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Query: UMLS:C0035078 (renal failure)
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Laboratory tests that can be helpful in guiding antimicrobial therapy include antimicrobial susceptibility testing, determination of bacterial beta-lactamase production, assay of serum inhibitory and bactericidal activity, and assay of specific antibiotic levels in serum. Susceptibility studies should be performed on any microorganism that is isolated from normally sterile body fluid (blood, cerebrospinal fluid, pleural fluid, synovial fluid) in the presence of clinical evidence of infection. The standardized disk test provides results that should be comparable from laboratory to laboratory. Dilution methods, however, allow determination of the minimum concentration of an agent which inhibits growth (MIC), and this value can be correlated with blood, urine, and other body fluid levels of the antimicrobial agent. Determination of serum bactericidal activity is, in effect, an assay of the activity of antimicrobial-containing serum; it indirectly measures the combined effects of susceptibility of the test organism and serum concentration of the antimicrobial agent. Accurate measurement of serum concentrations of antimicrobials may be important when treatment includes agents that have a narrow margin between their therapeutic and their toxic levels such as the aminoglycosides (especially gentamicin) or in patients with renal failure, who may accumulate unusually high levels of antimicrobials normally excreted by the kidneys.
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PMID:Laboratory tests used to guide antimicrobial therapy. 33 94

Pharmacokinetics of the novel combination of ticarcillin with the beta-lactamase inhibitor clavulanic acid (BRL 28500, Timentin, Betabactyl) was investigated in order to calculate the dose reduction factor (DRF) and elaborate dosage recommendations for patients with varying degrees of renal impairment. Serum and urine levels of ticarcillin and clavulanic acid have been determined following the i.v. application of 3.2 g and 5.2 g BRL 28500 consisting of 3.0 g and 5.0 g ticarcillin, respectively, and 0.2 g of clavulanic acid each. 10 healthy volunteers and 9 patients received the 5.2 g formulation, and 6 normal subjects and 9 patients the 3.2 g formulation. The pharmacokinetics of both components of BRL 28500 behave fairly similarly and provides the combination with a logic basis. The dose reduction factor, being 1 by definition in normal renal function, rises in final renal failure to 2-3 for clavulanic acid and to 4-5 for ticarcillin. A dosis reduction to 1/2-1/4 will roughly produce the same AUC in a patient with terminal renal insufficiency as the normal dosage in a healthy subject. The distribution volume of ticarcillin and clavulanic acid was found to be enlarged probably due to overhydration in this group of patients. The recovery of both BRL 28500 components decreased with impaired renal function. The recovery 6 h after administration of 0.2 g clavulanic acid in the 5.2 g (3.2 g) BRL 28500 formulation fell from 58 +/- 12% (52 +/- 6) in healthy subjects to 25 +/- 14% (25 +/- 13) in patients with renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetic studies on clavulanate potentiated ticarcillin in normal subjects and patients with renal insufficiency. 358 24

Laboratory tests that can be helpful in guiding antimicrobial therapy include antimicrobial susceptibility testing, determination of bacterial beta-lactamase activity, assay of serum inhibitory and bactericidal activity, and assay of specific antibiotic levels in serum. When any microorganism is isolated from a normally sterile body fluid in a patient with clinical evidence of infection, susceptibility studies should be performed. The standardized disk test provides results that should be comparable from laboratory to laboratory but has the disadvantage of yielding results expressed only as susceptible, intermediate, or resistant. In contrast, dilution methods allow determination of the minimal inhibitory concentration of an agent, which can be correlated with blood, urine, and other body fluid levels of the antimicrobial agent. Accurate measurement of serum concentrations of antimicrobial agents is important when the margin between therapeutic and toxic levels is narrow, such as for aminoglycosides or vancomycin, and when a patient has renal failure and may have accumulation of high levels of antimicrobial agents that would normally be excreted by the kidneys.
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PMID:Laboratory tests used to guide antimicrobial therapy. 362 29

