Antimicrobials initial

Oxazolidinones are a new class of synthetic antimicrobial agents, which have activity against many important pathogens, including methicillin-resistant Staphylococcus aureus and others. Oxazolidinones (e.g. linezolid or eperezolid) inhibit bacterial protein synthesis by inhibiting the formation of the 70S initiation complex by binding to the 50S ribosomal subunit close to the interface with the 3OS subunit. 

Lambert M, S Kremer, H Anke (1995) Antimicrobial, phytotoxic, nematicidal, cytotoxic, and mutagenic activities of 1-hydroxypyrene, the initial metabolite in pyrene metabolism by the basidiomycete Crinipellis stipitaria. Bull Environ Contam Toxicol 55 251-257. 

Inadequate diagnosis resulting in poor initial antimicrobial selection, poor source control, or the development of a new infection with a resistant organism is a relatively common cause of antimicrobial failure. 

Most initial antimicrobial therapy is empirical because cultures usually have not had sufficient time to identify a pathogen. Empirical therapy should be based on patient- and antimicrobial-specific factors such as the anatomic location of the infection, the likely pathogens associated with the presentation, the potential for adverse effects in a given patient, and the antimicrobial spectrum of activity. Prompt initiation of appropriate therapy is paramount in hospitalized patients who are critically ill. Patients who receive initial antimicrobial therapy that provides coverage against the causative pathogen survive at twice the rate of patients who do not receive adequate therapy initially.8... 

Empirical selection of antimicrobial spectrum of activity should be related to the severity of the illness. Generally, acutely ill patients may require broader-spectrum antimicrobial coverage, whereas less ill patients may be managed initially with narrow-spectrum therapy. While a detailed description of antimicrobial pathogen- specific spectrum of activity is beyond the scope of this chapter, this information can be obtained readily from a number of sources.9,10... 

Renal and/or hepatic function should be considered in every patient prior to initiation of antimicrobial therapy. In general, most antimicrobials undergo renal elimination and... 

After selection and initiation of antimicrobial regimen, there are a number of additional patient care and monitoring considerations that should be addressed to improve the likelihood of a successful outcome. Patient education, deescalation of antimicrobial therapy based on culture results, monitoring for clinical response and adverse effects, and appropriate duration of therapy are important. 

Ideally, lumbar puncture to obtain cerebrospinal fluid (CSF) for direct examination and laboratory analysis, as well as blood cultures and other relevant cultures, should be obtained before initiation of antimicrobial therapy. However, initiation of antimicrobial therapy should not be delayed if a pretreatment lumbar puncture cannot be performed. 

Prompt initiation of intravenous high-dose cidal antimicrobial therapy directed at the most likely pathogen (s) is essential due to the high morbidity and mortality associated with CNS infections parenteral (intravenous) therapy is administered for the full course of therapy for CNS infections to ensure adequate CSF penetration throughout the course of treatment. 

A high index of suspicion should be maintained for patients at risk for CNS infections. Prompt recognition and diagnosis are essential so that antimicrobial therapy can be initiated as quickly as possible. A medical history (including risk factors for infection and history of possible recent exposures) and... 

Determine if the patient can undergo an immediate LP or if the LP should be delayed until a CNS mass lesion can be ruled out. If the LP is delayed, blood cultures should be drawn and appropriate empirical antimicrobial therapy initiated immediately. 

Resolution of signs and symptoms typically occurs within a few days to a week in most cases. Monitor the patient daily for febrile episodes, as well as other vital signs, with expected normal values within 2 to 3 days of initiating antimicrobial therapy.3 Persistent signs or symptoms could be indicative of inadequate treatment or development of resistance. 

Review available microbiologic cultures and sensitivity to assess whether the initial antimicrobial regimen needs to be tailored ... 

Patients with complicated typhoid fever (i.e., metastatic foci, ileal perforation, etc.) should receive parenteral therapy with ciprofloxacin 400 mg twice daily or ceftriaxone 2000 mg once daily. Antimicrobial therapy can be completed with an oral agent after initial control of the symptoms of typhoid fever. In persons with AIDS and a first episode of Salmonella bacteremia, a longer duration of antibiotic therapy (1-2 weeks of parenteral therapy followed by 4 weeks of oral fluoroquinolone) is recommended to prevent relapse of bacteremia. 

Cultures of secondary intraabdominal infection sites generally are not useful for directing antimicrobial therapy. Treatment generally is initiated on a presumptive or empirical basis. 

TABLE 74-3. Guidelines for Initial Antimicrobial Agents for Intraabdominal Infections... 

Whether diagnosed with primary or secondary peritonitis, monitor the patient for relief of symptoms. Once antimicrobials are initiated and the other important therapies described earlier are used, most patients should show improvement within 2 to 3 days. Successful antimicrobial therapy with resolution of infection will result in decreased pain, manifested as resolution of abdominal guarding and decreased use of pain medications over time. The patient should not appear in distress, with the exception of recognized discomfort and pain from incisions, drains, and a nasogastric tube. 

The initial antimicrobial regimen should conform to standard guidelines unless an appropriate justification for an alternative regimen is evident. With the first few doses of antimicrobial, assess the patient for hypersensitivity reactions or other acute intolerances. 

Based on culture and susceptibility data (if available), are there any changes that need to be made from your initial empiric antimicrobial selection (i.e., resistance to the regimen initially selected) ... 

Antimicrobial therapy should be modified based on culture and sensitivity data of appropriately collected specimens (Table 78-2).2 17 ls Typically, treatment is initiated with intravenous antimicrobials to ensure that therapeutic drug concentrations will... 

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