The Intensive Care Manual - part 5 pps

Organ Transplantation Organ transplant recipients are immunosuppressed for a variety of reasons. 58 These include use of immunosuppressive drugs to minimize rejection of the transplant, broken mucocutaneous barriers (e.g., from catheters), infection with immunomodulating viruses (i.e., CMV, Epstein-Barré virus, hepatitis B and C viruses, HIV), and metabolic derangements. In general, the approach to infection in the organ transplant recipient is similar to that already outlined for immuno- competent patients. Pulmonary infection is known to be the most common infection encountered in this group. The risk should be stratified by time from transplantation. In the first month after transplant, the vast majority of infections are nosocomial bacterial infections of the lungs or candidal and bacterial wound, urinary tract, or vascular catheter infections. The approach to each has already been outlined. In the period from 1 to 6 months after transplant, the doses of immunosuppressive drugs are higher than in ensuing months and many of the im- munomodulatory viruses reactivate endogenously or from the transplanted organ. When CMV is transplanted with the solid organ into the previously non- immune host, it reactivates in that organ and causes clinical disease in the recipient. In concert with this reactivation, opportunistic pathogens emerge including Listeria monocytogenes, Nocardia asteroides, Mycobacterium tuberculosis, Pneumo- cystis carinii, Asperillus fumigatus, Cryptococcus neoformans, and far less commonly than in AIDS, Toxoplasma gondii. In the recipient of a bone marrow allograft, CMV reactivates and replicates in pulmonary macrophages. The engrafted marrow recognizes pulmonary macrophages, which are supporting replication of CMV, as being more foreign and hence CMV pneumonitis parallels graft versus host disease. Once the recipient has survived 6 months past the transplant date, the risk of infection is similar to the general population with the exception of those under- going recurrent or chronic rejection. This puts them back into the 1- to 6-month risk group. ANTIMICROBIAL RESISTANCE Drug-resistant organisms are isolated more commonly from patients in the ICU than from general hospital or community patients. 59 Bacteria with resistance to antibiotics are prevalent in the ICU because of the use of broad-spectrum antibiotics. When a patient is treated with an antibiotic, their normal flora is sup- pressed, allowing the nosocomial organisms, which are transferred between patients on the hands of personnel or on devices, to take over the mucosal sur- faces. These nosocomial organisms survive in the ICU because of their antibiotic resistance. In addition, via genetic transfer, they can donate resistance genes to organisms from another strain. Furthermore, these nosocomial organisms ad- here, via a biofilm, to the tubes and catheters that are inserted into the patients. If 6 / Infectious Disease 153 ch06.qxd 11/7/01 4:13 PM Page 153 a specific patient has not received antibiotics, he or she is less likely to be colo- nized by resistant organisms because the presence of normal flora excludes the nosocomial organisms. Physicians caring for patients in the ICU should be familiar with risks of infection with resistant organisms and preventative measures. The best ways to curb the spread of resistance are observing good infection control practices (chiefly wearing gloves and washing hands between patient en- counters) and limiting the use of and appropriate selection of antibiotic agents. The Society for Healthcare Epidemiology of America and Infectious Diseases So- ciety of America have published guidelines for the prevention of antimicrobial resistance. 60 To treat infections caused by resistant organisms, it is first essential that a physician be familiar with local rates of resistance. If MRSA has not yet become a significant problem in a given hospital, vancomycin should not be a part of the empiric therapy for nosocomial infections in the ICU. The following national rates may be useful, but do not substitute for local data. Methicillin-Resistant Staphylococcus aureus S. aureus is a major cause of nosocomial infections in the ICU, especially VAP and catheter-related bloodstream infection. S. aureus resistance to methicillin is mediated through an altered penicillin-binding protein (mec A). Among the resistant bacterial species, it is the most virulent pathogen. In a 1997 surveillance study of more than 5,000 isolates causing bloodstream infection from multiple centers in the United States and Canada, methicillin resistance was found in 26.2% of U.S. isolates. 