Antimicrobial Regimen Selection Upon completion of the chapter, the reader will be able to: 1. Recognize that antimicrobial resistance is an inevitable consequence of antimicrobial therapy. 2. Describe how antimicrobials differ from other drug classes in terms of their effects on individual patients as well as on society as a whole. 3. Identify two guiding principles to consider when treating patients with antimicrobials, and apply these principles in patient care. 4. Differentiate between microbial colonization and infection based on patient history, physical examination, and laboratory and culture results. 5. Evaluate and apply at least six major drug- specific considerations when selecting antimicrobial therapy. 6. Evaluate and apply at least seven major patient-specific considerations when selecting antimicrobial therapy. 7. Select empirical antimicrobial therapy based on spectrum-of-activity considerations that provide a measured response proportional to the severity of illness. Provide a rationale for why a measured response in antimicrobial selection is appropriate. 8. Identify and apply five major principles of patient education and monitoring response to antimicrobial therapy.
Transcript
Antimicrobial RegimenSelection
Upon completion of the chapter, the reader will be able to:1. Recognize that antimicrobial resistance is an inevitable consequence of antimicrobial therapy.2. Describe how antimicrobials differ from other drug classes in terms of their effects on individualpatients as well as on society as a whole.3. Identify two guiding principles to consider when treating patients with antimicrobials, and applythese principles in patient care.4. Differentiate between microbial colonization and infection based on patient history, physicalexamination, and laboratory and culture results.5. Evaluate and apply at least six major drug-specific considerations when selecting antimicrobialtherapy.6. Evaluate and apply at least seven major patient-specific considerations when selectingantimicrobial therapy.7. Select empirical antimicrobial therapy based on spectrum-of-activity considerations that provide ameasured response proportional to the severity of illness. Provide a rationale for why a measuredresponse in antimicrobial selection is appropriate.8. Identify and apply five major principles of patient education and monitoring response toantimicrobial therapy.9. Identify two common causes of patients failing to improve while on antimicrobials
The discovery of antimicrobials is among the greatest
medical achievements of the 20th century. Prior tothe antimicrobial era, patients who contracted commoninfectious diseases developed significant morbidity or
perished. The discovery of penicillin in 1927, followed by thesubsequent discovery of other antimicrobials, contributed toa significant decline in infectious disease–related mortalityduring the next five decades. However, since 1980, infectiousdisease–related mortality in the United States has increased,in part owing to increases in antimicrobial resistance.The discovery of virtually every new class of antimicrobialshas occurred in response to the development of bacterialresistance and loss of clinical effectiveness of existingantimicrobials. 1 An inevitable consequence of exposingmicrobes to antimicrobials is that some organisms will developresistance to the antimicrobial. Today, there are dozens ofantimicrobial classes and hundreds of antimicrobials availablefor clinical use. However, in many cases, differences inmechanisms of action between antimicrobials are minor,and the microbiologic properties of the agents are similar.2 Antimicrobials are different from other classes of pharmaceuticalsbecause they exert their action on bacteria infectingthe host as opposed to acting directly on the host. Because useof an antimicrobial in one patient affects not only that patientbut also other patients if they become infected with resistantbacteria, correct selection, use, and monitoring of clinicalresponse are paramount.3 There are two guiding principles to consider whentreating patients with antimicrobials: (a) make the correctdiagnosis and (b) do no harm! Patients with infectionsfrequently present with signs and symptoms that arenonspecific for infection and may be confused with othernoninfectious disease. Not only is it important to determinewhether a disease process is of infectious origin, butit is also important to determine the specific causativepathogen of the infection. Antimicrobials vary in their
spectrum of activity, the ability to inhibit or kill differentspecies of bacteria. Antimicrobials that kill many differentspecies of bacteria are called broad-spectrum antimicrobials,whereas antimicrobials that kill only a few species ofbacteria are called narrow-spectrum antimicrobials. Onemight argue that treating everybody with broad antimicrobialantimicrobials will increase the likelihood that apatient will get better even without knowing the bacteriacausing infection. However, counter to this argument isthe principle of “Do no harm!” Broad antimicrobial coveragedoes increase the likelihood of empirically killinga causative pathogen; unfortunately, the development ofsecondary infections can be caused by selection of antimicrobial-resistant nontargeted pathogens. In addition,adverse events are thought to complicate up to 10% of allantimicrobial therapy, and for select agents, the adverseeventrates are similar to high-risk medications such aswarfarin, digoxin, or insulin.1 Therefore, the overall goalof antimicrobial therapy should be to cure the patient’sinfection; limit harm by minimizing patient risk foradverse effects, including secondary infections; and limitsocietal risk from antimicrobial-resistant bacteria.
EPIDEMIOLOGY AND ETIOLOGYInfectious disease–related illnesses, particularly respiratorytract infections, are among the most common reasons patientsseek medical care.2 Antimicrobial prescribing in the pasthas been associated with inappropriate use of antimicrobialagents. During the late 1990s/early 2000s, many organizationsinitiated campaigns to promote appropriate antimicrobialuse. Recent trends in prescribing suggest a modest reductionin antimicrobial use for these infections, suggestingan increased recognition of the negative consequences of
antimicrobial use.4 Prescribing of antimicrobials in hospitalizedpatients is also common, as up to one-half of all patientsreceive at least one antimicrobial during hospitalization.In 2002, the estimated number of nosocomial infections was1.8 million, with an estimated 99,000 deaths.5 In 2009, the CDCreported 25,000 fewer central line–associated bloodstreaminfections than in 2001, a 58% reduction.6 Nosocomial infectionstend be associated with antimicrobial-resistant strainsof bacteria. However, there has been a shift in the etiology ofsome community-acquired infections. Increasingly, infectionscaused by antimicrobial-resistant pathogens, traditionallynosocomial in origin, are being identified in ambulatory caresettings. Reasons for this change include an aging populace,improvement in the management of chronic comorbid conditionsincluding immunosuppressive conditions, and increasesin outpatient management of more debilitated patients. Themajority of infections caused by antimicrobial-resistant pathogensin the ambulatory care setting occur in patients who havehad recent exposure to some aspect of the healthcare systemand are therefore defined as healthcare–associated infections.The converging bacterial etiologies and increasing resistancein all healthcare environments emphasize the need to “makethe diagnosis.”
PATHOPHYSIOLOGYNormal Flora and Endogenous Infection
Many areas of the human body are colonized with bacteria—this is known as normal flora. Infections often arise fromone’s own normal flora (also called an endogenous infection).Endogenous infection may occur when there are alterationsin the normal flora (e.g., recent antimicrobial use mayallow for overgrowth of other normal flora) or disruption ofhost defenses (e.g., a break or entry in the skin). Knowingwhat organisms reside where can help to guide empirical antimicrobialtherapy (Fig. 69–1). In addition, it is beneficialto know what anatomic sites are normally sterile. Theseinclude the cerebrospinal fluid, blood, and urine.
