Infections Associated with Indwelling Medical Devices, Third Edition

This chapter focuses on the fibronectin-binding proteins (FnBPs) and fibrinogen-binding proteins (clumping factors, Clf) of Staphylococcus aureus. The role of the proteins in promoting bacterial adherence to immobilized ligand has been defined using site-specific adhesin-defective mutants that are compared with the parental strains in in vitro and in vivo models of foreign-body infection. The fnbA and fnbB genes of the laboratory strain 8325-4 have been inactivated by allelic replacement. This fnbAfhbB double mutant and the mutant carrying a multicopy plasmid that causes overexpression of FnBPA have allowed the role of FnBPs in promoting bacterial interactions with fibronectin to be defined. The fnbAfnbB mutant of strain 8325-4 was also defective in adherence to coverslips removed from subcutaneous chambers implanted in guinea pigs. The growth conditions used to prepare the bacterial cells for the adherence and virulence experiments would have prevented expression of the second clumping factor ClfB. The ClfA- mutant was defective in adherence to immobilized fibrinogen, while the complemented mutant adhered as well as the wild-type. The increasing incidence of multiple-antibiotic-resistant strains causing nosocomial infections has increased the urgency for alternative approaches to prevention and therapy. The problem is compounded by the recent emergence of methicillin-resistant S. aureus (MRSA) with intermediate sensitivity to vancomycin. In conclusion, there are several experimental vaccines that provide clear protection against S. aureus infections in animals. The challenge is to determine if any of these will protect human patients against nosocomial disease and, in particular, biomaterial-related infection.

In 1981, intravenous catheters infected with staphylococci by perfusion were investigated by scanning electron microscopy (SEM) to demonstrate the mode of adhesion. Bacterial cells, primarily those of staphylococci, followed by Acinetobacter calcoaceticus and Pseudomonas aeruginosa, were shown to be attached to the inner surface of the catheter. The thickest bacterial layers were found in catheters infected by coagulase-negative staphylococci (CoNS). Right heart flow-directed catheters removed from 18 critically ill patients after an average of 2.6 days after insertion were covered by a bacterial biofilm. In a neonatal intensive care unit, CoNS caused the majority of the nosocomial bacteremias. A study of arterial and central venous catheters removed from patients after 1 to 14 days revealed an extensive biofilm on all 42 arterial and 26 central venous catheters. By using special biofilm culture recovery methods, it was shown that 81% of the catheters were colonized by bacteria growing in slime-enclosed biofilms. It was speculated that the colonization represents a nidus for infection and bacteremia in these patients. Staphylococci also produced biofilm on polyvinyl chloride (PVC) endotracheal tubes used in neonates. Adherence of staphylococci to various intravascular catheter materials was investigated; these materials were composed of silicone elastomer, thermoplastic polyurethane, and polyurethane coated with Hydromer, a coating that absorbs water and provides a hydrophilic sheath around the catheter. Production of slime is necessary for Staphylococcus epidermidis colonization and is also observed with many other pathogens, including S. aureus.

The pathogenesis of vascular catheter infections has recently been extensively reviewed. This chapter summarizes existing understandings and presents details of new work published on vascular catheter infections since the recent reviews. Many factors have been shown to affect the risk of catheters becoming infected. These include the unique abilities of certain organisms, Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans, to cause catheter-related infections. Molecular typing studies increasingly are improving our understanding of the pathogenesis of S. epidermidis/CoNS catheter-related infection. Recent studies with isogenic S. epidermidis mutants increasingly suggest that production of a polysaccharide adhesin is crucial to the pathogenesis of foreign-body infection. This polysaccharide, first named PS/A, was initially described as a virulence factor in association with work examining the pathogenesis of endocarditis. Two additional findings of relevance to the pathogenesis of endocarditis and possibly vascular catheter infections are that binding to platelets facilitates endocarditis and S. aureus strains causing endocarditis are much more likely to be resistant to platelet microbicidal proteins. The pathogenesis of catheter-related thrombosis has been studied in greater depth in recent years. With peripheral catheters, ultrasonographic imaging has shown that early thrombus formation (<24 h after insertion) occurs near the site of insertion, whereas later thrombus formation (>24 h after insertion) occurs near the catheter tip. Recent in vitro studies have shown that surface manipulations of polyurethane can lead to differences in protein and platelet deposition with associated differences in bacterial adherence.

