Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.

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Bacterial biofilms: from the natural environment to infectious diseases.

Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until 1978. We now understand that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health. Using tools such as the scanning electron microscope and, more recently, the confocal laser scanning microscope, biofilm researchers now understand that biofilms are not unstructured, homogeneous deposits of cells and accumulated slime, but complex communities of surface-associated cells enclosed in a polymer matrix containing open water channels. Further studies have shown that the biofilm phenotype can be described in terms of the genes expressed by biofilm-associated cells. Microorganisms growing in a biofilm are highly resistant to antimicrobial agents by one or more mechanisms. Biofilm-associated microorganisms have been shown to be associated with several human diseases, such as native valve endocarditis and cystic fibrosis, and to colonize a wide variety of medical devices. Though epidemiologic evidence points to biofilms as a source of several infectious diseases, the exact mechanisms by which biofilm-associated microorganisms elicit disease are poorly understood. Detachment of cells or cell aggregates, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are all biofilm processes which could initiate the disease process. Effective strategies to prevent or control biofilms on medical devices must take into consideration the unique and tenacious nature of biofilms. Current intervention strategies are designed to prevent initial device colonization, minimize microbial cell attachment to the device, penetrate the biofilm matrix and kill the associated cells, or remove the device from the patient. In the future, treatments may be based on inhibition of genes involved in cell attachment and biofilm formation.

Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms

Micrococcus, which, when limited in its extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicaemia and pyaemia.1 In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.1,2 More than 100 years later, Staphylococcus aureus remains a versatile and dangerous pathogen in humans. The frequencies of both community-acquired and hospital-acquired staphylococcal infections have increased steadily, with little change in overall mortality. Treatment of these infections . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199808203390806?articleTools=true

Staphylococcus aureus infections.

Silver nanoparticles as a new generation of antimicrobials.

Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease Key Laboratory Features of NTM Health Careand Hygiene-associated Disease Prevention Prophylaxis and Treatment of NTM Disease Introduction Methods Taxonomy Epidemiology Pathogenesis Host Defense and Immune Defects Pulmonary Disease Body Morphotype Tumor Necrosis Factor Inhibition Laboratory Procedures Collection, Digestion, Decontamination, and Staining of Specimens Respiratory Specimens Body Fluids, Abscesses, and Tissues Blood Specimen Processing Smear Microscopy Culture Techniques Incubation of NTM Cultures NTM Identification Antimicrobial Susceptibility Testing for NTM Molecular Typing Methods of NTM Clinical Presentations and Diagnostic Criteria Pulmonary Disease Cystic Fibrosis Hypersensitivity-like Disease Transplant Recipients Disseminated Disease Lymphatic Disease Skin, Soft Tissue, and Bone Disease

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An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases.

About half of all nosocomial infections are associated with indwelling devices. Infections associated with implanted surgical devices are particularly difficult to deal with because they can require prolonged antibiotic treatment and repeated surgical procedures. This review summarizes the diagnostic challenges and explains the approaches to managing infections that are associated with various devices, including prosthetic heart valves, vascular grafts, pacemakers and defibrillators, and joint prostheses.

https://www.nejm.org/doi/pdf/10.1056/NEJMra035415?listPDF=true

Treatment of infections associated with surgical implants.

BACKGROUND Since the patient’s skin is a major source of pathogens that cause surgical-site infection, optimization of preoperative skin antisepsis may decrease postoperative infections. We hypothesized that preoperative skin cleansing with chlorhexidine–alcohol is more protective against infection than is povidone–iodine. METHODS We randomly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine–alcohol scrub or povidone–iodine scrub and paint. The primary outcome was any surgical-site infection within 30 days after surgery. Secondary outcomes included individual types of surgical-site infections. RESULTS A total of 849 subjects (409 in the chlorhexidine–alcohol group and 440 in the povidone–iodine group) qualified for the intention-to-treat analysis. The overall rate of surgical-site infection was significantly lower in the chlorhexidine–alcohol group than in the povidone–iodine group (9.5% vs. 16.1%; P = 0.004; relative risk, 0.59; 95% confidence interval, 0.41 to 0.85). Chlorhexidine–alcohol was significantly more protective than povidone–iodine against both superficial incisional infections (4.2% vs. 8.6%, P = 0.008) and deep incisional infections (1% vs. 3%, P = 0.05) but not against organ-space infections (4.4% vs. 4.5%). Similar results were observed in the per-protocol analysis of the 813 patients who remained in the study during the 30-day follow-up period. Adverse events were similar in the two study groups. CONCLUSIONS Preoperative cleansing of the patient’s skin with chlorhexidine–alcohol is superior to cleansing with povidone–iodine for preventing surgical-site infection after cleancontaminated surgery. (ClinicalTrials.gov number, NCT00290290.)

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Chlorhexidine–Alcohol versus Povidone–Iodine for Surgical-Site Antisepsis

The number of indwelling medical devices is escalating, and an increasing proportion of device-related infections are being caused by Candida spp. Candida spp. produce biofilms on synthetic materials, which facilitates adhesion of the organisms to devices and renders them relatively refractory to medical therapy. Management of device-related Candida infections can be challenging. Removal of the infected device is generally needed to establish cure of Candida infections of medical devices. However, since the pathogenesis of Candida bloodstream infection is complicated, more studies are necessary to determine the role of catheter exchange in patients with both gastrointestinal tract mucositis and indwelling catheters. The medical and economic impact of these infections is enormous.

Candida Infections of Medical Devices

Background The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. Methods We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199901073400101

A comparison of two antimicrobial-impregnated central venous catheters

Medical devices are responsible for a large portion of nosocomial infections, particularly in critically ill patients. Deviceassociated infections can cause major medical and economic sequelae. Bacterial colonization of the indwelling device can be a prelude to both infection and malfunction of the device. The pathogenesis of device-associated infection centers around the multifaceted interaction among the bacteria, the device, and the host. Bacterial factors are probably the most important in pathogenesis of infection, whereas device factors are the most amenable to modification with the objective of preventing infection. Some, but not all, of the studied bacterial receptors satisfy the proposed “adherence/infection” version of Koch’s postulates. Traditional surface-modifying preventive approaches have largely focused on antimicrobial coating of devices and resulted in variable clinical success in preventing device-associated infections. The potential protective role of newer innovative approaches, such as biofilm modification and bacterial interference, ought to be further investigated. American medicine has made great strides during the past several years, owing to enhanced medical knowledge and advanced technology. The more extensive use of medical devices has affected mostly critically ill patients, which has resulted in longer survival of patients who are at even higher risk for infection. Most cases of infection in critically ill patients are associated with medical devices. In this population of patients, 95% of cases of urinary tract infection are catheter related, 87% of cases of bloodstream infection originate from an indwelling vascular catheter, and 86% of cases of pneumonia are associated with mechanical ventilation [1]. The objectives of this article are to (1) assess the magnitude of the general problem of device-associated infections; (2) ad

Rabih O. Darouiche

Papers

Treatment of infections associated with surgical implants.

Chlorhexidine–Alcohol versus Povidone–Iodine for Surgical-Site Antisepsis

Candida Infections of Medical Devices

A comparison of two antimicrobial-impregnated central venous catheters

Device-associated infections: a macroproblem that starts with microadherence.