61 It was present in 46.7% of isolates from the ICU col- lected by the NNIS in 1998. 62 The characteristics of patients at highest risk for infection with MRSA are that they are older people, have recently been hos- pitalized, have severe underlying disease, have recently used antibiotic agents, and are on mechanical ventilation for pneumonia. 63 Vancomycin is the treatment of choice in MRSA infection. Newer agents such as quinupristin-dalfopristin (Synercid) or linezolid are likely to prove clinically useful in the future. Vancomycin should be used as part of empiric therapy in patients at high risk for MRSA infection in hospitals where the prevalence is high. Vancomycin-Resistant Enterococci Vancomycin-resistant enterococcus (VRE) was first reported in the mid-1980s. Since then, the prevalence of VRE has steadily increased. The NNIS Antimicro- bial Resistance Surveillance Report found that in the first 11 months of 1998, 23.9% of enterococcal isolates from the ICU were vancomycin-resistant. 62 In- creasing vancomycin use has led to increasing resistance. Risk factors for infection with VRE include proximity to patients infected with VRE, hospitalization in an ICU, immunocompromised status, and exposure to antibiotics, including vancomycin, cephalosporins, metronidazole, and clindamycin. 64 Barrier isolation 154 The Intensive Care Manual ch06.qxd 11/7/01 4:13 PM Page 154 and the use of devoted medical instruments, such as individual glass thermome- ters and stethoscopes, is indicated. Most importantly, extremely careful hand- washing after patient contact is required. Resistance is conferred through an alternate set of genes that encode for en- zymes that synthesize new cell-wall precursors. These cell-wall precursors end in D -alanine-lactate, instead of the usual D-alanine-alanine, which is the binding site of vancomycin. The importance of VRE infection is debated. In general, enterococci are not virulent organisms. They chiefly cause UTI and abdominal wound-related bacteremia. Some strains are susceptible to tetracyclines, chloramphenicol, rifampin, or ciprofloxacin, and several of these used in combination are sometimes effective. There are several drugs that show promise for activity against VRE. These include quinupristin/dalfopristin (Synercid), oxazolidinones, and evernino- mycin. The greatest risk with VRE is that it will confer its resistance, which can be found in genes on a transposon or on chromosomes, to other species of bacteria. Drug-Resistant Streptococci Drug-resistant S. pneumoniae (DRSP) is a fairly recent entity in the United States. In 1989 the rate of penicillin-resistance overall was 3.8%. 65 Virtually all of this was intermediate resistance; minimum inhibitory concentration (MIC) is 0.12 to 1 µg/mL. By 1992 the combined intermediate-level and high-level resistance (MIC, > 1 µg/mL) rose to 17.8%. A 30-center surveillance study found 24.6% resistance, with a full one-third being high-level in 1994. 66 The most recent prevalence study, conducted with more than 1600 isolates from the U.S. and Canada in 1997, revealed an overall penicillin-resistance rate of 43.8%, with 27.8% intermediate and 16.0% high-level. 67 In this study, 18.1% of the organisms were resistant to amoxicillin; 4%, to cefotaxime; 11.7% to 14.3%, to macrolides; and 19.8% to TMP/SMX. The rate of increase is alarming. Penicillin resistance is mediated by alterations in the penicillin-binding proteins. There is some cross-resistance with all beta-lactam antibiotics. The rise in penicillin resistance has been observed to coincide with a rise in resistance to other classes of antibiotics and multiply resistant strains. This is probably caused by selective pressure of antimicrobial use for a relatively few strains of resistant S. pneumoniae. Risks for DRSP infection have been identified from several population studies. Risk factors include age, recent antimicrobial therapy, coexisting illness or underlying disease, HIV infection, immunodeficient status, recent or current