Ceftazidime is an aminothiazolyl cephalosporin with potent activity against gram-negative bacteria including multiresistant strains of Pseudomonas aeruginosa. It has limited activity against gram-negative anaerobes, is less active against some gram-positive cocci than other newer beta-lactam compounds and is inactive against Streptococcus faecalis and methicillin-resistant Staphylococcus aureus. Ceftazidime is stable against common plasmid and chromosomally mediated beta-lactamase produced by Enterobacteriaceae and Pseudomonas sp. Its pharmacokinetic properties are similar to those of moxalactam and ceftizoxime, and it has a half-life of 1.9 hours. Excretion is by glomerular filtration. It is not metabolized. Ceftazidime penetrates into most body tissue and fluids, including cerebrospinal fluid, and produces therapeutic levels against most of the pathogenic gram-negative bacteria, including P. aeruginosa. Ceftazidime accumulates during renal failure, but is removed by hemodialysis and peritoneal dialysis. As a single agent it has been shown effectively to treat meningitis; urinary tract infections; gram-negative pneumonia; bone, joint and skin infections; and obstetric and gynecologic infections due to susceptible organisms. When combined with an agent that is effective against gram-positive organisms, it is also beneficial in the treatment of infections in seriously ill neonates. Different investigators have used ceftazidime alone or in combination with other agents in the successful treatment of infections in immunosuppressed patients. Adverse reactions have been few and are mostly reversible laboratory findings. The effects of ceftazidime on prothrombin synthesis and platelet function have been minimal, and no drug-induced clinical bleeding has been reported.
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PMID:Antimicrobial activity, pharmacokinetics, therapeutic indications and adverse reactions of ceftazidime. 390 85

Sulbactam, a beta-lactamase inhibitor, was given as a single agent to 12 subjects with varying degrees of renal dysfunction. The half-life in normal subjects was 1.1 h and increased to 21.3 h in those with terminal renal failure. Sulbactam together with ampicillin was given to a further five subjects. It was concluded that if the two agents are given together, the plasma ratio of one to the other will remain constant whatever the renal function.
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PMID:The elimination of sulbactam alone and combined with ampicillin in patients with renal dysfunction. 630 31

Ceftizoxime is an iminomethoxy aminothiazolyl cephalosporin that inhibits a wide variety of aerobic, anaerobic gram-positive and gram-negative bacteria. The majority of Enterobacteriaceae are inhibited by less than or equal to 1 microgram/ml as are streptococcal species with the exception of Streptococcus faecalis. Staphylococcus aureus are inhibited by 3-8 micrograms/ml, while methicillin-resistant. aureus are resistant. Bacteroides fragilis are inhibited by 16-64 micrograms/ml. It inhibits Pseudomonas aeruginosa at usually achievable concentrations. Ceftizoxime is overall similar in antibacterial activity to cefotaxime and moxalactam. Ceftizoxime is not hydrolyzed by common plasmid and chromosomal beta-lactamases. Serum levels of ceftizoxime after intramuscular and intravenous injection are similar to those of cefotaxime and moxalactam. The half-life is 1.6 to 1.9 hours in normal individuals. The compound is not metabolized and is cleared from the body by glomerular filtration. Ceftizoxime enters most body fluids, including the cerebrospinal fluid, to produce therapeutic concentrations against clinically important bacteria. Ceftizoxime accumulates in the presence of renal failure, but it is removed from the body by hemodialysis and peritoneal dialysis. Ceftizoxime has proved to be an effective chemotherapeutic agent when used as treatment for pneumonia, urinary tract infections, osteomyelitis, septic arthritis, meningitis, peritonitis, gonorrhea, including penicillinase-producing isolates, and gynecological infections. No major adverse reactions have been associated with the use of ceftizoxime and it has produced neither disulfram -like reactions nor bleeding.
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PMID:Ceftizoxime: a beta-lactamase-stable, broad-spectrum cephalosporin. Pharmacokinetics, adverse effects and clinical use. 632 62