Prosthetic valve endocarditis (PVE) occurs in 1 to 9.4% of valve recipients. The PVE studies that were reviewed often lacked comprehensive follow-up information on operated patients and thus may have failed to account for infections that were not treated at the reporting institution. Calderwood et al. found 116 patients with PVE in 2,608 patients that survived valve replacement surgery done from January 1975 through December 1982. Actuarial estimates of cumulative risks in this study were 3.1% at 12 months and 5.7% at 60 months. The increasing incidence of PVE on bioprosthetic valves with time elapsed after the initial postoperative year, combined with the leaflet localization of those late onset infections, suggests that anatomic changes in bioprosthetic valve leaflets over time may increase the susceptibility of these valves to endocarditis. Suspecting that the pathogenesis of some infections would relate to nosocomial events, particularly those occurring during or shortly after surgery, Block et al. coined the term “early PVE” for patients with onset of infection within 60 days of surgery. Cefamandole was more effective than cefazolin in preventing wound infections, particularly those caused by Staphylococcus aureus, in cardiac surgery patients. In one randomized double-blind trial, patients undergoing cardiac or major vascular surgery who received vancomycin experienced fewer surgical wound infections than did those who received cefazolin or cefamandole. However, in this study there was no significant difference in surgical wound infection rates between recipients of the various prophylactic antibiotic regimens when one considered patients undergoing cardiac surgery.

This chapter talks about a new diagnostic and therapeutic approach based on the ambulatory management of infections to minimize the social consequences for the patient and the important economic impact for the community. Coagulase-negative staphylococci, streptococci, gram-negative aerobes, and anaerobes are the most common bacteria in late-onset prosthetic joint infections. Infections within the first few months of surgery usually present with pain, erythema, and drainage at the wound site. The combination of fleroxacin with rifampin resulted in a 41% cure rate in an Staphylococcus aureus foreign-body infection model. The addition of vancomycin to the fleroxacin-rifampin combination significantly increased the cure rate and the rapidity of sterilization of the foreign body. Fusidic acid can accumulate within cells, demonstrated by the fact that 7- to 10-fold intracellular compared with extracellular concentrations have been measured in human polymorphonuclear leukocytes and lymphocytes. The only antibiotics remaining active against multiresistant staphylococci and able to diffuse into the bone tissue are glycopeptides (vancomycin and teicoplanin) and co-trimoxazole. Bone marrow changes occur in patients with preexisting depleted folate stores and one recent report established that bone marrow changes occur in one case per 18,000 prescriptions. Ciprofloxacin has an excellent penetration into bone and an excellent MIC for Pseudomonas aeruginosa. Ciprofloxacin alone is effective in the treatment of P. aeruginosa osteomyelitis. Salvage of infected orthopedic implants by appropriate antimicrobial strategies is feasible and the ambulatory management of such infections contributes to humanization of therapy.

This chapter discusses infections related to pacemakers (PMs) or implantable cardioverter defibrillators (ICDs) are major complications and are difficult to manage; complete removal of the device is required in a majority of cases. Many factors such as diabetes, underlying malignancy, corticosteroids, anticoagulation, and advanced age have been suspected as potential predisposing factors for developing a device-related infection, but only some of them can nowadays be considered as well characterized independent risk factors. The diagnosis of a device-related infection can be difficult to establish. The clinical presentation depends on many variables, including the site of infection (the pulse-generator pocket and/or the conducting system), the type of electrode implanted (epicardial or intraventricular transvenous), the route of contamination (erosion, wound or pocket infection, secondary to a bacteremia, or contiguous spread from an adjacent infectious focus), and the microorganism involved. In summary, the diagnosis of an implanted device-related infection must be suspected in the presence of any erosion of an implanted device, chronic fever without documented infectious foci, multiple pulmonary infiltrates or emboli, and/or persistent or relapsing evidence of infection at the insertion site. Despite strong microbiological and epidemiological data suggesting that local contamination with the flora present in the skin appendages might contaminate the wound margin during the surgical procedure and be responsible for a majority of device-related infections, systemic antibiotic prophylaxis has remained controversial. Almost all authors report the necessity for assiduous skin disinfection before surgery, and others employ intrapocket antibiotic spray or instillation before insertion.