hospitalization, and being institutionalized. Patients in the ICU have some of these factors. The clinical relevance of intermediate and high-level resistance to S. pneumoniae is unclear. When empirically treating infections like community- acquired pneumonia in the ICU, awareness of local rates of drug resistance is imperative. In outcome studies, penicillin is effective in cases in which the pneumococci have intermediate resistance and in cases where the pneumococci 6 / Infectious Disease 155 ch06.qxd 11/7/01 4:13 PM Page 155 are highly sensitive. If high-level penicillin resistance is suspected based on local patterns and individual risk factors, vancomycin may be used empirically until susceptibility test results are obtained. Antibiotic-Resistant Gram-Negative Bacteria Gram-negative organisms, which seldom cause disease in the community, are major colonizers in ICU patients and, given the right set of circumstances, cause disease in this group. Examples of this include Pseudomonas aeruginosa and Acinetobacter baumanii. When these organisms first appear as colonizers in the ICU, they are generally susceptible to the aminoglycoside antibiotics, piperacillin, ceftazidime, and imipenem-cilastatin. However, as these patients are given antibiotics to suppress the colonization, greater resistance ensues. In some in- stances, these organisms become resistant to all available antibiotics. If the clinician uses antibiotics to curb these organisms only when true infection occurs, evolution to complete resistance is slowed. Klebsiella species are one of the better examples of acquisition of genes that allow emergence of resistance. Enterobacter species transfer resistance genes to the members of the Klebsiella tribe, which become resistant to all the beta-lactam antibiotics. Controlling the use of these antibiotics often eliminates the organisms from the ICU. Stenotrophomonas maltophilia is a nonfermenting gram-negative bacterium, which is highly antibiotic-resistant and rarely causes infection in the community or in normal hosts. It has become an important organism in the ICU largely because it is resistant to imipenem-cilastatin and aminoglycosides. It causes ventilator-related pneumonia, bacteremia, and UTI. It is sensitive to high doses of TMP/SMX, ticarcillin-clavulanate, and unpredictably, to certain beta-lactam agents. In vitro susceptibility test results do not predict in vivo success. ANTIBIOTICS Penicillins The penicillin class of antibiotics contains many different drugs that are useful in the treatment of infections in the ICU. 68 They share a mechanism, which is inhibition of synthesis of the bacterial cell wall and activation of the endogenous autolytic system of bacteria. The class shares its adverse effect profile. Most common is allergic or hypersensitivity reaction, occurring in 3% to 10% of the general population. These reactions can range from rash to anaphylaxis and include drug fever and interstitial nephritis. Less commonly psuedomembranous colitis, hepatotoxicity, seizures, and hypokalemia may occur. Most penicillins are not metabolized, are excreted by the kidneys, and require dose adjustment in renal failure (except for oxacillin, nafcillin, and ureidopenicillins). 156 The Intensive Care Manual ch06.qxd 11/7/01 4:13 PM Page 156 AMINOPENICILLINS (AMPICILLIN, AMOXICILLIN, BACAMPICILLIN) The aminopenicillin (ampicillin, amoxicillin, bacampicillin) group is notable for its activity against gram-negative bacteria. There is activity against S. pneumoniae (but with growing resistance), Hemophilus influenzae, enterococci, and gram- negative bacteria, such as E. coli and Proteus and Listeria species. Absent from the spectrum is activity against S. aureus and Klebsiella, Serratia, Enterobacter, and Pseudomonas species. UTI with susceptible organisms may be treated with ampicillin. PENICILLINASE-RESISTANT PENICILLINS (OXACILLIN, NAFCILLIN) The penicillinase-resistant penicillins (oxacillin, nafcillin) have a narrow spectrum of activity for gram-positive organisms. They are the treatment of choice for infections with Staphylococcus species. There is no activity against gram-negative bacteria. There is spreading resistance in S. aureus, a major ICU pathogen. In susceptible strains, this class is an excellent choice for the treatment of bloodstream infection, sinusitis, and