Anti-Infective Therapy

Anti-Infective Therapy

Despite dire warnings that we are approaching the end of the antibiotic era, the incidence of antibiotic-resistant bacteria continues to rise. The proportions of penicillin-resistant Streptococcus pneumoniae, hospital-acquired methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus strains continue to increase. Community-acquired methicillin-resistant Staphylococcus aureus is now common throughout the world. Multiresistant Acinetobacter and Pseudomonas are everyday realities in many of our hospitals. The press is now warning the lay public of the existence of “dirty hospitals.” As never before, it is critical that health care providers understand the principles of proper anti-infective therapy and use anti-infective agents judiciously. These agents need to be reserved for treatable infections — not used to calm the …

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Antibiotic Drugs and Antibiotic Resistance

Genetic Modifications Leading To Antimicrobial Resistance To understand why antibiotics must be used judiciously, the physician needs to understand how bacteria are able to adapt to their environment. Point mutations can develop in the Deoxyribonucleic acid of bacteria as they replicate. These mutations occur in the natural environment, but are of no survival advantage unless the bacteria are placed under selective pressures. In the case of a mutation that renders a bacterium resistant to a specific antibiotic, exposure to the specific antibiotic allows the bacterial clone that possesses the antibiotic resistance mutation to grow, while bacteria without the mutation die and no longer compete for nutrients. Thus the resistant strain becomes …

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Poliovirus vaccines

Two types of trivalent poliovirus vaccines are currently licensed for distribution in the United States: an enhanced inactivated vaccine and a live attenuated, oral vaccine. inactivated vaccine is the recommended vaccine for the primary series and booster dose for children in the United States, whereas oral vaccine is recommended in areas of the world that have circulating poliovirus. inactivated vaccine is given to children aged 2, 4, and 6 to 18 months and 4 to 6 years. Primary poliomyelitis immunization is recommended for all children and young adults up to age 18 years. Allergies to any component of inactivated vaccine, including streptomycin, polymixin B, and neomycin, are contraindications to vaccine use. …

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Anti-Infective Agent Dosing

The characteristics that need to be considered when administering antibiotics include absorption (when dealing with oral antibiotics), volume of distribution, metabolism, and excretion. These factors determine the dose of each drug and the time interval of administration. To effectively clear a bacterial infection, serum levels of the antibiotic need to be maintained above the minimum inhibitory concentration for a significant period. For each pathogen, the minimum inhibitory concentration is determined by serially diluting the antibiotic into liquid medium containing 104 bacteria per millihter. Inoculated tubes are incubated overnight until broth without added antibiotic has become cloudy or turbid as a result of bacterial growth. The lowest concentration of antibiotic that prevents …

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Specific Anti-Infective Agents

Antibiotics Before prescribing a specific antibiotic, clinicians should be able to answer these questions: •  How does the antibiotic kill or inhibit bacterial growth? •  What are the antibiotic’s toxicities and how should they be monitored? •  How is the drug metabolized, and what are the dosing recommendations? Does the dosing schedule need to be modified in patients with renal dysfunction? •  What are the indications for using each specific antibiotic? •  How broad is the antibiotic’s antimicrobial spectrum? •  How much does the antibiotic cost? Clinicians should be familiar with the general classes of antibiotics, their mechanisms of action, and their major toxicities. The differences between the specific antibiotics in …

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Antifungal Agents

Fungi are eukaryotes, and they share many of the structural and metabolic characteristics of human cells. As a result, designing agents that affect fungi without harming human cells has proved difficult. One major difference between the two cell types is the primary sterol building block used to form the plasma membrane. The fungal plasma membrane consists of ergosterols; the major sterol component of the human plasma membrane is cholesterol. This difference has been exploited in the development of two classes of drugs. The polyenes act by binding to ergosterol and disrupting the fungal membrane. These agents are fungicidal. The azoles inhibit ergosterol synthesis, and lowered ergosterol levels results in fungal membrane …

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