1. Description of the problem
Principles of antimicrobial therapy
In patients suspected of being infected, the following elements of management should always be considered but may not all necessarily apply in all cases:
Supportive care, e.g., treat shock, hypoxia.
Need for surgery – for diagnosis or therapy, e.g., drainage of abscess.
Community – is this contagious? What interventions are required to prevent spread within the community (ward, hospital, family, broader community)?
Prevention – e.g., immunization, antimicrobial chemoprophylaxis of contacts, care of vascular catheters.
This chapter addresses antimicrobial therapy.
The first set of decisions to be made:
Is an infection likely?
Where is it located? This usually provides the answer to the third and most important question:
What are the most likely causative organisms?
What are the likely antimicrobial susceptibilities of these organisms?
Initial management is empiric; to answer questions 3 and 4, one should use the following: (1) information from published studies of this infection; and (2) information from your specific unit.
Microbiologic information should be obtained from the patient to provide directed therapy. The most important principle in obtaining microbiological information is that specimens should be obtained from the site or presumed site of infection whenever possible. Blood cultures give information only about organisms in the blood.
The second decision to be made:
Given the answers to the first set of questions, what is the optimal agent to use?
This must take into account:
The necessary antimicrobial spectrum of the agent(s).
Will it reach the site of the infection?
Route of administration.
Cost (use the cheapest drug, other factors being equal).
The overriding principle is to use the narrowest spectrum agent possible for the clinical circumstance.
The susceptibilities of different bacteria to different antimicrobial agents are fairly predictable. However these susceptibilities vary over time and place. Therefore, it is important to know the susceptibilities of specific organisms in your hospital and unit.
Table I indicates commonly encountered/important microbial agents in the intensive care unit, and their usual susceptibilities.
Table II lists the organisms causing different types of infections at different sites in different types of hosts and suggested empiric therapy (i.e. the initial therapy based on the clinical and epidemiological information, prior to the availability of microbiological information). Once or if a specific agent is identified, therapy should be tailored accordingly.
Table III lists the dosages, dosing intervals and routes of administration of antimicrobial agents by categories for children after the newborn period and for adults.
Table IV lists the major adverse effects of antimicrobial agents.
|Aminoglycosides||Ototoxicity (auditory and vestibular), nephrotoxicity, potentiation of neuromuscular blockade|
|Cephalosporins||Allergy, rashes, Coombs positivity, prolonged PT/PTT, thrombocytopenia|
|Ceftriaxone||Gallbladder sludge; displacement of bilirubin from albumen;
do not administer with iv calcium
|Cefepime||Allergy, diarrhea, neurotoxicity|
|Cefazolin||Allergy, elevated transaminases, decreased renal function, neutropenia, thrombocytopenia|
|Clindamycin||Diarrhea, rash, potentiation of neuromuscular blockade|
|Daptomycin||Myositis, eosinophilic pneumonia, peripheral neuropathy|
|Fluoroquinolones||Dizziness, abdominal pain, photosensitivity, arthralgia, tendon rupture, interactions (especially Q-T interval prolongation; mental status changes (especially with non-steroidal drugs)|
|Linezolid||Myelosuppression, peripheral and optic neuropathy (long-term usage), interactions, especially with serotoninergic agents|
|Macrolides||Interactions (especially prolonged Q-Tc), gastrointestinal|
|Erythromycin||Upper abdominal discomfort, nausea/vomiting, diarrhea, cholestasis (estolate salt), dysrhythmia (iv), pyloric stenosis (neonate)|
|Metronidazole||Metallic taste; disulfiram reaction; encephalopathy (prolonged usage)|
|Penicillins (most)||Allergy, rashes, seizures (high dosages), interstitial nephritis, thrombocytopenia, neutropenia, eosinophilia, Coombs positivity, sodium excess|
|Nafcillin||Interaction with warfarin, increased transaminases|
|Piperacillin/tazobactam||Coagulopathy (associated with renal failure)|
|Polymyxin/Colistin||Nephrotoxicity, neurotoxicity, neuromuscular blockade|
|Rifampin||Body fluid discoloration, interactions (very important), hepatotoxicity, thrombocytopenia, and “flu-like” symptoms when taken intermittently|
|Tetracyclines||Diarrhea, bacterial overgrowth, photosensitivity, pseudotumor cerebri, hepatotoxicity, nephrotoxicity, vestibular disturbance (minocycline), dental staining (you must be alive to develop this!)|
