The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs.

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Antibacterial resistance worldwide: causes, challenges and responses.

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the numbers of and mortality rates for patients with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteremia. Data were extracted on demographic characteristics of the patients, adjustment for severity and comorbid illness, source of bacteremia, and crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality. When the results were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia was evident (OR, 1.93; 95% CI, 1.54-2.42; P<.001); significant heterogeneity was present. We explored the reasons for heterogeneity by means of subgroup analyses. MRSA bacteremia is associated with significantly higher mortality rate than is MSSA bacteremia.

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Comparison of mortality associated with methicillin-resistant and methicillin-susceptible staphylococcus aureus bacteremia: A meta-analysis

Summary: Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.

Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic.

OBJECTIVE: To better understand the absolute and relative risks of bloodstream infection (BSI) associated with the various types of intravascular devices (IVDs), we analyzed 200 published studies of adults in which every device in the study population was prospectively evaluated for evidence of associated infection and microbiologically based criteria were used to define IVD-related BSI. METHODS: English-language reports of prospective studies of adults published between January 1, 1966, and July 1, 2005, were identified by MEDLINE search using the following general search strategy: bacteremia [Medical Subject Heading, MeSH] OR septicemia [MeSH] OR bloodstream infection AND the specific type of intravascular device (eg, central venous port). Mean rates of IVDrelated BSI were calculated from pooled data for each type of device and expressed as BSIs per 100 IVDs (%) and per 1000 IVD days. RESULTS: Point incidence rates of IVD-related BSI were lowest with peripheral intravenous catheters (0.1%, 0.5 per 1000 IVDdays) and midline catheters (0.4%, 0.2 per 1000 catheter-days). Far higher rates were seen with short-term noncuffed and nonmedicated central venous catheters (CVCs) (4.4%, 2.7 per 1000 catheter-days). Arterial catheters used for hemodynamic monitoring (0.8%, 1.7 per 1000 catheter-days) and peripherally inserted central catheters used in hospitalized patients (2.4%, 2.1 per 1000 catheter-days) posed risks approaching those seen with short-term conventional CVCs used in the intensive care unit. Surgically implanted long-term central venous devices—cuffed and tunneled catheters (22.5%, 1.6 per 1000 IVD-days) and central venous ports (3.6%, 0.1 per 1000 IVD-days)—appear to have high rates of infection when risk is expressed as BSIs per 100 IVDs but actually pose much lower risk when rates are expressed per 1000 IVD-days. The use of cuffed and tunneled dual lumen CVCs rather than noncuffed, nontunneled catheters for temporary hemodialysis and novel preventive technologies, such as CVCs with anti-infective surfaces, was associated with considerably lower rates of catheter-related BSI. CONCLUSIONS: Expressing risk of IVD-related BSI per 1000 IVDdays rather than BSIs per 100 IVDs allows for more meaningful estimates of risk. These data, based on prospective studies in which every IVD in the study cohort was analyzed for evidence of infection by microbiologically based criteria, show that all types of IVDs pose a risk of IVD-related BSI and can be used for benchmarking rates of infection caused by the various types of IVDs in use at the present time. Since almost all the national effort and progress to date to reduce the risk of IVD-related infection have focused on short-term noncuffed CVCs used in intensive care units, infection control programs must now strive to consistently apply essential control measures and preventive technologies with all types of IVDs.

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The Risk of Bloodstream Infection in Adults With Different Intravascular Devices: A Systematic Review of 200 Published Prospective Studies

Ten patients with bacteremia due to methicillin-resistant Staphylococcus aureus were treated with vancomycin. These patients were compared with matched controls, nine bacteremic patients with methicillin-sensitive S. aureus, and one patient with penicillin-sensitive S. aureus. Controls were treated with a penicillin. There were no significant differences in time to defervescence, metastatic infections, relapse, mortality, need for surgical drainage, or duration of therapy. Fifteen of 19 episodes of serious methicillin-resistant S. aureus infection responded to vancomycin. Severe toxic effects included tinnitus, neutropenia, rash, and possible nephrotoxicity. Tolerance (a minimal bactericidal concentration to minimal inhibitory concentration ratio of at least 32), but not a minimal bactericidal concentration of at least 32 mg/L, correlated with therapeutic failure (respectively, p = 0.04 and p = 0.11, Fisher's exact test). Bacteremic infections due to methicillin-resistant and methicillin-sensitive S. aureus cause similar morbidity and mortality. Vancomycin is effective but potentially toxic therapy for most serious infections due to methicillin-resistant S. aureus. In-vitro tests may not predict therapeutic efficacy.