Laboratory tests that can be helpful in guiding antimicrobial therapy include antimicrobial susceptibility testing, determination of bacterial beta-lactamase production, assay of serum inhibitory and bactericidal activity, and assay of specific antibiotic levels in serum. Susceptibility studies should be performed on any microorganism that is isolated from normally sterile body fluid in the presence of clinical evidence of infection. The standardized disk test provides results that should be comparable from laboratory to laboratory. Dilution methods, however, allow determination of the minimal concentration of an agent which inhibits growth, and this value can be correlated with blood, urine, and other body fluid levels of the antimicrobial agent. Determination of serum bactericidal activity is, in effect, an assay of the activity of antimicrobial-containing serum; it indirectly measures the combined effects of susceptibility of the test organism and serum concentration of the antimicrobial agent. Accurate measurement of serum concentrations of antimicrobial agents may be important when treatment includes agents that have a narrow margin between therapeutic and toxic levels such as the aminoglycosides (especially gentamicin) or in patients with renal failure, who may accumulate unusually high levels of antimicrobial agents normally excreted by the kidneys.
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PMID:Laboratory tests used to guide antimicrobial therapy. 633 7

Temocillin is a new penicillin combining activity against Gram-positive organisms, beta-lactamase stability and an exceptionally long half-life. In patients with normal renal function the half-life was approximately 4-6 h and this increased to 30 h in patients with severe renal failure. It is suggested that unlike other penicillins this compound may give adequate antibacterial concentration with once daily dosing in subjects with normal renal function; this will certainly require reduction in subjects with severely impaired renal function.
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PMID:Temocillin elimination in patients with varying degrees of renal failure. 687 33

Antipseudomonal penicillins retain most of the antibacterial activity of penicillin and aminopenicillins. This group of penicillins has added activities against many gram-negative rods, including P. aeruginosa. Similar to the earlier penicillins, this group continues to be susceptible to hydrolysis by many beta-lactamases and are, therefore, not consistently active against Staphylococcus, some gram-negative rods, and certain beta-lactamase-producing gram-negative anaerobes. The ureidopenicillins, especially piperacillin, appear to have better activity against Enterococcus, Klebsiella, and P. aeruginosa than ticarcillin. The advantages over the newer cephalosporins are (1) better activity against Enterococcus, (2) more consistent activity against Clostridium, and (3) more consistent synergy with aminoglycosides. The ureidopenicillins have certain advantages over carboxypenicillins, including lower sodium load, less frequent hypokalemia, reduced platelet dysfunction, minimal dosage adjustment in patients with renal failure, and a wider spectrum of antibacterial activity, especially against Enterococcus, Pseudomonas, and Klebsiella. The utility of the antipseudomonal penicillins by themselves is limited as agents for monotherapy when the infecting organism is not known. In addition, monotherapy is not recommended in certain infections to avoid the development of resistance. When combined with a beta-lactamase inhibitor or with an aminoglycoside, however, some of the weaknesses can be overcome.
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PMID:Antipseudomonal penicillins. 779 16

An aminoglycoside- and ceftazidime-resistant strain of Klebsiella pneumoniae K2 producing the extended-spectrum beta-lactamase SHV-5 infected or colonized 14 pediatric patients at Guy's Hospital. The patients were mostly neonates recovering from cardiac surgery for congenital defects. The organism was also isolated from a nurse and from the father of one of the children. Four patients had septicemia, and two septicemic neonates with postoperative renal failure died. Aminoglycoside and cephalosporin resistance transferred to Escherichia coli in vitro on a 160-kb plasmid, and a similar resistant E. coli strain was isolated from the stools of one of the affected children. The epidemic organism colonized the bowel and skin and was probably transmitted via staff hands. Five wards were involved because of extensive patient movements. The outbreak was controlled by patient isolation and attention to handwashing. All of the isolates of the outbreak strain were identical by phage typing, ribotyping, plasmid profiling, and biochemical and serological testing, but they varied in their production of SHV-5. Some isolates produced normal amounts of SHV-5 and were susceptible to beta-lactam-beta-lactamase inhibitor combinations. Others, including the single isolate of multiresistant E. coli, produced up to five times as much enzyme as "normal" isolates. This hyperproduction resulted in increased resistance to several penicillins and cephalosporins and to the beta-lactam-beta-lactamase inhibitor combinations amoxicillin-clavulanic acid, ampicillin-sulbactam, piperacillin-tazobactam, and ceftazidime-clavulanic acid. The hyperproduction of SHV-5 by K. pneumoniae and E. coli seen in this outbreak suggests that beta-lactam-beta-lactamase inhibitor combinations may be unreliable for the treatment of organisms producing extended-spectrum beta-lactamases.
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PMID:Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV-5 beta-lactamase. 878 16


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