Determining Colonization Versus Infection
Infection refers to the presence of bacteria that are causingdisease (e.g., the organisms are found in normally sterileanatomic sites or in nonsterile sites with signs/symptoms ofinfection). Colonization refers to the presence of bacteria thatare not causing disease. 4 Only bacteria that cause diseaseshould be targeted with antimicrobial therapy, and non–disease-producing colonizing flora should be left intact. Itis important to differentiate infection from colonizationbecause antimicrobial therapy targeting bacterial colonizationis inappropriate and may lead to the development ofresistant bacteria.Exogenously Acquired Bacterial InfectionsInfections acquired from an external source are referred to asexogenous infections. These infections may occur as a resultof human-to-human transmission, contact with exogenousbacterial populations in the environment, and animal contact.Resistant pathogens such as methicillin-resistant Staphylococcusaureus (MRSA) and vancomycin-resistant Enterococcusspp. (VRE) may colonize hospitalized patients or patientswho access the healthcare system frequently. It is key toknow which patients have acquired these organisms becausepatients generally become colonized prior to developinginfection, and colonized patients should be placed in isolation(per infection-control policies) to minimize transmission toother patients.Contrasting Bacterial Virulenceand ResistanceVirulence refers to the pathogenicity or disease severity producedby an organism. Many bacteria may produce toxins orpossess growth characteristics that contribute to their pathogenicity.
Some virulence factors allow the organism to avoidthe immune response of the host and cause significant disease.Virulence and resistance are different microbial characteristics.For example, Streptococcus pyogenes, a common cause ofskin infections, produces toxins that can cause severe disease,yet it is very susceptible to penicillin. Enterococcus faecium is a highly resistant organism but is frequently a colonizing florathat causes disease primarily in the immunocompromised.
CLINICAL PRESENTATIONAND DIAGNOSISPhysical ExaminationFindings on physical examination, along with the clinicalpresentation, can help to provide the anatomic location of theinfection. Once the anatomic site is identified, the most probablepathogens associated with disease can be determinedbased on likely endogenous or exogenous flora.Fever often accompanies infection and is defined as a risein body temperature above the normal 37C (98.6F). Oraland axillary temperatures may underestimate core temperatureby at least 0.6C (1F), whereas rectal temperatures bestapproximate core temperatures. Fever is a host response tobacterial toxins. However, bacterial infections are not thesole cause of fever. Fever also may be caused by other infections(e.g., fungal or viral), medications (e.g., penicillins,cephalosporins, salicylates, and phenytoin), trauma, or othermedical conditions (e.g., autoimmune disease, malignancy,pulmonary embolism, and hyperthyroidism). Some patientswith infections may present with hypothermia (e.g., patientswith overwhelming infection). Elderly patients may be afebrile,as may those with localized infections (e.g., urinary
tract infection).7 For others, fever may be the only indicationof infection. For example, neutropenic patients may not havethe ability to mount normal immune responses to infection(e.g., infiltrate on chest x-ray, pyuria on urinalysis, orerythema or induration around catheter site), and the onlyfinding may be fever.Imaging StudiesImaging studies also may help to identify anatomic localizationof the infection. These studies usually are performedin conjunction with other tests to establish or ruleout the presence of an infection. Radiographs are performedcommonly to establish the diagnosis of pneumonia,as well as to determine the severity of disease (single versusmultilobe involvement). Computed tomography (CT)scans are a type of x-ray that produces a three-dimensionalimage of the combination of soft tissue, bone, and bloodvessels. In contrast, magnetic resonance imaging (MRI)uses electromagnetic radio waves to produce two- or threedimensionalimages of soft tissue and blood vessels withless detail of bony structures. Nonmicrobiologic Laboratory StudiesCommon nonmicrobiological laboratory tests include thewhite blood cell count (WBC) and differential, erythrocytesedimentation rate (ESR), and determination of biomarkersC-reactive protein (CRP) or procalcitonin levels. In mostcases, the WBC count is elevated in response to infection,but it may be decreased owing to overwhelming or longstandinginfection. The differential is the percentage of eachtype of WBC (Table 69–1). In response to physiologic stress,neutrophils leave the bloodstream and enter the tissue to“fight” against the offending pathogens (i.e., leukocytosis).It is important to recognize that leukocytosis is nonspecificfor infection and may temporarily occur in response to noninfectious
conditions such as acute myocardial infarction.During an infection, immature neutrophils (e.g., bands) arereleased at an increased rate to help fight infection, leading towhat is known as a bandemia or left shift. Therefore, a WBCcount differential is key to determining whether an infectionis present. Some patients may present with a normal totalWBC with a left shift (e.g., the elderly). ESR and CRP are nonspecific markers of inflammation that increase as a resultof the acute-phase reactant response, which is a responseto inflammatory stimuli such as infection or tissue injury.These tests may be used as markers of infectious diseaseresponse because they are elevated when the disease isacutely active and usually fall in response to successful treatment.Clinicians may use these tests to monitor a patient’sresponse to therapy in osteomyelitis and infective endocarditis.These tests should not be used to diagnose infectionbecause they may be elevated in noninfectious inflammatoryconditions (e.g., rheumatoid arthritis, polymyalgia rheumatica,and temporal arteritis). In contrast, procalcitonin, aprohormone of calcitonin, is rapidly produced in response tobacterial infection. Procalcitonin serum levels in conjunctionwith clinical findings are increasingly being utilized to assessboth the need to initiate antibiotic therapy as well as determinewhen antibiotic therapy may be safely discontinued. Nonmicrobiologic Laboratory StudiesCommon nonmicrobiological laboratory tests include thewhite blood cell count (WBC) and differential, erythrocytesedimentation rate (ESR), and determination of biomarkersC-reactive protein (CRP) or procalcitonin levels. In mostcases, the WBC count is elevated in response to infection,but it may be decreased owing to overwhelming or longstandinginfection. The differential is the percentage of each
type of WBC (Table 69–1). In response to physiologic stress,neutrophils leave the bloodstream and enter the tissue to“fight” against the offending pathogens (i.e., leukocytosis).It is important to recognize that leukocytosis is nonspecificfor infection and may temporarily occur in response to noninfectiousconditions such as acute myocardial infarction.During an infection, immature neutrophils (e.g., bands) arereleased at an increased rate to help fight infection, leading towhat is known as a bandemia or left shift. Therefore, a WBCcount differential is key to determining whether an infectionis present. Some patients may present with a normal totalWBC with a left shift (e.g., the elderly). ESR and CRP are nonspecific markers of inflammation that increase as a resultof the acute-phase reactant response, which is a responseto inflammatory stimuli such as infection or tissue injury.These tests may be used as markers of infectious diseaseresponse because they are elevated when the disease isacutely active and usually fall in response to successful treatment.Clinicians may use these tests to monitor a patient’sresponse to therapy in osteomyelitis and infective endocarditis.These tests should not be used to diagnose infectionbecause they may be elevated in noninfectious inflammatoryconditions (e.g., rheumatoid arthritis, polymyalgia rheumatica,and temporal arteritis). In contrast, procalcitonin, aprohormone of calcitonin, is rapidly produced in response tobacterial infection. Procalcitonin serum levels in conjunctionwith clinical findings are increasingly being utilized to assessboth the need to initiate antibiotic therapy as well as determinewhen antibiotic therapy may be safely discontinued.