pneumonia. UREIDOPENICILLINS (PIPERACILLIN, MEZLOCILLIN, AZLOCILLIN) Urei- dopenicillins (piperacillin, mezlocillin, azlocillin) have activity against most major gram-negative ICU pathogens, including E. coli and Klebsiella, Serratia, Proteus, and Pseudomonas species. They retain activity against streptococci and enterococci, but not beta-lactamase–producing S. aureus or H. influenzae. There is additional coverage against many anaerobic bacteria. Piperacillin is an excellent choice in the empiric treatment of gram-negative pneumonia or sinusitis, in combination with an aminoglycoside. AMPICILLIN-SULBACTAM The spectrum of this drug, while broad, lacks coverage for many E. coli and for Pseudomonas and Serratia species. It should not be used empirically in critically ill patients with suspected bacteremia or pneumonia. PIPERACILLIN-TAZOBACTAM Tazobactam adds to the activity of piperacillin by including methicillin-sensitive S. aureus, E. coli, and most Klebsiella species, which are resistant to piperacillin, and many anaerobic bacteria. This is an excellent drug for empiric coverage of sepsis from an unknown source or as a second- line agent in pneumonia, sepsis, or UTI. Cephalosporins The cephalosporin class of antibiotics is among the most used in the ICU. 69 The mechanism of action is the same as penicillin, i.e., binding to penicillin-binding proteins in the cytoplasmic membrane of bacteria and interfering with cell-wall synthesis. They also activate the autolytic system of bacteria. The drugs are generally well-tolerated, even though the known adverse effects are numerous. One to three percent of patients have a hypersensitivity or allergic reaction to the drug. 6 / Infectious Disease 157 ch06.qxd 11/7/01 4:13 PM Page 157 Anaphylaxis is rare. C. difficile colitis may be seen after cephalosporin use. Un- common effects include eosinophilia, thrombocytopenia, nausea, vomiting, and hypoprothrombinemia and thrombophlebitis with intravenous administration. Cephalosporins are generally excreted in the urine and should be dose-adjusted in renal failure. The spectrum is given here for representative members of each generation that are commonly used in the ICU. No member of the class is a reli- able agent against anaerobic infections. FIRST-GENERATION (CEFAZOLIN) Cefazolin has a very narrow spectrum of antibacterial activity. It is active against MRSA and also E. coli, Klebsiella pneumoniae, and Proteus mirabilis. It may be used for the treatment of bacteremia, pneumonia, or sinusitis with proven-sensitive S. aureus. SECOND-GENERATION (CEFUROXIME) Cefuroxime has better activity than cefazolin against E. coli, Klebsiella species, and P. mirabilis. It has less activity against S. aureus, but adds coverage for S. pneumoniae. Again, many of the common ICU pathogens are not covered. In general, there is little use for this drug in the ICU setting. THIRD-GENERATION (CEFTRIAXONE, CEFTAZIDIME) Ceftriaxone has activity against S. pneumoniae, Klebsiella, E. coli, P. mirabilis, and H. influenzae. It is active against the typical bacteria that cause community-acquired pneumonia in the ICU. Many physicians use a macrolide with ceftriaxone to include the “atypi- cals” in the spectrum. A fluoroquinolone may be substituted for the macrolide. Ceftriaxone’s lack of pseudomonal coverage prevents its empiric use for infections acquired in the ICU. Ceftazidime has activity similar to that of ceftriaxone against Hemophilus or Moraxella species and adds pseudomonal coverage. However, it lacks effective activity against S. pneumoniae or anaerobes, so it should not be used for community-acquired pneumonia. It may be used empirically in combination with another anti-pseudomonal drug for gram-negative sinusitis, gram-negative ventilator-associated pneumonia, sepsis of unknown cause, and neutropenic fever. FOURTH-GENERATION (CEFEPIME) Cefepime is the other cephalosporin with activity against Pseudomonas species. It has enhanced activity against S. pneumoniae. Its uses are similar to ceftazidime. It may be used as monotherapy for neutropenic fevers, if catheter-related bloodstream infection is not suspected. Vancomycin Vancomycin has very important use in the ICU, but it is often overused. Because of its virtually universal activity against gram-positive organisms, it is a mainstay of empiric therapy in the ICU. Its overuse, however, leads to the selection of resistant organisms. The mechanism of action is inhibition of cell-wall synthesis. Vancomycin binds to a peptide precursor of the cell wall, preventing the synthesis of peptidoglycan. 