteins by hemB Mutants of Staphylococcus aureus Expressing Small Colony Variant Phenotypes

ABSTRACT Small colony variants (SCVs) of Staphylococcus aureus are slow-growing subpopulations that cause persistent and relapsing infections. The altered phenotype of SCV can arise from defects in menadione or hemin biosynthesis, which disrupt the electron transport chain and decrease ATP concentrations. With SCVs, virulence is altered by a decrease in exotoxin production and susceptibility to various antibiotics, allowing their intracellular survival. The expression of bacterial adhesins by SCVs is poorly documented. We tested fibrinogen- and fibronectin-mediated adhesion of a hemB mutant of S. aureus 8325-4 that is defective for hemin biosynthesis and exhibits a complete SCV phenotype. In this strain, adhesion to fibrinogen and fibronectin was significantly higher than that of its isogenic, normally growing parent and correlated with the increased surface display of these adhesins as assessed by flow cytometry. Real-time quantitative reverse transcription-PCR demonstrated increased expression of clfA and fnb genes by the hemB mutant compared to its isogenic parent. The influence of the hemB mutation on altered adhesin expression was confirmed by showing complete restoration of the wild-type adhesive phenotype in the hemB mutant, either by complementing with intact hemB or by supplementing the growth medium with hemin. Increased surface display of fibrinogen and fibronectin adhesins by the hemB mutation occurred independently from agr, a major regulatory locus of virulence factors in S. aureus. Both agr-positive and agr-lacking hemB mutants were also more efficiently internalized by human embryonic kidney cells than were their isogenic controls, presumably because of increased surface display of their fibronectin adhesins.

Left ventricular assist device infection is associated with increased mortality but is not a contraindication to transplantation.

BACKGROUND Left ventricular assist devices (LVADs) are increasingly used as a bridge to transplantation. Infection is a frequent and major complication associated with the use of these devices, however, the correlation of infection and outcome has not yet been evaluated in a prospective fashion. METHODS AND RESULTS Twenty-five patients (24 male, 1 female) with end-stage cardiac failure and resulting organ dysfunction were included. Patients were bridged with the Novacor N100 portable LVAD (median duration of support, 55 days) and were evaluated prospectively by device surface cultures on explantation, molecular typing of isolates, and correlation of infection with survival to transplant. Twelve (48%) of 25 patients had LVAD infection as defined by recovery of multiple isolates of identical genotype from the device surface. Whereas only 5 (42%) of 12 patients with LVAD infection survived until transplantation, 11 (85%) of 13 patients without infection were successfully transplanted (P < .05). Death of the 7 patients with proven LVAD infection was associated with multiple organ failure or other signs of acute infection. CONCLUSIONS LVAD infection is associated with a significantly decreased survival probability. It does not preclude successful bridging but rather may pose an indication for urgent transplantation.