A full discussion of the role of procalcitonin in diagnosing
and treating disease is beyond the scope of this chapter.8,9
Microbiologic StudiesMicrobiologic studies that allow for direct examination of aspecimen (e.g., sputum, blood, or urine) also may aid in apresumptive diagnosis and give an indication of the characteristicsof the infecting organism. Generally, microbial culturesare obtained with a Gram stain of the cultured material.A Gram stain of collected specimens can give rapid informationthat can be applied immediately to patient care. AGram stain is performed to identify whether bacteria arepresent and to determine morphologic characteristics ofbacteria (e.g., gram-positive or gram-negative or shape—cocci, bacilli). Certain specimens do not stain well or at alland must be identified by alternative staining techniques(Mycoplasma spp., Legionella spp., Mycobacterium spp.).Figure 69–2 identifies bacterial pathogens as classified by Gram stain and morphologic characteristics. The presence ofWBCs on a Gram stain indicates inflammation and suggeststhat the identified bacteria are pathogenic. The Gram stainmay be useful in judging a sputum specimen’s adequacy. Forexample, the presence of epithelial cells on sputum Gramstain suggests that the specimen is either poorly collected orcontaminated. A poor specimen can give misleading informationregarding the underlying pathogen and is a waste oflaboratory personnel time and patient cost.Culture and susceptibility testing provides additionalinformation to the clinician to select appropriate therapy.Specimens are placed in or on culture media that providethe proper growth conditions. Once the bacteria grow onculture media, they can be identified through a variety ofbiochemical tests. Once a pathogen is identified, susceptibility
tests can be performed to various antimicrobial agents.The minimum inhibitory concentration (MIC) is a standardsusceptibility test. The MIC is the lowest concentration ofantimicrobial that inhibits visible bacterial growth afterapproximately 24 hours (Fig. 69–3). Breakpoint and MICvalues determine whether the organism is susceptible (S),intermediate (I), or resistant (R) to an antimicrobial. Thebreakpoint is the concentration of the antimicrobial that canbe achieved in the serum after a normal or standard doseof that antimicrobial. If the MIC is below the breakpoint,the organism is considered to be susceptible to that agent.If the MIC is above the breakpoint, the organism is saidto be resistant. Reported culture and susceptibility resultsmay not provide MIC values but generally report the S, I,and R results.5 In general, bacterial cultures should be obtained priorto initiating antimicrobial therapy in patients with a systemicinflammatory response, risk factors for antimicrobialresistance, or infections where diagnosis or antimicrobialsusceptibility is uncertain. The decision to collect a specimenfor culture depends on the sensitivity and specificity ofthe physical findings, diagnostic examination findings, andwhether or not the pathogens are readily predictable. Cultureand susceptibility testing usually is not warranted in a young,otherwise healthy woman who presents with signs and symptomsconsistent with a urinary tract infection (UTI) becausethe primary pathogen, Escherichia coli, is readily predictable.Cultures and susceptibility testing are routine for sterile-sitespecimens (e.g., blood and spinal fluid), as well as for materialpresumed to be infected (e.g., material obtained fromjoints and abscesses). Cultures need to be interpreted withcaution. Poor specimen collection technique and processingspeed can result in misleading information and inappropriate
use of antimicrobials.
TREATMENTGeneral Approach to Treatment, IncludingNonantimicrobial TreatmentWhile selection of antimicrobial therapy may be a majorconsideration in treating infectious diseases, it may not bethe only therapeutic intervention. Other important therapiesmay include adequate hydration, ventilatory support, andother supportive medications. In addition, antimicrobials areunlikely to be effective if the process or source that leads tothe infection is not controlled. Source control refers to this processand may involve removal of prosthetic materials such ascatheters and infected tissue or drainage of an abscess. Sourcecontrol considerations should be a fundamental component ofany infectious diseases treatment. It is also important to recognizethat there may be many different antimicrobial regimensthat may cure the patient. While the following therapy sectionsprovide factors to consider when selecting antimicrobial regimens,an excellent and more in-depth resource for selectingantimicrobial regimens for a variety of infectious diseases arethe Infectious Diseases Society of America Guidelines.10
Antimicrobial Considerationsin Selecting Therapy6 Drug-specific considerations in antimicrobial selectioninclude spectrum of activity, effects on nontargeted microbialflora, appropriate dose, pharmacokinetic and pharmacodynamicproperties, adverse-effect and drug-interaction profile,and cost (Table 69–2).