70 158 The Intensive Care Manual ch06.qxd 11/7/01 4:13 PM Page 158 Vancomycin is cleared from the body almost entirely through glomerular filtration. A dose adjustment is required in patients with renal failure, and peri- toneal dialysis and hemodialysis do not clear the drug. The major reason to monitor drug levels is to assure, in the critically ill patient, that sufficient levels are maintained. Peak-and-trough drug concentrations should be measured for patients with renal failure, those concomitantly on aminoglycosides, and critically ill patients far above or below their ideal body weight. 71 Gram-positive aerobic and anaerobic organisms are covered by vancomycin, including MRSA and Corynebacterium, Bacillus, and Clostridium species. It is most useful in the ICU for the treatment of serious infections with bacteria that are resistant to all other drugs, such as some strains of S. aureus, enterococci, coagulase-negative staphylococci, and Corynebacterium species. Because S. aureus is such a prevalent pathogen in the ICU, vancomycin is used empirically in hospitals with a high incidence of MRSA. However, in spite of its spectrum, it is not as effective against MSSA as oxacillin or cefazolin. Furthermore, it is not as effective against penicillin-sensitive bacteria as any of the penicillins, so its use should be restricted to those gram-positive organisms that are resistant to other antibiotics. The “red man syndrome” is pruritis, erythema, angioedema, and hypotension, caused by nonimmunologic release of histamine. The incidence is decreased by slow infusion of vancomycin (over 60 minutes). It is unclear whether vancomycin causes ototoxicity and nephrotoxicity or simply potentiates the ability of other drugs to do this. Uncommon adverse effects include drug fever, rash, agranulocytosis with high cumulative doses, and thrombophlebitis related to the infusion. Aminoglycosides The aminoglycosides remain an important drug in the ICU because of its broad gram-negative coverage and the need to empirically treat for Pseudomonas species infection with two drugs. They are bacteriocidal by binding to the 30S subunit of ribosomes, preventing protein synthesis. This requires energy- dependent transport of the drug across the outer bacterial membrane. 72 Most of the drug is excreted by glomerular filtration. Dose must therefore be adjusted in patients with renal failure. Approximately half of the serum level of aminoglycosides is cleared effectively with hemodialysis. Therefore, aminoglycosides should be administered after dialysis sessions. In traditional administration every 8 hours, toxicity has been associated with high trough concentrations in the blood. However, this may reflect the fact that renal tissue has become saturated and serum levels increase just before the creatinine level begins to rise, rather than just high trough concentrations “cause” renal failure. The concentration of aminoglycoside in the blood is altered by many variables, including age, sepsis, ascites, burns, fluid status, and renal function. 73 Most patients in the ICU have at least one of these confounding factors, and the volume of distribution is likely to change with the course of illness. This is why we advocate the use of traditional 6 / Infectious Disease 159 ch06.qxd 11/7/01 4:13 PM Page 159 dosing with regular monitoring of concentration of the drug in the blood in the ICU. The use of once-daily dosing regimen has the potential for increasing toxicity, even though in a general medical population the toxicity has been proven equal to traditional dosing. Aminoglycosides are effective against most gram-negative anaerobes, including Klebsiella, Pseudomonas, Acinetobacter, and Serratia species. There is activity against coagulase-negative staphylococci. Aminoglycosides may be used synergis- tically with beta-lactam antibiotics against enterococci, group A and B streptococci, and S. viridans. Aminoglycosides are a mainstay in the empiric treatment of ICU-related infections, such as ventilator-associated pneumonia, sinusitis, sepsis of unknown cause, and gram-negative UTI. The most common side effects of treatment are nephrotoxicity, ototoxicity, and neuromuscular blockade. Nephrotoxicity is a result of binding to receptors on the proximal tubular cells; it usually manifests 4 to 7 days after initiation of drug therapy and is almost always reversible after discontinuation of therapy. Nephrotoxicity usually produces a nonoliguric decrease in creatinine clearance and is potentiatied by volume depletion, age, and co-administration of vancomycin, amphotericin B, or furosemide. 