Vancomycin Therapy for Methicillin-Resistant Staphylococcus aureus

Semiquantitative culturing of catheter tips has been used as an index of catheter-related bacteremia. As the sensitivity and predictive values of this test have not been determined, we studied 780 tips from central vein catheters inserted into 440 critically ill patients in an intensive care unit. The results were correlated with clinical data for 30 bacteremic episodes which occurred in these patients, 14 of which were catheter related. When five or more colonies per plate were taken as a positive result, the sensitivity of the method was 92%, and the specificity was 83%. Although the predictive value of a negative result was excellent (99.8%), the predictive value of a positive result was low (8.8%) in our patient population, which had a relatively low incidence of catheter-related bacteremia (2%). We conclude that a semiquantitative culture technique is useful in the diagnosis of bacteremia associated with central vein catheters.

Is semiquantitative culture of central vein catheter tips useful in the diagnosis of catheter-associated bacteremia?

An extensive survey of the in-vitro susceptibility of clinical isolates of Staphylococcus aureus to 18 antimicrobial agents was conducted over three separate periods during 1986-1987 in 14 teaching hospitals in major Australian cities. The survey aimed to document the prevalence of resistance to a wide variety of drugs that are important as antistaphylococcal agents or as epidemiological markers. More than 7500 isolates were examined. Nationally, the prevalence of resistance was 85.3% to penicillin G, 14.4% to methicillin, 14.0% to amoxycillin/clavulanate, 9% to cephalothin, 5.4% to cephamandole, 9.9% to cefotaxime, 25.0% to erythromycin, 11.2% to clindamycin, 21.7% to tetracycline, 13.0% to gentamicin, 1.9% to amikacin, 5.8% to chloramphenicol, 18.3% to trimethoprim, 0.6% to rifampicin, 3.0% to fusidic acid and 1.2% to novobiocin. For none of the strains was resistance to vancomycin confirmed by minimal-inhibitory-concentration determination. A high proportion of the resistances was harboured in methicillin-resistant Staph. aureus, except for resistance to penicillin G, erythromycin and tetracycline. The prevalence of methicillin resistance varied widely among the states: 25.2% in Queensland, 23.5% in Victoria, 12.6% in New South Wales/the Australian Capital Territory, 11.3% in South Australia and 0.4% in Western Australia. Isolates from blood cultures were slightly-more susceptible to antimicrobial agents than were isolates from other body sites. Six common profiles of resistance to penicillin G, methicillin, erythromycin, clindamycin and tetracycline accounted for more than 95% of the isolates that were tested against all five agents. Vancomycin remains the most important antistaphylococcal drug in areas where resistance to methicillin is common.

A national survey of antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals.

Aeromonas septicemia: relationship of species and clinical features.

Seventy-five episodes of bacteraemia or fungaemia related to indwelling temporary intravenous devices were assessed by the Infectious Diseases Unit of The Westmead Centre, to determine the quality of care of these devices. The estimated incidence of systemic sepsis was 1% for all central venous catheters inserted and 0.1% for all peripheral venous catheters inserted. Sepsis was a major cause of death in 14 of 17 patients who died. Despite the existence of protocols for the insertion, management and early removal of intravenous devices, factors increasing the risk of sepsis included delay in the removal of the intravenous device and the presence of thrombophlebitis. Staphylococcus aureus was the most common isolate (41%); antibiotic resistant Gram-negative rods were also common (38%). It is concluded that continued education of resident and nursing staff is essential to minimize the risk of intravenous catheter-related sepsis.

Rosemary Munro

Papers

Vancomycin Therapy for Methicillin-Resistant Staphylococcus aureus

Is semiquantitative culture of central vein catheter tips useful in the diagnosis of catheter-associated bacteremia?

A national survey of antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals.

Aeromonas septicemia: relationship of species and clinical features.

Systemic sepsis and intravenous devices. A prospective survey.