oral bioavailability include the salt formulation of the antimicrobial,the dosage form, and the stability of the drug in thegastrointestinal tract. Frequently, absorption may be affectedby gastrointestinal tract blood flow. All patients that manifestsystemic signs of infection such as hypotension or hypoperfusionshould receive intravenous antimicrobials to ensure drugdelivery. In almost all cases where patients have a functioninggastrointestinal tract and are not hypotensive, antimicrobialswith almost complete bioavailability (greater than 80%) suchas the fluoroquinolones, fluconazole, and linezolid may begiven orally. With antimicrobials with modest bioavailability(e.g., many β-lactams), the decision to choose an oral productwill depend more on the severity of the illness and theanatomic location of the infection. In sequestered infections,where higher systemic concentrations of antimicrobial maybe necessary to reach the infected source (e.g., meningitis) orfor antimicrobials with poor bioavailability, IV formulationsshould be used.Several points regarding how the antimicrobial distributesinto tissue are worth mentioning. First, only antimicrobialsnot bound to albumin are biologically active. Protein bindingis likely clinically irrelevant in antimicrobials with low orintermediate protein binding. However, highly protein-boundantimicrobials (greater than 50%) also may not be able topenetrate sequestered compartments, such as cerebral spinalfluid, resulting in insufficient concentration to inhibit bacteria.Second, some drugs may not achieve sufficient concentrations
antimicrobial concentrations are high. In contrast, concentration-independent (or time-dependent) activity refers to a minimalincrease in the rate or extent of bacterial killing with anincrease in antimicrobial dose. Concentration-independentantimicrobial activity is maximized when these antimicrobialsare dosed to maintain blood and/or tissue concentrationsabove the MIC in a time-dependent manner. Fluoroquinolones,aminoglycosides, and metronidazole are examples ofantimicrobials that exhibit concentration-dependent activity,whereas β-lactam and glycopeptide antimicrobials exhibitconcentration-independent activity. Pharmacodynamic propertieshave been optimized to develop new dosing strategiesfor older antimicrobials. Examples include single-daily-doseaminoglycoside or β-lactam therapy administered by continuousor extended infusion. The product labeling for manynew antimicrobials takes pharmacodynamic properties intoaccount.Antimicrobials also can be classified as possessing bactericidalor bacteriostatic activity in vitro. Bactericidal antibioticsgenerally kill at least 99.9% (3 log reduction) of a bacterialpopulation, whereas bacteriostatic antibiotics possess antimicrobialactivity but reduce bacterial load by less than 3 logs. Clinically,bactericidal antibiotics may be necessary to achievesuccess in infections such as endocarditis or meningitis.A full discussion of the application of antimicrobial pharmacodynamicsis beyond the scope of this chapter, but excellentsources of information are available.18
A major concern when selecting antimicrobial regimens shouldbe the propensity for the regimen to cause adverse effects andthe potential for interaction with other drugs. Patients maypossess characteristics or risk factors that increase their likelihoodof developing an adverse event, emphasizing the needto obtain a good patient medical history. In general, if severaldifferent antimicrobial options are available, antimicrobialswith a low propensity to cause specific adverse events shouldbe selected, particularly for patients with risk factors for aparticular complication. Risk factors for adverse events mayinclude the coadministration of other drugs that are associatedwith a similar type of adverse event. For example, coadministrationof the known nephrotoxin gentamicin withvancomycin increases the risk for nephrotoxicity compared with administration of either drug alone.19 Other drug interactionsmay predispose the patient to dose-related toxicitythrough inhibition of drug metabolism. For example, erythromycinhas the potential to prolong cardiac QT intervalsin a dose-dependent manner, potentially increasing the riskfor sudden cardiac death. A cohort study of patients takingoral erythromycin found that patients with concomitantlyprescribed medications that inhibited the metabolism oferythromycin exhibited a fivefold increase in cardiac deathversus controls.20
regulatory studies are not designed to identify differences inhospital length of stay, less common adverse events, monitoringcosts, collateral damage, or antimicrobial-specific resistanceissues, all of which may contribute to medical costs.Careful consideration of antimicrobial microbiologic, pharmacologic,and patient-related factors such as complianceand a variety of clinical outcomes is necessary to establishthe cost versus benefit of an antimicrobial in a given patient.If there is no difference or a small difference in these factors,the least costly antimicrobial may be the best choice.Patient Considerations inAntimicrobial Selection8 Key patient-specific considerations in antimicrobialselection include recent previous antimicrobial exposures,identification of the anatomic location of infection throughphysical examination and diagnostic imaging, history of drugallergies, pregnancy or breast-feeding status, organ dysfunctionthat may affect drug clearance, immunosuppression, compliance,and the severity of illness (see Table 69–2).
Host factors can help to ensure selection of the most appropriateantimicrobial agent. Age is an important factor in antimicrobialselection. With regard to dose and interval, renal andhepatic function varies with age. Populations with diminishedrenal function include neonates and the elderly. Hepatic functionin the neonate is not fully developed, and drugs thatare metabolized or eliminated by this route may produceadverse effects. For example, sulfonamides and ceftriaxonemay compete with bilirubin for binding sites and may resultin hyperbilirubinemia and kernicterus. Gastric acidity alsodepends on age; the elderly and children younger than 3 yearsof age tend to be achlorhydric. Drugs that need an acidic environment(e.g., ketoconazole) are not well absorbed, and thosewhose absorption is enhanced in an alkaline environment willhave increased concentrations (e.g., penicillin G).Disruption of host defenses due to IV or indwelling Foleycatheters, burns, trauma, surgery, and increased gastric pH (secondary to antacids, H2 blockers, and proton pump inhibitors)may place patients at higher risk for infection. Breaks in skinintegrity provide a route for infection because the naturalbarrier of the skin is disrupted. Increased gastric pH canallow for bacterial overgrowth and has been associated withan increased risk of pneumonia.21
Recognizing the presumed site of infection and mostcommon pathogens associated with the infectious sourceshould guide antimicrobial choice, dose, and route of administration.For example, community-acquired pneumoniais caused most commonly by S. pneumoniae, E. coli is theprimary cause of uncomplicated UTIs, and staphylococciand streptococci are implicated most frequently in skin andskin-structure infections (e.g., cellulitis).
Patients with a history of recent antimicrobial use mayhave altered normal flora or harbor resistant organisms. If apatient develops a new infection while on therapy, fails therapy,or has received antimicrobials recently, it is prudent toprescribe a different class of antimicrobial because resistanceto the current treatment is likely. Previous hospitalizationor healthcare utilization (e.g., residing in a nursing home,hemodialysis, and outpatient antimicrobial therapy) are riskfactors for the acquisition of nosocomial pathogens, whichare often resistant organisms.Antimicrobial allergies are some of the most commondrug-related allergies reported and have significant potentialto cause adverse events. In particular, penicillin-relatedallergy is common and can be problematic because there isan approximately 4% cross-reactivity with cephalosporinsas well as carbapenems.22,23 In general, a patient’s medicalhistory should be reviewed to determine the offendingβ-lactam and nature of the allergic reaction. In some cases,patients with mild or nonimmunologic reactions may receivea β-lactam antimicrobial with low cross-reactive potential.However, patients with a history of physical findings consistentwith IgE-mediated reactions such as anaphylaxis, urticaria,or bronchospasm should not be administered any typeof β-lactam antimicrobial, including cephalosporins, unlessthere are no other alternatives, and even then they shouldbe administered with caution. Administration of potentially cross-reactive agents in this situation should occur onlyunder controlled conditions, and some patients may needto undergo desensitization. If the specific medical historyrelating to a reported allergy cannot be obtained, the patientshould be assumed to have had an IgE-mediated reactionand should be managed in a similar manner. Monobactams(i.e., aztreonam) may be administered to patients with IgEmediatedallergic reactions to penicillin and are therefore anappropriate choice in these patients.
