Emergence of Antibiotic Resistance during Therapy for Infections Caused by Enterobacteriaceae Producing AmpC β-Lactamase: Implications for Antibiotic Use
Antibiotic therapy for inducible AmpC β-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglyc... - PubMed - NCBI
●Gram-negative bacilli are the cause of approximately a quarter to a half of all bloodstream infections, depending on geographic region, hospital- or community-onset, and other patient risk factors. Most hospitalized patients with gram-negative bacteremia have at least one comorbid condition, such as diabetes, liver or kidney failure, and immunosuppression.
●The frequency of specific gram-negative bacilli responsible for bacteremia differs by whether the onset of the infection is in the hospital or community and by the likely primary source of infection. As an example, Pseudomonas aeruginosa is a frequent pathogen in hospital-onset infections, particularly those that occur in intensive care unit patients. In contrast, community-acquired infections are most often secondary to urinary tract infections, among which Escherichia coli predominate.
Clinical manifestations and diagnosis
●Patients with gram-negative bacillary bacteremia typically present with fever. Disorientation, hypotension, and respiratory failure may complicate bacteremia and are usually signs that the patient may be developing septic shock, which is seen in about 25 percent of patients on presentation with gram-negative rod bacteremia.
●Gram-negative bacillary bacteremia rarely occurs spontaneously without infection at another site, and thus additional clinical manifestations will vary by the site of the primary infection. Exceptions include neutropenic patients, among whom cytotoxic chemotherapy can cause mucosal injury that allows bacteria to cross mucosal membranes and enter the bloodstream, and central venous catheter-related infections that can present without an obvious exit site infection.
●Gram-negative bacillary bacteremia is diagnosed when there is growth of a gram-negative bacillus on blood culture. Obtaining and interpreting blood cultures when bacteremia is suspected is discussed in detail elsewhere.
●The treatment of gram-negative bacteremia is increasingly complicated by the occurrence of multidrug resistant gram-negative bacilli strains, which is substantial and increasing. Additionally, multidrug-resistant pathogens are no longer limited to acute care hospitals and frequently infect or colonize patients in the community who have significant healthcare exposures and those in long-term care facilities．
●Treatment of gram-negative bacillary bacteremia includes urgent empiric antibiotics, supportive care, careful monitoring of patients, and control of the source of infection, which may require surgical drainage or removal of an intravascular catheter.
●The choice of empiric antibiotics should consider the patient's history, including recent antimicrobial exposure, comorbidities, clinical syndrome, prior healthcare exposures, Gram stain data, and previous culture results. Other important management decisions include whether to empirically cover P. aeruginosa or other multidrug-resistant organisms and when to employ combination antimicrobial therapy．
●For patients with gram-negative bacillary bacteremia who do not have signs of severe sepsis or septic shock, recommended regimens depend on the presence of immune suppression or healthcare exposures. Example regimens are listed above.
•For empiric therapy of immunocompetent patients without healthcare exposures, we recommend a single broad-spectrum antibiotic (Grade 1B). Antipseudomonal activity is generally not necessary.
•For empiric therapy of patients with immunosuppression or healthcare exposures, we recommend a single broad-spectrum antibiotic with antipseudomonal activity (Grade 1B).
・Although there are no direct data demonstrating benefit of combination therapy, use of two agents increases the likelihood that empiric therapy will be effective against the infecting organism. Thus, we favor combination antimicrobial therapy in a select subset of patients who are most likely to have an infection with a drug-resistant organism and for whom inappropriate antibiotic therapy would presumably be associated with an especially high mortality:
•Therefore, for patients with severe sepsis or septic shock in the setting of gram-negative bacteremia who also have immunosuppression, have other risk factors for P. aeruginosa, or are at hospitals where the level of resistance to the chosen empiric gram-negative agent among the most common gram-negative pathogens exceeds 20 to 25 percent, we suggest empiric therapy with a combination of two antipseudomonal agents (Grade 2C).
•For patients with severe sepsis or septic shock in the setting of gram-negative bacteremia who do not have any of these additional risk factors for resistant organisms, we recommend treatment with a single antipseudomonal agent (Grade 1B).
Example regimens are listed above.
●Once culture results and antimicrobial susceptibility data are available, we typically narrow coverage so that therapy is pathogen-directed based upon the susceptibility results. The duration of therapy should be determined by the clinical response of the patient and the source and extent of infection.
●The reported mortality rate of patients with gram-negative bacteremia ranges from 12 to 38 percent. This is even higher among those who also have severe sepsis. Although difficult to assess, infection with drug-resistant organisms is associated with greater mortality, as well.
Duration of therapy —
No randomized controlled studies have evaluated the optimal duration of antibiotic therapy for gram-negative bacteremia; the duration of therapy should be determined by the clinical response of the patient in addition to the primary source and extent of infection.
In most cases, the duration of antibiotic therapy is 7 to 14 days. Initially antibiotics should be given parenterally, but once the patient has defervesced and has remained afebrile for 48 hours, the antibiotics may be switched to an oral agent with in vitro activity and excellent bioavailability.
Catheter removal —
Catheter-related gram-negative bacteremia often requires removal of the catheter to prevent relapse of infection. Long-term catheters should be removed in the setting of severe sepsis, suppurative thrombophlebitis, endocarditis, bacteremia that continues despite >72 hours of appropriate antimicrobial therapy, or infection due to P. aeruginosa． Otherwise, line salvage can be attempted in the setting of uncomplicated catheter-related bacteremia due to gram-negative pathogens (other than P. aeruginosa) with 10 to 14 days of systemic therapy coupled with antibiotic lock therapy.
Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Soc... - PubMed - NCBI