Principles of Antimicrobial Therapy (2025) PDF

PRINCIPLE S OF ANTIMICROB IAL THERAPY OBJECTIVES Which antibiotics may cause fever? Which bacteria are located where on your body? Classify gram(+), gram(-), anaerobic and atypical bacteria by morphology, oxygen demand, and enzyme activity What are the mechanisms of bacterial re...

PRINCIPLE S OF ANTIMICROB IAL THERAPY OBJECTIVES Which antibiotics may cause fever? Which bacteria are located where on your body? Classify gram(+), gram(-), anaerobic and atypical bacteria by morphology, oxygen demand, and enzyme activity What are the mechanisms of bacterial resistance (eg, VRSA)? https://youtu.be/ReKG-vuYHY4?si=iTGOHbHl7RpOAf8Y Know MOA (slide #49) Know the side / adverse effects of antibiotics Know comments section and spectrum of activity for antibiotics Know if an antibiotic is PO, IM or IV What are the upper limit CrCl cutoffs for PO antibiotics? IV dosing is NOT on the exam Pediatric Pearls are important to review SELECTING ANTIMICROBIALS  CONFIRM THE PRESENCE  SELECTION OF OF INFECTION PRESUMPTIVE  History and physical THERAPY exam  Host factors  Signs/Symptoms  Drug factors  Predisposing factors  MONITOR  IDENTIFICATION OF THERAPEUTIC PATHOGEN RESPONSE  Collection of infected  Clinical assessment material  Labs/diagnostic tests  Gram stain  Assessment of  Serology therapeutic failure  Culture & Sensitivity CONFIRMI NG THE PRESENCE OF INFECTIO N FEVER Hallmark sign of infectious diseases Normal temperature = 98°F–98.6°F Pyrogens act on body’s thermostat in hypothalamus, raising body temperature Drug-induced fever – persistent fever in the absence of infection or underlying condition – 5% off all drug reactions – β-lactams, anticonvulsants, allopurinol, hydralazine, nitrofurantoin, sulfonamides, phenothiazines, and methyldopa Non-infectious etiologies – false positive – Malignant hyperthermia – exposure to volatile inhalational anesthetic agents and succinylcholine (a muscle relaxant) False negative – no fever, but infection present – Patient intervening – medications on board that can mask fever Antipyretics (ASA, APAP, NSAIDs) Corticosteroids WBCs Most infections result in leukocytosis Nonspecific, other potential causes – Stress – Pregnancy – Inflammation – Medications – Leukemia WNLs = 4,000 – 10,000 cells/mm3 INFECTION = elevated usually up to 30,000 – 40,000 TYPES OF WBC DIFFERENTIAL GRANULOCYTES AGRANULOCYTES NEUTROPHILS MONOCYTES Up to 70% of WBC Mature = “segs” Immature = “bands” Elevated w/bacterial and fungal infections – “left shift” BASOPHILS LYMPHOCYTES Allergic reaction 15 – 40% of WBC T cells: cell mediated immunity B cells humoral immunity Elevated w/viral illness or unusual bacterial infections EOSINOPHILS Allergic reaction Parasitic infection LOCAL SIGNS Pain and inflammation – Inflammatory markers Erythrocyte sedimentation rate (ESR) – Settles faster = inflammation C-reactive protein (CRP) – Produced by liver in response to inflammation Interleukin (IL) Tumor necrosis factor alpha (TNF-alpha) Symptoms referable to an organ system – Help establish presence of infection – Aid in narrowing list of potential pathogens Figure 21.3 Events of acute inflammation. Innate defenses Internal defenses Initial stimulus Physiological response Signs of inflammation Tissue injury Result Release of inflammatory chemicals Release of leukocytosis- (histamine, complement, inducing factors kinins, prostaglandins, etc.) Leukocytosis (increased numbers of white blood cells in bloodstream) Arterioles Increased capillary Attract neutrophils, dilate permeability monocytes, and Cardinal Leukocytes migrate to lymphocytes to injured area area (chemotaxis) Signs of Local hyperemia (increased blood Capillaries leak fluid Margination Inflammation flow to area) (exudate formation) (leukocytes cling to capillary walls) Redness Leaked protein-rich Leaked clotting Diapedesis Heat (leukocytes pass through fluid in tissue spaces proteins form capillary walls) interstitial clots Swelling Heat Redness Pain Swelling that wall off area to prevent injury to Phagocytosis of pathogens surrounding tissue and dead tissue cells Pain (by neutrophils, short-term; by macrophages, long-term) Locally increased Possible temporary Temporary fibrin Pus may form temperature increases impairment of patch forms metabolic rate of cells function scaffolding Area cleared of debris for repair Healing © 2016 Pearson Education, Inc. Table 21.7 Selected Cytokines © 2016 Pearson Education, Inc.  