Renal and/or hepatic function should be considered inevery patient prior to initiation of antimicrobial therapy. Ingeneral, most antimicrobials undergo renal elimination andexhibit decreased clearance with diminished renal function,and dosing adjustments are frequently necessary and recommendationsfor adjustment are available in the literature.24 Incontrast, dosing adjustments for antimicrobials that undergononrenal elimination are less well documented. Failure toadjust the antimicrobial dose or interval may result in drugaccumulation and an increase in adverse effects.Concomitant administration of other medications mayinfluence the selection of the antimicrobial, dose, and monitoring.Medications that commonly interact with antibioticsinclude, but are not limited to, warfarin, rifampin, phenytoin,digoxin, theophylline, multivalent cations (e.g., calcium,magnesium, and zinc), and sucralfate. Drug interactionsbetween antimicrobials and other medications may occur viathe cytochrome P-450 system, protein-binding displacement,and alteration of vitamin K–producing bacteria. Interactionsmay result in increased concentrations of one or both agents,increasing the risk of adverse effects or additive toxicity.A key consideration in selecting antimicrobial regimens startswith obtaining a good patient medical and drug history,recognizing drug-specific adverse-event characteristics, andanticipating potential problems proactively. If it is necessaryto use an antimicrobial with a relatively high frequency ofadverse effects, informing patients of the risks and benefits oftherapy, as well as what to do if an adverse effect occurs, mayimprove patient compliance and may facilitate patient safety.Antimicrobial agents must be used with caution in pregnantand nursing women. Some agents pose potential threats to
the fetus or infant (e.g., quinolones, tetracyclines, and sulfonamides).For some agents, avoidance during a specific trimesterof pregnancy is warranted (e.g., the first trimester with trimethoprim/sulfamethoxazole). Pharmacokinetic variables alsoare altered during pregnancy. Both the clearance and volumeof distribution are increased during pregnancy. As a result,increased dosages and/or more frequent administration of certaindrugs may be required to achieve adequate concentrations.This information can be obtained from a number of sources.25,26
Adherence is essential to ensure efficacy of a particularagent. Patients may stop taking their antibiotics once thesymptoms subside and save them for a “future” infection.If the patient does not complete the course of therapy, theinfection may not be eradicated, and resistance may emerge.Self-medication of saved antibiotics may be harmful, leadingto overtreatment, which may further contribute to antibioticresistant. Poor patient adherence may be due to adverseeffects, tolerability, cost, and lack of patient education.
OUTCOME EVALUATIONFigure 69–4 provides an overview of patient- and antimicrobialagent–specific factors to consider when selectingan antimicrobial regimen. It further delineates monitoringof therapy and actions to take depending on the patient’sresponse to therapy. The duration of therapy depends onpatient response and type of infection being treated.Modifying Empirical Therapy Based onCultures and Clinical ResponseIf a successful clinical response occurs and culture resultsare available, therapy should be de-escalated. Antibioticde-escalation generally refers to the discontinuation of antibioticsthat are providing a spectrum of activity greater than
necessary to treat the infection, discontinuation of duplicativespectrum antibiotics, or switching to a narrower spectrumantibiotic once a patient is clinically stable. De-escalation ofempirical therapy may also include discontinuing antibioticsbased on clinical criteria and negative culture results, suchas the absence of antibiotic-resistant pathogens.27 The purposeof de-escalation therapy is to minimize the likelihoodof secondary infections owing to antimicrobial-resistantorganisms. In cases in which a specific organism is recoveredthat has a known preferred agent of choice, therapy might bechanged to that specific agent. For example, antistaphylococcalpenicillins are considered to be the agents of choice formethicillin-susceptible S. aureus owing to their bactericidalactivity and narrow-spectrum activity and may be preferableto other antibiotic regimens. In other cases, empirical coveragemight be discontinued if a specific suspected pathogen isexcluded by culture or an alternative, noninfectious diagnosisis established. In addition, IV antimicrobials frequentlyare more expensive than oral therapy. Therefore, it is usuallydesirable to convert therapy to oral antimicrobials with acomparable antimicrobial spectrum or specific pathogensensitivity as soon as the patient improves clinically.28
Failure of Antimicrobial TherapyWhile many infections respond readily to antimicrobials,some infections do not. A relatively common question whena patient’s condition fails to improve relates to whether theantimicrobial therapy has failed. Changing antimicrobialsgenerally is one of the easiest interventions relative to otheroptions. However, it is important to remember that antimicrobialtherapy comprises only a portion of the overall disease
treatment, and there may be many factors that contribute toa lack of improvement. 0 In general, inadequate diagnosisresulting in poor initial antimicrobial or other nonantibioticdrug selection, poor source control, or the development of a newinfection with a resistant organism are relatively common causesof antimicrobial failure. An infection-related diagnosis maybe difficult to establish and generally has two components:(a) differentiating infection from noninfection-related diseaseand (b) providing adequate empirical spectrum of activity if of secondary infections. In this case, the patient generallyimproves, but then develops a new infection caused by anantimicrobial-resistant pathogen and relapses. The emergenceof resistance to a targeted pathogen while on antimicrobialtherapy can be associated with clinical failure but usuallyis limited to tuberculosis, pseudomonads, or other gramnegativeenterics. Drug- and patient-specific factors such asappropriate dosing, patient compliance, and drug interactionscan be associated with therapeutic failure and also should be the cause is infectious. Failure of improvement in a patient’scondition should warrant broadening the differential diagnosisto include noninfection-related causes, as well as consideringother potential infectious sources and/or pathogenic organisms.Another common cause of failure is poor source control.A diagnostic search for unknown sources of infection andremoval of indwelling devices in the infected environment orsurgical drainage of abscesses should be undertaken if thepatient’s condition is not improving. Less common but still
frequent causes of therapeutic failure include the development considered. A common assumption is that the correct diagnosiswas made, but the patient was not treated long enoughwith antimicrobials. There are certain types of infections (e.g.,endocarditis or osteomyelitis) where the standard of care isto treat for prolonged periods of time (i.e., weeks or months).However, the optimal duration of therapy for many infectiousdiseases is somewhat subjective. Recently, studies of severalinfectious processes have suggested that shorter durationsof therapy can result in similar clinical outcomes as longerdurations of therapy, frequently with fewer complications orsecondary infections.29–31 The general trend has been to treatthese disease processes with shortened courses of antibiotictherapy. In this period of extensive antimicrobial resistance,clinicians should keep abreast of changing recommendationsemphasizing shorter durations of therapy.
CONCLUSIONAntimicrobial regimen selection is a complex process involvingthe integration of a multitude of factors. The guiding principlesto make the diagnosis and do no harm must be consideredwhen choosing an antimicrobial for a given patient.In summary, when infection is suspected, rapid and accuratediagnosis should be followed by early intervention thatincludes administration of appropriately dosed antibioticswith appropriate empirical spectra. De-escalation to suitablenarrow-spectrum antibiotics if susceptibilities are knownshould occur as soon as possible, and therapy should bestopped as soon as the patient is cured. These fundamentalactions improve infectious disease outcomes and minimize
collateral damage and adverse effects.