Ocular infections attributed to foreign bodies may be categorized by the anatomic location of the infection. This chapter concentrates on microbial keratitis secondary to contact-lens use and endophthalmitis after surgical or traumatic perforation of the eye. Foreign-body-associated lid and orbit infections are mainly secondary to trauma. The diameter and configuration of the infection, its relationship to the visual axis, its depth in the cornea, and the presence of associated eye conditions should be noted, and if possible, photography should be performed. Corneal scrapings for cultures are required for precise microbiologic diagnosis. The overwhelming risk factor for microbial keratitis among lens wearers is overnight wear. Given current contact-lens technology, the most effective way to reduce the incidence of infections is to discourage overnight wear of lenses. Any contact-lens-wearing subject who experiences the acute onset of ocular pain, decreased vision, and a red eye should remove the lens and seek ophthalmologic attention promptly. As opposed to infections in contact with a prosthesis elsewhere in the body that usually require removal of the prosthesis for sterilization, in cases of acute endophthalmitis following cataract surgery there is no evidence to support the notion that the intraocular lens (IOL) should be removed. Oral fluconazole (800 mg or more) may be efficacious as a long-term follow-up antibiotic for Candida endophthalmitis. Some surgeons add antibiotic (e.g., vancomycin) to the intraocular injected solutions used during cataract surgery.

Outside of the urinary tract, foreign bodies that are implanted (such as pacemakers, central nervous system shunts, heart valves, and joints) usually remain uninfected. Urinary tract infection is the most common nosocomial infection in the United States, and the vast majority of such cases are the result of bladder catheterization. Other less common foreign-body infections in the urinary tract involve prosthetic devices such as stents, bladder sphincters, and penile implants. The diagnosis of catheter-related urinary tract infection is based on both clinical and laboratory information. Bladder catheterization is by far the most common situation in which infection associated with a foreign body occurs in the urinary tract. Complications of bladder catheterization are relatively frequent and may be serious. Urinary tract stones are a common problem in patients with chronic indwelling catheters and may occur in part as a result of chronic or repeated infections with urease-splitting organisms such as Proteus species. The frequency of symptomatic urinary tract infections in patients with ureteral stents varies greatly.

In the beginning, the clinical evaluation of osscointegrated implants comprised primarily edentulous patients, suffering mostly from advanced atrophy of the osseous alveolar ridge as a consequence of tooth loss. During the last decade, the clinical use of osseointegrated dental implants has also been extended to partially dentate patients, addressing distally shortened dental arches and extended edentulous gaps, as well as single missing teeth, involving both the maxilla and the mandible. Single-tooth replacement with dental implants has recently become an increasingly applied treatment option, even in the esthetically sensitive anterior maxilla, and the few prospective studies available to date have reported favorable results. A recent study reported that out of 1,352 placed implants, 1,147 concerned partially dentate patients. As they are widely used in sites of limited bone height but high levels of occlusal load, distinctly increased requirements comprising both quality of osseointegration and biomechanical properties of the fixture-abutment complex itself are currently associated with dental implants. Osseointegrated dental implants or their secondary prosthetic components are in direct contact with the complex oral ecosystem, comprising fluids and high concentrations of various microbiota. Depending on the respective continuing diagnosis during the maintenance phase, developing peri-implant lesions should be intercepted as early as possible and treated according to the principles of the cumulative interceptive supportive therapy (CIST) protocols. Promising reports related to novel preventive and therapeutic approaches and concepts, including regenerative procedures and tissue engineering, indicate that dental implant therapy will continue to evolve as a highly effective and predictable treatment modality.

Millions of intravascular catheters are purchased each year by hospitals and clinics, placing many patients at risk for serious catheter-related infections. This chapter summarizes the rapidly expanding body of literature concerning prevention of intravascular catheter-related infections in the hope of reducing the risk posed to present and future patients. Prophylaxis with vancomycin or teicoplanin during central venous catheter insertion does not reduce the incidence of catheter-related bloodstream infection. The addition of prophylactic vancomycin to flush solutions or total parenteral nutrition solutions significantly reduces the incidence of catheter-related bloodstream infection; however, use of systemic antimicrobial agents to prevent intravascular catheter-related infections is not recommended. Administering very low doses of warfarin reduces thrombosis due to long-term central venous catheters. Use of prophylactic heparin by bolus infusion or when it is added to intravenous solutions does not significantly reduce the risk of central venous catheter-related bloodstream infection. Prophylactic heparin significantly reduces the incidence of catheter-related central venous thrombosis in patients with central venous and pulmonary artery catheters. A number of different strategies can be used to prevent serious intravascular catheter-related infections.