74 Ototoxicity and vestibular toxicity result from accumulation of drug or metabolite in hair cells of the organ of Corti or ampullar cristae. Risks include loud ambient noise, duration of therapy, high trough concentrations in the blood, and concomitant administration of vancomycin or loop diuretics. Neuromuscular blockade is associated with rapid increase of drug concentration. With administration of aminoglycoside over at least 30 minutes, this adverse effect is rare. Fluoroquinolones The development of new agents in the fluoroquinolone class has increased the importance of this drug class in the treatment of infections in the ICU. There is potential for misuse, however, which may lead to the emergence of resistance. Quinolones bind to topoisomerase II (an enzyme found only in bacteria), which inhibits the supercoiling of DNA. There are multiple excretion pathways for the quinolones. The doses are generally not adjusted for hepatic failure, and those agents that are predominantly renally excreted are only dose-adjusted for severe renal impairment (ofloxacin, lomefloxacin). None of the agents is effectively cleared with hemodialysis. 75 The fluoroquinolones are generally safe, with few side effects. Some patients experience nausea, vomiting, diarrhea, headache, or dizziness. Arthropathy has been found in dog models, and this is the reason that fluoroquinolones are not approved for use in children. Arthropathy is a rare finding in adults. Hepatotoxi- city has also occurred in treatment with quinolone agents. CIPROFLOXACIN Ciprofloxacin has excellent activity against the Enterobacteri- acea, including Pseudomonas species. It is not an effective agent for community- acquired pneumonia, because of the lack of activity against S. pneumoniae. In the 160 The Intensive Care Manual ch06.qxd 11/7/01 4:13 PM Page 160 ICU, it is well-suited to treatment of gram-negative UTI, gram-negative sinusitis, or as part of an empiric regimen for VAP-related infection. Imipenem Imipenem is a beta-lactam antibiotic with an extended spectrum of activity. It is useful in the treatment of life-threatening infections in the ICU. The mechanism of bacterial killing is attachment to penicillin-binding proteins. Its molecular size allows entry into the periplasmic space of gram-negative bacteria, and its struc- ture gives it resistance to most beta-lactamases. 76 The drug is renally cleared and dose must be adjusted for severe renal impairment. Additional doses must be given after hemodialysis. The most common adverse effects are nausea, vomiting, and diarrhea. There is a spectrum of possible allergic reactions, as there are with other beta-lactam antibiotics. There is a risk of seizure that is greater with higher dosing and in patients with underlying neu- rologic disease. Before the introduction of newer generation fluoroquinolones, imipenem was the antibiotic with the broadest spectrum available, because of its affinity for multiple penicillin-binding proteins found in different species of bacteria. Anaer- obic organisms are very susceptible, with the exception of C. difficile. Imipenem is ineffective against MRSA and Enterococcus faecium. It has excellent activity against the important gram-negative pathogens in the ICU, including Pseudo- monas species, although resistance quickly develops if the agent is not used in combination with another antipseudomonal drug. Imipenem is generally reserved as an alternative drug in severe infections. Its value is greatest for infections in which first-line therapy has failed or against bacteria that are resistant to other agents. It may be used as an alternative in the empiric treatment of neutropenic fever, VAP infection, sinusitis, and sepsis of unknown cause. Aztreonam Aztreonam is a monobactam antibiotic with an affinity for the penicillin-binding protein 3, found exclusively in gram-negative bacteria, which accounts for the drug’s spectrum of activity. It is useful as an alternative to aminoglycosides. Aztreonam is a very safe drug. The most common side effects are local reactions, rash, diarrhea, nausea, and vomiting. 