Regimen antimikroba
Pilihan
Setelah menyelesaikan bab ini, pembaca akan dapat:
1. Mengakui bahwa resistensi antimikroba adalah konsekuensi tak terelakkan dari terapi antimikroba.
2. Jelaskan bagaimana antimikroba berbeda dari kelas obat lain dalam hal efek mereka pada individu
pasien serta pada masyarakat secara keseluruhan.
3. Mengidentifikasi dua prinsip panduan untuk dipertimbangkan ketika merawat pasien dengan antimikroba, dan menerapkan
prinsip-prinsip ini dalam perawatan pasien.
4. Bedakan antara kolonisasi mikroba dan infeksi berdasarkan riwayat pasien, fisik
pemeriksaan, dan laboratorium dan budaya hasil.
5. Mengevaluasi dan menerapkan setidaknya enam pertimbangan obat-spesifik utama ketika memilih antimikroba
terapi.
6. Mengevaluasi dan menerapkan setidaknya tujuh pertimbangan-pasien tertentu utama ketika memilih
terapi antimikroba.
7. Pilih terapi antimikroba empiris berdasarkan spektrum-of-aktivitas pertimbangan yang menyediakan
respon sebanding dengan tingkat keparahan penyakit diukur. Memberikan alasan untuk mengapa diukur
respon dalam pemilihan antimikroba yang sesuai.
8. Mengidentifikasi dan menerapkan lima prinsip utama pendidikan pasien dan respon pemantauan untuk
terapi antimikroba.
9. Mengidentifikasi dua penyebab umum dari pasien gagal untuk memperbaiki sementara di antimikroba
Penemuan antimikroba adalah salah satu yang terbesar
prestasi medis dari abad ke-20. Sebelum
era antimikroba, pasien yang terjangkit umum
penyakit menular morbiditas yang signifikan dikembangkan atau
binasa. Penemuan penisilin pada tahun 1927, diikuti oleh
Penemuan selanjutnya antimikroba lainnya, memberikan kontribusi untuk
penurunan yang signifikan dalam angka kematian terkait penyakit menular
selama lima dekade berikutnya. Namun, sejak tahun 1980, menular
kematian terkait penyakit di Amerika Serikat telah meningkat,
sebagian karena peningkatan resistensi antimikroba.
Penemuan hampir setiap kelas baru antimikroba
telah terjadi dalam menanggapi perkembangan bakteri
perlawanan dan kehilangan efektivitas klinis yang ada
antimikroba. 1 Sebuah konsekuensi tak terelakkan dari mengekspos
mikroba terhadap antimikroba adalah bahwa beberapa organisme akan mengembangkan
resistensi terhadap antimikroba tersebut. Hari ini, ada puluhan
kelas antimikroba dan ratusan antimikroba yang tersedia
untuk penggunaan klinis. Namun, dalam banyak kasus, perbedaan
Mekanisme aksi antara antimikroba yang kecil,
dan sifat mikrobiologis dari agen yang sama.
2 Antimikroba berbeda dari kelas-kelas lain dari obat-obatan
karena mereka mengerahkan aksi mereka pada bakteri menginfeksi
tuan rumah sebagai lawan bertindak langsung pada host. Karena penggunaan
dari antimikroba pada satu pasien mempengaruhi tidak hanya pasien yang
tetapi juga pasien lain jika mereka terinfeksi tahan
bakteri, pilihan yang benar, penggunaan, dan pemantauan klinis
respon adalah hal yang terpenting.
3 Ada dua prinsip yang perlu dipertimbangkan ketika
merawat pasien dengan antimikroba: (a) membuat yang benar
diagnosis dan (b) tidak membahayakan! Pasien dengan infeksi
sering hadir dengan tanda-tanda dan gejala yang
spesifik untuk infeksi dan mungkin bingung dengan lainnya
penyakit tidak menular. Tidak hanya itu penting untuk menentukan
apakah proses penyakit adalah asal menular, tapi
juga penting untuk menentukan penyebab yang spesifik
patogen dari infeksi. Antimikroba bervariasi dalam mereka
spektrum aktivitas, kemampuan untuk menghambat atau membunuh berbeda
spesies bakteri. Antimikroba yang membunuh banyak berbeda
spesies bakteri yang disebut antimikroba spektrum luas,
sedangkan antimikroba yang membunuh hanya beberapa spesies
bakteri disebut antimikroba spektrum sempit. Satu
mungkin berpendapat bahwa semua orang memperlakukan dengan antimikroba yang luas
antimikroba akan meningkatkan kemungkinan bahwa
pasien akan mendapatkan yang lebih baik bahkan tanpa mengetahui bakteri
menyebabkan infeksi. Namun, bertentangan dengan argumen ini
prinsip "Apakah tidak membahayakan!" cakupan luas antimikroba
tidak meningkatkan kemungkinan pembunuhan secara empiris
patogen penyebab; sayangnya, perkembangan
infeksi sekunder dapat disebabkan oleh pemilihan antimicrobial-
patogen nontargeted tahan. Tambahan lagi,
efek samping diperkirakan mempersulit hingga 10% dari semua
terapi antimikroba, dan untuk agen pilih, adverseevent yang
Tarif mirip dengan obat berisiko tinggi seperti
warfarin, digoksin, atau insulin.1 Oleh karena itu, tujuan keseluruhan
terapi antimikroba harus untuk menyembuhkan pasien
infeksi; membatasi bahaya dengan meminimalkan risiko pasien untuk
efek samping, termasuk infeksi sekunder; dan batas
risiko sosial dari bakteri antimikroba tahan.
EPIDEMIOLOGI DAN ETIOLOGI
Penyakit-penyakit yang berhubungan dengan infeksi, terutama pernafasan
Infeksi saluran, adalah salah satu yang paling umum alasan pasien
mencari care.2 medis antimikroba resep di masa lalu
telah dikaitkan dengan penggunaan yang tidak antimikroba
agen. Selama akhir 1990 / awal 2000-an, banyak organisasi
kampanye dimulai untuk mempromosikan antimikroba yang tepat
menggunakan. Tren terbaru dalam resep menyarankan pengurangan sederhana
digunakan antimikroba untuk infeksi ini, menunjukkan
pengakuan meningkat dari konsekuensi negatif dari
antimikroba use.4 Peresepan antimikroba di rumah sakit
pasien juga umum, sebagai sampai satu-setengah dari semua pasien
menerima setidaknya satu antimikroba selama rawat inap.
