Antimicrobial agent therapy for Pseudomonas aeruginosa

Korvick, Joyce A.; Yu, Victor L.

doi:10.1128/aac.35.11.2167

Cited by 60 publications

(34 citation statements)

References 78 publications

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“…They failed to demonstrate a direct correlation between quantitative in vitro susceptibility test results and therapeutic outcome. A current review by Korvick and Yu highlights the problem of interpreting in vitro susceptibility test results for this pathogen (60). Similar results were reported by Van der Auwera et al for immunocompromised patients infected with gram-positive bacteria and treated with vancomycin or teicoplanin (113).…”

Section: Introduction Introductionsupporting

confidence: 73%

“…The microbiology laboratory's approach to susceptibility testing, as it relates to the management of infectious diseases, is the topic of many reports (17, 24, 37, 38, 47, 49, 51, 55,60,73,74,94,111). The questions facing clinical microbiologists are how to best perform such in vitro tests and which ones are most useful for guiding therapy for the infected patient (12,98).…”

Section: Introduction Introductionmentioning

confidence: 99%

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Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

1992

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Bactericidal testing has been used for several decades as a guide for antimicrobial therapy of serious infections. Such testing is most frequently performed when bactericidal antimicrobial agent therapy is considered necessary (such as when treating infectious endocarditis or infection in an immunocompromised host). It has also been used to ensure that the infecting organism is killed by (not tolerant to) usually bactericidal compounds. However, few data are available to support the role of such tests in direct patient care. Several important variables affect the reproducibility of the test results; however, proposed reference methods are now available for performing the MBC test. With minor modifications, these can provide a standardized approach for laboratories that need to perform them. Currently, little evidence is available to support the routine use of such testing for the care of individual patients. However, testing of new (investigational) antimicrobial agents can be beneficial in determining their potential to provide bactericidal antimicrobial activity during clinical use. New methods to assess bactericidal activity are being developed, but as yet none have been rigorously tested in patient care settings; further, for most of these methods, little information is available as to which technical parameters affect their results. In clinical laboratories, all bactericidal tests must be performed with rigorously standardized techniques and adequate controls, bearing in mind the limitations of the currently available test procedures.

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Section: Introduction Introductionsupporting

confidence: 73%

Section: Introduction Introductionmentioning

confidence: 99%

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

1992

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“…Receipt of nebulized medications, invasive procedures, and exposure to contaminated hospital water supplies and medications are additional risk factors (2,9,18,21). All the ICU patients infected by the clonal strain of P. aeruginosa were treated with the combination of cefepime plus amikacin, rather than with the classic ceftazidime-amikacin combination (22) because, by MIC determination, cefepime appeared to be more active than ceftazidime. Moreover, the imipenem resistance complicated the choice of an antipseudomonal treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, acquired resistance are particularly frequent in P. aeruginosa, and the difficulty of finding an effective treatment increases the mortality and the morbidity of P. aeruginosa-induced infections in hospitalized patients. The combination of ceftazidime plus amikacin is considered the first-choice antipseudomonal chemotherapy (22). Even the "fourth-generation" cephalosporins, cefpirome and cefepime, which have a higher degree of activity against gram-negative organisms, are less efficient in vitro than ceftazidime on P. aeruginosa (40).…”

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Nosocomial Outbreak Due to a Multiresistant Strain of Pseudomonas aeruginosa P12: Efficacy of Cefepime-Amikacin Therapy and Analysis of β-Lactam Resistance

et al. 2001

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Over a 3-year period, 67 patients of the Hospital of Pau (Pau, France), including 64 patients hospitalized in the adult intensive care unit (ICU), were colonized and/or infected by strains of Pseudomonas aeruginosa P12, resistant to all potentially active antibiotics except colistin. Most patients were mechanically ventilated and presented respiratory tract infections. Since cefepime and amikacin were the least inactive antibiotics by MIC determination, all ICU patients were treated with this combination, and most of them benefited. Cefepimeamikacin was found highly synergistic in vitro. Ribotyping and arbitrary primer-PCR analysis confirmed the presence of a single clonal isolate. Isoelectrofocusing revealed that the epidemic strain produced large amounts of the chromosomal cephalosporinase and an additional enzyme with a pI of 5.7, corresponding to PSE-1, as demonstrated by PCR and sequencing. Outer membrane protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the absence of a ca. 46-kDa protein, likely to be OprD, and increased production of two ca. 49-and 50-kDa proteins, consistent with the outer membrane components of the efflux systems, MexAB-OprM and MexEF-OprN. Thus, we report here a nosocomial outbreak due to multiresistant P. aeruginosa P12 exhibiting at least four mechanisms of ␤-lactam resistance, i.e., production of the penicillinase PSE-1, overproduction of the chromosomal cephalosporinase, loss of OprD, and overexpression of efflux systems, associated with a better activity of cefepime than ceftazidime.Pseudomonas aeruginosa, like many other nonfermenting gram-negative rods, is a saprophytic organism widespread in nature, particularly in moist environments (water, soil, plants, and sewage), and endowed with only weak pathogenic potential. However, because of its ability to survive on inert materials and its resistance to most antiseptics and antibiotics, P. aeruginosa has become an important and frequent nosocomial pathogen. Indeed, in hospitals, sinks, respiratory therapy equipment, and antiseptic or detergent solutions can act as reservoirs of P. aeruginosa. This organism is responsible for a wide range of hospital-acquired infections such as pneumonia, urinary tract infections, or bacteremia. Patients with impaired specific or nonspecific defense systems particularly tend to suffer from severe and even fatal infections caused by P. aeruginosa (9,11,23,24). Cross-transmission from patient to patient may occur via the hands of the health care staff or through contaminated materials or reagents (2, 18, 21, 24). Thus, a number of outbreaks of nosocomial infections due to P. aeruginosa have been reported, especially in intensive care units (ICUs) (2, 11, 18, 24), burn wound units (21), and cancer centers (23).One feature of P. aeruginosa is its high level of intrinsic resistance to a number of structurally unrelated antimicrobial agents. Indeed, the broad-spectrum resistance of this organism is largely due to a low outer-membrane permeability (32,33) and to multidrug...