77 It is active against most gram- negative ICU pathogens, including Pseudomonas species, but with the exception of Acinetobacter species. Fluconazole Fluconazole is a useful antifungal agent in the ICU. The mechanism of action is interference with synthesis and permeability of fungal cell membranes. 78 The en- zymatic conversion of lanosterol to ergosterol, a major component of most fungal membranes, is inhibited. The most common use in critical care is treatment of candidiasis. There may be treatment failures against C. krusei or C. glabrata. 6 / Infectious Disease 161 ch06.qxd 11/7/01 4:13 PM Page 161 Fluconazole has excellent bioavailability when taken orally and should only be used intravenously when there is impairment of gut absorption. Most of the drug is excreted by the kidneys, and dose adjustment is required in patients with renal failure. Fluconazole is safe and well-tolerated. Most commonly, patients experience GI distress. There may be headache or mild elevation of transaminase level. Fluconazole increases the plasma concentration of theophylline, warfarin, cy- closporine, phenytoin, zidovudine, and oral hypoglycemics when used in combination. Amphotericin B Amphotericin B has traditionally been the first-line agent for most serious fungal infection, despite its considerable toxicity. It binds to ergosterol in the cell membranes of fungi, which alters permeability, allowing cellular contents to leak out and resulting in cell death. Virtually all fungi that cause disease are susceptible to amphotericin B. Toxicity occurs acutely with infusion or chronically with cumulative doses. The acute reactions include fever, chills, rigors, malaise, nausea, vomiting, headache, hypertension, and hypotension. Premedication with 400 to 600 mg of ibuprofen or with aspirin, acetaminophen, diphenhydramine, meperidine, or hydrocortisone may relieve these effects in some patients. Nephrotoxicity is the most serious chronic effect. The mechanism is not well understood. Be- tween 20% and 30% of patients receiving the drug experience a rise in serum creatinine level. Renal failure is almost always reversible with discontinuation of the drug. There is a protective effect of sodium administration before infusion of amphotericin B. Most patients receiving the drug require supplementation of potassium and magnesium. Other chronic effects include anemia, CNS disturbances (including delirium), depression, tremors, vomiting, and blurred vision. 79 The half-life of amphotericin B is extremely long, and serum concentrations are not altered significantly in hepatic or renal failure. Clearance is unchanged with dialysis. The liposomal or lipid complex form is usually substituted in patients with renal failure. However, experience indicates that creatinine levels often peak at 3.0 g/dL, even when standard amphotericin B therapy is maintained, and renal failure usually reverses when therapy is discontinued. Three alternate formulations of amphotericin B are currently available for use: amphotericin B lipid complex (ABLC), amphotericin B cholesteryl sulfate complex (ABCD), and liposomal amphotericin B. Each has proven less nephro- toxic compared with amphotericin B deoxycholate. Because of the enormous difference in cost compared with amphotericin B deoxycholate, the alternate formulations are generally reserved for patients with renal insufficiency before treatment, patients in whom acute renal failure develops while receiving amphotericin B deoxycholate, and patients in whom treatment fails with the traditional agent. 162 The Intensive Care Manual ch06.qxd 11/7/01 4:13 PM Page 162 [...]... post-HD 1 .5 3 g q6–8h 1 .5 3 g q12h 1 .5 3 g q24h 2. 25 g q6h 2. 25 g q8h 2. 25 g q8h plus 0. 75 g post-HD 0 .5 1 g q12h 0 .5 1 g q24–48h 0. 75 1 .5 g q12h 0. 75 g 24h May use supplemental dose post-HD 50 0 mg q24h (not meningitis) 1–2 g q24h 0 .5 1 g q24h 0. 