Pada tahun 2002, perkiraan jumlah infeksi nosokomial adalah
1,8 juta, dengan perkiraan 99.000 deaths.5 Pada tahun 2009, CDC
melaporkan aliran darah line-terkait tengah 25.000 lebih sedikit
Infeksi dari tahun 2001, sebuah reduction.6 58% infeksi nosokomial
cenderung dikaitkan dengan strain yang resisten antimikroba
bakteri. Namun, telah terjadi pergeseran dalam etiologi
beberapa infeksi masyarakat yang didapat. Semakin, infeksi
disebabkan oleh patogen yang resisten antimikroba, tradisional
nosokomial di asal, sedang diidentifikasi dalam perawatan rawat jalan
pengaturan. Alasan untuk perubahan ini mencakup penduduk penuaan,
perbaikan dalam pengelolaan kondisi komorbiditas kronis
termasuk kondisi imunosupresif, dan meningkat
dalam pengelolaan rawat jalan pasien lebih lemah. The
Sebagian besar infeksi yang disebabkan oleh patogen antimikroba-tahan
dalam pengaturan rawat jalan terjadi pada pasien yang memiliki
memiliki eksposur baru untuk beberapa aspek dari sistem kesehatan
Oleh karena itu dan didefinisikan sebagai infeksi-kesehatan terkait.
The konvergen etiologi bakteri dan meningkatkan resistensi
di semua lingkungan kesehatan menekankan perlunya untuk "membuat
diagnosis. "
PATOFISIOLOGI
Flora normal dan Infeksi endogen
Banyak area tubuh manusia dijajah dengan bacteria-
ini dikenal sebagai flora normal. Infeksi sering muncul dari
sendiri Flora seseorang normal (juga disebut infeksi endogen).
Infeksi endogen dapat terjadi ketika ada perubahan
dalam flora normal (misalnya, penggunaan antimikroba baru-baru ini mungkin
memungkinkan untuk pertumbuhan berlebih dari flora normal lainnya) atau gangguan
pertahanan host (misalnya, istirahat atau entri di kulit). Mengetahui
apa organisme berada dengan di mana dapat membantu untuk memandu antimikroba empiris
Terapi (Gbr. 69-1). Selain itu, itu bermanfaat
tahu apa situs anatomi biasanya steril. Ini
termasuk cairan serebrospinal, darah, dan urin.
Menentukan Kolonisasi Versus Infeksi
Infeksi mengacu pada keberadaan bakteri yang menyebabkan
penyakit (misalnya, organisme yang ditemukan dalam biasanya steril
situs anatomi atau di situs steril dengan tanda-tanda / gejala
infeksi). Kolonisasi mengacu pada keberadaan bakteri yang
tidak menyebabkan penyakit. 4 Hanya bakteri yang menyebabkan penyakit
harus ditargetkan dengan terapi antimikroba, dan non-
Penyakit-memproduksi menjajah tumbuhan harus dibiarkan utuh. Saya t
penting untuk membedakan infeksi dari penjajahan
karena terapi antimikroba menargetkan kolonisasi bakteri
adalah tidak pantas dan dapat menyebabkan perkembangan
bakteri resisten.
Eksogen Acquired Infeksi Bakteri
Infeksi yang diperoleh dari sumber eksternal yang disebut sebagai
infeksi eksogen. Infeksi ini dapat terjadi sebagai akibat
dari manusia ke manusia transmisi, kontak dengan eksogen
populasi bakteri di lingkungan, dan kontak hewan.
Patogen tahan seperti methicillin-resistant Staphylococcus
aureus (MRSA) dan vancomycin-resistant Enterococcus
spp. (VRE) mungkin menjajah pasien rawat inap atau pasien
yang mengakses sistem kesehatan sering. Ini adalah kunci untuk
tahu mana pasien telah memperoleh organisme ini karena
pasien umumnya menjadi dijajah sebelum mengembangkan
pasien infeksi, dan terjajah harus ditempatkan dalam isolasi
(per kebijakan pengendalian infeksi) untuk meminimalkan transmisi untuk
pasien lain.
Kontras bakteri Virulensi
dan Resistance
Virulensi mengacu pada patogenisitas atau penyakit keparahan diproduksi
oleh organisme. Banyak bakteri dapat menghasilkan toksin atau
memiliki karakteristik pertumbuhan yang berkontribusi terhadap patogenisitas mereka.
Beberapa faktor virulensi memungkinkan organisme untuk menghindari
respon imun dari host dan menyebabkan penyakit yang signifikan.
Virulensi dan resistensi adalah karakteristik mikroba yang berbeda.
Misalnya, Streptococcus pyogenes, penyebab umum
infeksi kulit, menghasilkan racun yang dapat menyebabkan penyakit parah,
namun sangat rentan terhadap penisilin. Enterococcus faecium adalah organisme yang sangat tahan tapi sering flora menjajah
yang menyebabkan penyakit terutama di immunocompromised.
PRESENTASI KLINIS
DAN DIAGNOSIS
Pemeriksaan fisik
Temuan pada pemeriksaan fisik, bersama dengan klinis
presentasi, dapat membantu untuk menyediakan lokasi anatomi dari
infeksi. Setelah situs anatomi diidentifikasi, yang paling mungkin
patogen yang berhubungan dengan penyakit dapat ditentukan
berdasarkan kemungkinan endogen atau eksogen tumbuhan.
Demam sering menyertai infeksi dan didefinisikan sebagai kenaikan
suhu tubuh di atas normal 37C (98.6F). Lisan
dan suhu aksila mungkin meremehkan suhu inti
oleh setidaknya 0.6C (1F), sedangkan suhu rektal terbaik
suhu inti perkiraan. Demam merupakan respon host untuk
racun bakteri. Namun, infeksi bakteri yang tidak
satunya penyebab demam. Demam juga bisa disebabkan oleh infeksi lain
(misalnya, jamur atau virus), obat-obatan (misalnya, penisilin,
sefalosporin, salisilat, dan fenitoin), trauma, atau lainnya
kondisi medis (misalnya, penyakit autoimun, keganasan,
emboli paru, dan hipertiroidisme). Beberapa pasien
dengan infeksi dapat hadir dengan hipotermia (misalnya, pasien
dengan infeksi yang luar biasa). Pasien tua mungkin demam,
sebagai mungkin orang-orang dengan infeksi lokal (misalnya kemih
infeksi saluran) 0,7 Bagi yang lain, demam mungkin satu-satunya indikasi
infeksi. Sebagai contoh, pasien neutropenia mungkin tidak memiliki
kemampuan untuk me-mount respon imun normal terhadap infeksi
(misalnya, menyusup di dada x-ray, piuria pada urinalisis, atau
eritema atau indurasi sekitar lokasi kateter), dan satu-satunya
Temuan mungkin demam.