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“…Infections caused by P. aeruginosa are difficult to treat because of the organism's intrinsic resistance to many antibiotics and its propensity to develop resistance during therapy (10,(13)(14)(15)(16)(17). These properties have so limited the effectiveness of antibiotic monotherapy that combination antibiotic therapy has been advocated for serious P. aeruginosa infection (1,11,13,19).…”

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confidence: 99%

Addition of rifampin to combination antibiotic therapy for Pseudomonas aeruginosa bacteremia: prospective trial using the Zelen protocol

Korvick

Peacock

Muder

et al. 1992

Antimicrob Agents Chemother

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A multicenter, prospective randomized trial was conducted to determine if the addition of rifampin to a combination therapy of an antipseudomonal beta-lactam agent and aminoglycoside improves the outcome of patients with Pseudomonas aeruginosa bacteremia. The Zelen protocol for randomized-consent design was used. Consent was sought only from patients randomized to the experimental therapy (rifampin+). If the experimental therapy was refused, the patient would then receive the standard combination therapy (control); however, when outcome was evaluated, all patients randomized to the rifampin+ group, including those that declined rifampin, were compared with the control group. One hundred twenty-one consecutive hospitalized patients with positive blood cultures for P. aeruginosa were enrolled. Entry was stratified for prior use of empiric antipseudomonal antibiotics, neutropenia, severity of illness, and presence of pneumonia. Fifty-eight patients were randomized to receive rifampin (600 mg orally every 8 h for the first 72 h and then every 12 h for a total of 10 days) plus a beta-lactam agent plus an aminoglycoside. Sixty-three received the standard therapy of a beta-lactam plus an aminoglycoside agent (control). Bacteriologic cure occurred significantly more frequently in patients randomized to the rifampin+ regimen. Breakthrough or relapsing bacteremias occurred in 2% of the three-drug (rifampin+) group, compared with 14% for the two-drug (standard therapy) group. Despite this favorable trend in bacteriological response, no significant differences in survival were seen for the two treatment groups. Rifamycin derivatives warrant further clinical study as antipseudomonal agents. The Zelen protocol appears well suited for comparative trials of antimicrobial agents.Pseudomonas aernginosa continues to be an important pathogen, especially among debilitated and immunocompromised individuals. Infections caused by P. aeruginosa are difficult to treat because of the organism's intrinsic resistance to many antibiotics and its propensity to develop resistance during therapy (10,(13)(14)(15)(16)(17). These properties have so limited the effectiveness of antibiotic monotherapy that combination antibiotic therapy has been advocated for serious P. aeruginosa infection (1,11,13,19). Nevertheless, the mortality rates for bacteremia due to P. aeruginosa continue to be consistently higher than for other bacterial pathogens (1,3,5,8).In an exploration for more potent antipseudomonal combinations of antibiotics, rifampin was found to be synergistic in vitro with antipseudomonal penicillin and an aminoglycoside against P. aeruginosa (20,22,26). Compared with the double combination of an antipseudomonal beta-lactam agent and an aminoglycoside, a triple combination of rifampin, an antipseudomonal beta-lactam agent, and an aminoglycoside significantly improved survival in neutropenic mice infected with P. aeruginosa (9,21,25). Moreover, selected patients with P. aeruginosa sepsis who failed standard antipseudomonal combination therapy w...

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Antimicrobial agent therapy for Pseudomonas aeruginosa

Cited by 60 publications

References 78 publications

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

Nosocomial Outbreak Due to a Multiresistant Strain of Pseudomonas aeruginosa P12: Efficacy of Cefepime-Amikacin Therapy and Analysis of β-Lactam Resistance

Addition of rifampin to combination antibiotic therapy for Pseudomonas aeruginosa bacteremia: prospective trial using the Zelen protocol

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