25 0 .5 g q24h Repeat dose post-HD (continued) Penicillins Ampicillin 1 g q4–6ha 1 .5 g q4hb Nafcillin Piperacillin 1 g q4hc 1 .5 2 g q4hb 3–4 g q4–6h Ampicillin-sulbactam... for the use of antimicrobial agents in neutropenic patients with unexplained fever Clin Infect Dis 1997; 25: 551 57 3 51 Mulinde J, Joshi M The diagnostic and therapeutic approach to lower respiratory tract infections in the neutropenic patient J Antimicrob Chemother 1998;41(suppl D) :51 55 52 De Palo VA, Millstein BH, Mayo PH, et al Outcome of intensive care for patients with HIV infection Chest 19 95; 107 :50 6 51 0... g q8–12ha 2 g q8hb Cr Cl: 10 50 < 10 HD 50 0 mg q24–48h 50 0 mg q48–96h 1 g/week Ciprofloxacin 400 mg q12h Levofloxacin 50 0 mg q24h Cr Cl: 30 50 5 29 HD Cr Cl: 10 50 < 10 HD Trovafloxacin 200–300 mg q24h 200–400 mg q12h 200–400 mg q18h 200 mg q12h 250 mg q24h 1 25 250 mg q24h 1 25 mg q24h No change Cr Cl: 40–90 20–40 < 20 HD Cr Cl: 51 –90 10 50 < 10 HD q24h q48–72h Re-dose q5–7d 60–90% q8–12h 30–70% q12h... 19 95; 107 :50 6 51 0 53 Lazard T, Retel O, Guidet B, et al AIDS in a medical ICU: Immediate prognosis and long-term survival JAMA 1996;276( 15) :1240–12 45 54 Casalino E, Mendoza-Sassi G, Wolff M, et al Predictors of short- and long-term survival in HIV-infected patients admitted to the ICU Chest 1998;113:421–429 55 Bartlett JG 1998 medical management of HIV infection Johns Hopkins University, Department... 168 The Intensive Care Manual 58 Fishman JA, Rubin RH Infection in organ-transplant recipients N Engl J Med 1998;338(24):1741–1 751 59 Hospital Infections Program Intensive Care Antimicrobial Resistance Epidemiology (ICARE), 1998 www.sph.emory.edu/ICARE/ 60 Shlaes DM, Gerding DN, John JF Society for Healthcare Epidemiology of America and Infectious Diseases Society of American Joint Committee on the. .. right coronary artery The sinus node is heavily innervated by both sympathetic and parasympathetic fibers Parasympathetic stimulation reduces the rate of depolarization of the pacemaker cells in the sinus node and thereby slows the sinus rate Conversely, sympathetic stimulation increases the rate of depolarization of the pacemaker cells and causes an increase in the sinus rate The sinus rate in an individual... supply from the AV nodal artery, which in the majority (more than 90%) of cases arises from the right coronary artery Similarly to the sinus node, both sympathetic and parasympathetic nerves heavily innervate the AV node Conduction of the impulse from the sinus node through the AV node is represented on the surface ECG as the PR interval Most of the PR interval is a result of conduction through the AV node,... Carbohydrates Fats 25 kcal/kg/day 1.2–2.0 g/kg/day 100 15 25 ≈ 18 75 kcal/day 93. 75 g/day (3 75 kcal/day)b 50 % of calories 30% of calories 30– 65 15 30 2 35 g/day (940 kcal/day) 62 g/day (55 8 kcal/day) a % of Total Calories Micronutrients (vitamins, minerals, and trace elements) should be provided to meet needs and are available in a variety of combination preparations b Based on 1. 25 g/kg/day ch07.qxd... of BAL data on the therapy and outcome of ventilator-associated pneumonia Chest 1997;111:676–6 85 26 Kollef MH, Ward S The influence of mini-BAL cultures on patient outcomes Chest 1998;113:412–420 27 Alvarez-Lerma F and the ICU-Acquired Pneumonia Study Group Modification of empiric antibiotic treatment in patients with pneumonia acquired in the ICU Intens Care Med 1996;22:387–394 28 The choice of antibacterial... Baltimore, MD, 1998 56 Henson DL, Chu SY, Farizo KM, et al Distribution of CD4+ T lymphocytes at diagnosis of AIDS: Defining and other HIV-Related Illness Arch Intern Med 19 95; 155 : 153 7– 154 2 57 Stroud L, Srivastava P, Culver D, et al Nosocomial infections in HIV-infected patients: Preliminary results from a multicenter surveillance system (1989–19 95) Infect Control Hosp Epidemiol 1997;18:479–4 85 ch06.qxd 11/7/01 . post-HD Ampicillin-sulbactam 1 .5 3 g q6h Cr Cl: 30 50 1 .5 3 g q6–8h 15 29 1 .5 3 g q12h 5 14 1 .5 3 g q24h Piperacillin-tazobactam 3.3 75 g q6h Cr Cl: 20–40 2. 25 g q6h 4 .5 g q6h d < 20 2. 25 g. cell-wall synthesis. Vancomycin binds to a peptide precursor of the cell wall, preventing the synthesis of peptidoglycan. 70 158 The Intensive Care Manual ch06.qxd 11/7/01 4:13 PM Page 158 Vancomycin. q8h HD 2. 25 g q8h plus 0. 75 g post-HD Cephalosporins Cefazolin 0 .5 1 g q8h Cr Cl: 10–49 0 .5 1 g q12h < 10 0 .5 1 g q24–48h Cefuroxime 0. 75 1 .5 g q8h Cr Cl: 10–29 0. 75 1 .5 g q12h < 10 0. 75 g 24h HD

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