Studi pencitraan
Pencitraan juga dapat membantu untuk mengidentifikasi lokalisasi anatomis
infeksi. Studi-studi ini biasanya dilakukan
dalam hubungannya dengan tes lain untuk membangun atau aturan
keluar adanya infeksi. Radiografi dilakukan
umumnya untuk menegakkan diagnosis pneumonia,
serta untuk menentukan beratnya penyakit (single vs
multilobe keterlibatan). Computed tomography (CT)
scan adalah jenis x-ray yang menghasilkan tiga dimensi
gambar dari kombinasi jaringan lunak, tulang, dan darah
kapal. Sebaliknya, magnetic resonance imaging (MRI)
menggunakan gelombang radio elektromagnetik untuk menghasilkan dua atau tiga dimensi
gambar dari jaringan lunak dan pembuluh darah dengan
kurang detail dari struktur tulang. Nonmicrobiologic Studi Laboratorium
Tes laboratorium nonmicrobiological umum termasuk
jumlah sel darah putih (WBC) dan diferensial, eritrosit
Tingkat sedimentasi (ESR), dan penentuan biomarker
C-reactive protein (CRP) atau prokalsitonin tingkat. Di sebagian besar
kasus, jumlah WBC meningkat pada respon terhadap infeksi,
tapi mungkin akan menurun karena berlebihan atau lama
infeksi. Adalah persentase masing-masing diferensial The
jenis WBC (Tabel 69-1). Dalam respon terhadap stres fisiologis,
neutrofil meninggalkan aliran darah dan memasuki jaringan untuk
"Berperang" melawan patogen menyinggung (yaitu, leukositosis).
Hal ini penting untuk mengenali leukositosis yang spesifik
untuk infeksi dan mungkin sementara terjadi dalam menanggapi menular
kondisi seperti infark miokard akut.
Selama infeksi, neutrofil imatur (misalnya, band) yang
dirilis pada tingkat meningkat untuk membantu melawan infeksi, yang menyebabkan
apa yang dikenal sebagai bandemia atau pergeseran kiri. Oleh karena itu, WBC
count diferensial adalah kunci untuk menentukan apakah infeksi
hadir. Beberapa pasien mungkin hadir dengan total yang normal
WBC dengan pergeseran kiri (misalnya, orang tua). ESR dan CRP adalah penanda nonspesifik peradangan yang meningkatkan sebagai hasilnya
dari fase akut respon reaktan, yang merupakan tanggapan
rangsangan inflamasi seperti infeksi atau cedera jaringan.
Tes-tes ini dapat digunakan sebagai penanda penyakit menular
Tanggapan karena mereka meningkat ketika penyakit ini
akut aktif dan biasanya jatuh dalam menanggapi pengobatan yang berhasil.
Dokter mungkin menggunakan tes ini untuk memantau pasien
respon terhadap terapi di osteomyelitis dan endokarditis infektif.
Tes ini tidak boleh digunakan untuk mendiagnosa infeksi
karena mereka mungkin meningkat di inflamasi menular
kondisi (misalnya, rheumatoid arthritis, polymyalgia rheumatica,
dan arteritis temporalis). Sebaliknya, prokalsitonin, sebuah
prohormon kalsitonin, cepat diproduksi dalam menanggapi
infeksi bakteri. Kadar serum prokalsitonin dalam hubungannya
dengan temuan klinis semakin sering digunakan untuk menilai
baik kebutuhan untuk memulai terapi antibiotik serta menentukan
ketika terapi antibiotik dapat dengan aman dihentikan. Nonmicrobiologic Studi Laboratorium
Tes laboratorium nonmicrobiological umum termasuk
jumlah sel darah putih (WBC) dan diferensial, eritrosit
Tingkat sedimentasi (ESR), dan penentuan biomarker
C-reactive protein (CRP) atau prokalsitonin tingkat. Di sebagian besar
kasus, jumlah WBC meningkat pada respon terhadap infeksi,
tapi mungkin akan menurun karena berlebihan atau lama
infeksi. Adalah persentase masing-masing diferensial The
jenis WBC (Tabel 69-1). Dalam respon terhadap stres fisiologis,
neutrofil meninggalkan aliran darah dan memasuki jaringan untuk
"Berperang" melawan patogen menyinggung (yaitu, leukositosis).
Hal ini penting untuk mengenali leukositosis yang spesifik
untuk infeksi dan mungkin sementara terjadi dalam menanggapi menular
kondisi seperti infark miokard akut.
Selama infeksi, neutrofil imatur (misalnya, band) yang
dirilis pada tingkat meningkat untuk membantu melawan infeksi, yang menyebabkan
apa yang dikenal sebagai bandemia atau pergeseran kiri. Oleh karena itu, WBC
count diferensial adalah kunci untuk menentukan apakah infeksi
hadir. Beberapa pasien mungkin hadir dengan total yang normal
WBC dengan pergeseran kiri (misalnya, orang tua). ESR dan CRP adalah penanda nonspesifik peradangan yang meningkatkan sebagai hasilnya
dari fase akut respon reaktan, yang merupakan tanggapan
rangsangan inflamasi seperti infeksi atau cedera jaringan.
Tes-tes ini dapat digunakan sebagai penanda penyakit menular
Tanggapan karena mereka meningkat ketika penyakit ini
akut aktif dan biasanya jatuh dalam menanggapi pengobatan yang berhasil.
Dokter mungkin menggunakan tes ini untuk memantau pasien
respon terhadap terapi di osteomyelitis dan endokarditis infektif.
Tes ini tidak boleh digunakan untuk mendiagnosa infeksi
karena mereka mungkin meningkat di inflamasi menular
kondisi (misalnya, rheumatoid arthritis, polymyalgia rheumatica,
dan arteritis temporalis). Sebaliknya, prokalsitonin, sebuah
prohormon kalsitonin, cepat diproduksi dalam menanggapi
infeksi bakteri. Kadar serum prokalsitonin dalam hubungannya
dengan temuan klinis semakin sering digunakan untuk menilai
baik kebutuhan untuk memulai terapi antibiotik serta menentukan
ketika terapi antibiotik dapat dengan aman dihentikan.
Sebuah diskusi penuh peran prokalsitonin dalam mendiagnosis
dan mengobati penyakit adalah di luar lingkup chapter.8,9 ini
Studi mikrobiologis
Studi mikrobiologi yang memungkinkan untuk pemeriksaan langsung dari
spesimen (misalnya, dahak, darah, atau air kencing) juga dapat membantu dalam
diagnosis dugaan dan memberikan indikasi karakteristik
organisme menginfeksi. Umumnya, budaya mikroba
diperoleh dengan noda Gram dari bahan berbudaya.
Noda Gram dari spesimen yang dikumpulkan dapat memberikan informasi yang cepat
yang dapat diterapkan segera untuk perawatan pasien. SEBUAH
Gram stain dilakukan untuk mengidentifikasi apakah bakteri
hadir dan untuk menentukan karakteristik morfologi dari
bakteri (misalnya, gram-positif atau gram negatif atau bentuk-
cocci, basil). Spesimen tertentu tidak noda baik atau sama sekali
dan harus diidentifikasi dengan teknik pewarnaan alternatif