|Trim/sulfa*||Allergy, Stevens-Johnson syndrome and other skin reactions, crystalluria, nephrotoxicity, bone-marrow suppression, hemolysis – with and without G6PD deficiency, hyperkalemia, bilirubin displacement (newborn)|
|Vancomycin||Ototoxicity, nephrotoxicity, anaphylactoid reactions (“red man syndrome”)|
|Isoniazid (INH)||Hepatotoxicity, peripheral neuropathy, hypersensitivity|
|Pyrazinamide||Hepatotoxicity, hyperuricemia, arthralgia|
|Streptomycin||Ototoxicity (hearing and vestibular), nephrotoxicity|
|Ethionamide||Gastrointestinal, hepatotoxicity, neurotoxicity, hypothyroidism|
|Amphotericin B||Nephrotoxicity, hypokalemia, fever and chills, hypotension|
|Azoles||Nausea, vomiting, drug-drug interactions, prolonged Q-Tc, hepatotoxicity|
|Voriconazole||Hepatotoxicity, interactions, visual disturbance (transient after dose), fluorosis (prolonged usage)|
|Posaconazole||Adrenal insufficiency, nephrotoxicity, prolonged Q-Tc|
|Itraconazole||Nausea, vomiting, diarrhea, rash|
|Echinocandins||Relatively free of adverse effects|
|Micafungin||Drug-drug interaction (sirolimus, nifedipine)|
|Acyclovir||Neurotoxicity, nephrotoxicity (crystalluria), neutropenia, phlebitis (iv)|
|Foscarnet||Nephrotoxicity, electrolyte disturbances, especially of ionized calcium, magnesium and phosphorus, neurotoxicity, neutropenia|
|Ganciclovir||Neutropenia, thrombocytopenia, anemia, upper intestinal symptoms, mental status changes|
|Oseltamivir||Nausea, vomiting, diarrhea, skin reactions, behavioral changes|
|Antiretrovirals||Interactions (very important), nausea, diarrhea, severe hypersensitivity – affecting skin and viscera, hepatotoxicity, hyperlipidemia, fat maldistribution|
|Abacavir||Severe hypersensitivity (test for HLA-B*5701)|
|Atazanavir||Indirect hyperbilirubinemia, 1st degree heart block, rash, hyperglycemia, nephrolithiasis, hyperlipidemia|
|Darunavir||Rash, hepatotoxicity, hyperglycemia, hyperlipidemia|
|Dolutegravir||Hypersensitivity, insomnia, headache|
|Efavirenz||Rash, psychologic disturbances, hepatotoxicity, ? teratogenic|
|Emtricitabine||Skin discoloration, exacerbation of liver disease when discontinued in individuals with hepatitis B|
|Lamivudine||Lactic acidosis, fever, cough, exacerbation of liver disease when discontinued in individuals with hepatitis B|
|Nevirapine||Hepatotoxicity, severe hypersensitivity reactions|
|Raltegravir||Rash, dizziness, insomnia, fever, rhabdomyolysis|
|Tenofovir disoproxil fumarate||Nephrotoxicity, decreased mineral bone density|
|Zidovudine||Anemia, neutropenia, lactic acidosis, myopathy, lipoatrophy|
|Artemether- lumefantrine||Palpitations, arthralgia, myalgia, fatigue|
|Artesunate||Prolonged Q-Tc, dizziness, insomnia, hearing problems, anemia (3-4 weeks later)|
|Atovaquone/proguanil||Nausea, abdominal pain, headache, interactions, elevated transaminases|
|Chloroquine||Dizziness, nausea, vomiting, blurred vision, pruritus|
|Quinidine||Hypotension, dysrhythmias, including prolonged Q-Tc, diarrhea, interactions|
|Quinine||Cinchonism (tinnitus, visual disturbance, headache, nausea, abdominal pain), Hemolysis, deafness, photosensitivity IV: hypotension, hypoglycemia, dysrhythmias|
Trim/sulfa = trimethoprim/sulfamethoxazole
2. Emergency Management
Special considerations for nursing and allied health professionals.
What's the evidence?
Baltimore, RS, Gewitz, M, Baddour, LM. “Infective endocarditis in childhood: 2015 update. A scientific statement from the American Heart Association”. Circulation. vol. 132. 2015. pp. 1487-1515.
Green, M. “Introduction: Infections in solid organ transplantation”. Am J Transplant. vol. 13. 2013. pp. 3-8.
Fishman, JA. “Infection in Solid-Organ Transplant Recipients”. N Engl J Med. vol. 357. 2007. pp. 2601-14.
Jankelevich, S, Zeichner, SL, Read, JS. “Serious infections caused by typical bacteria”. Handbook of Pediatric HIV Care. 2006. pp. 653-73.
Lehrnbecher, T, Phillips, R, Alexander, S. “Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation”. J Clin Oncol. vol. 20. 2012. pp. 4427-4438.
Freifeld, AG, Bow, EJ, Sepkowitz, KA. “Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America”. Clin Infect Dis. vol. 52. 2011. pp. e56-e93.
Long, SS, Pickering, LK, Prober, CG. Principles and Practice of Pediatric Infectious Diseases. 2012.
Bennett, JE, Dolin, R, Blaser, MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 2015.
Red Book 2015 Report of the Committee on Infectious Diseases.
Bradley, JS, Nelson, JD. “Nelson's Pocket Book of Pediatric Antimicrobial Therapy”. 2016.
Gilbert, DN, Chambers, HF, Eliopoulos, GM, Saag, MS. The Sanford Guide to Antimicrobial Therapy 2015.
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