UPPER RESPIRATORY MENINGITIS Streptococcus pyogenes Streptococcus pneumoniae Streptococcus pneumoniae Neisseria Haemophilus influenzae Haemophilus influenzae Moraxella catarrhalis GBS/E coli Listeria ENDOCARDITIS Staphylococcus LOWER RESPIRATORY Streptococcus viridans Community Enterococcus Streptococcus pneumoniae HACEK Haemophilus influenzae Atypicals: Legionella, INTRA-ABDOMINAL Mycoplasma Enteric GN Enteric GN, Hospital Enterococcus Staphylococcus, Pseudomonas Streptococcus Enteric GN Bacteroides spp. Streptococcus pneumoniae BONE AND JOINT URINARY TRACT Staphylococcus aureus E. coli, Proteus, Klebsiella Staphylococcus epidermidis Staphylococcus saprophyticus Streptococci Enterococcus Enterococcus Neisseria SELECTIO N OF EMPIRIC THERAPY RESOURCE S Infectious Diseases Society of American (IDSA) Guidelines The Sanford Guide – Pocket guide – Web edition  CONSIDERATIONS ORGANISMS KNOWN TO CAUSE THE INFECTION + GUIDELINES + ANTIBIOGRAM + FORMULARY + HOST CONSIDERATIONS – allergies, comorbidities, = organ function, previous antibiotics, previous cultures EMPIRIC THERAPY ANTIMICROBIAL STEWARDSHIP Improve patient safety & outcomes Antimicrobial Curb resistance stewardship Reduce adverse effects Cost effectiveness Consists of: ID physicians, pharmacists, micro lab, infection control Pharmacokinetic monitoring Examples of Using rapid diagnostic modalities interventions Preauthorization Timely transition from IV to PO therapy SANFORD ACTIVITY SPECTRA ANTIBIOGRAM Combines C&S from individual patients at one institution Help aid in making empiric antimicrobial decisions Used to monitor resistance patterns CULTURE & SUSCEPTIBILITY Bacteria are cultured and grown on agar plate Lab identifies minimum inhibitory concentration (MIC) and compares to susceptibility breakpoint (set by Clinical & Laboratory Standards Institute (CLSI)  Sensitive (S)  Intermediate (I)  Resistant (R)  Synergy (SYN) WHERE DO BREAKPOINTS COME FROM? IDENTIFIC ATION OF THE PATHOGEN TYPES OF CULTURES BLOOD – 2+ sets depending on indication, should not be collected through indwelling line/catheter, no sooner than 15 min apart URINE – midstream catch after appropriately disinfecting area SPUTUM – high polymorphonuclear (PMNs) and absence of squamous epithelial cells indicate good sample FLUID – Ascitic – Synovial fluid – Abscess – Peritoneal dialysate CSF TISSUE  GENERAL BACTERIA CATEGORIES GRAM STAINING MORPHOLOGY - Gram - Cocci negative - Bacilli/Rods - Gram positive - Spiral - Atypical OXYGEN DEMAND GROWTH PATTERN - Aerobic - Cluster - Anaerobic - Chain - Facultative - Diplococci anaerobe GRAM STAIN  STEP ONE GRAM POSITIVE: thick cell wall – stain dark purple/bluish GRAM NEGATIVE: thin cell wall – stain pink or reddish Atypical organisms – do NOT stain well – consider acid- fast stain CLASSIFICATION OF BACTERIA Gram Positive Organisms Gram Positive Organisms  GPC in clusters: Staphylococci ◦ S. aureus  Catalase and coagulase positive  Normal flora of nasal passages, skin, and mucous membranes  Skin and soft tissue infections, bacteremia, pneumonia, endocarditis, osteomyelitis, and TSS  Methicillin-resistant staphylococcus aureus (MRSA):  PBP2’ producing strains  Resistant to almost all beta-lactams  Nosocomial and community-acquired strains  Vancomycin generally considered drug of choice  Vancomycin-resistant staphylococcus aureus (VRSA)  Alter the structure of peptide side chain of peptidoglycan subunit Gram Positive Organisms  GPC in clusters: Staphylococci ◦ S. epidermidis  Coagulase-negative  Less virulent than S. aureus  Do not produce exotoxins  *** Part of normal flora on skin and mucous membranes  Frequent contaminant of blood cultures  Infections involving foreign objects  Catheters, prosthetic joints, prosthetic valves, dialysis shunts, shunt infections  Most strains are methicillin resistant (MRSE) Gram Positive Organisms  GPC in pairs or chains: Streptococci ◦ Pneumococci (S. pneumoniae)  Diplococcus  α-hemolytic, encapsulated  Commonly cause *pneumonia, otitis media, sinusitis, and *meningitis  Increasing levels of resistance to penicillin  Resistance status necessary for treatment of meningitis and otitis media  High rates of macrolide resistance Gram Positive Organisms  GPC in pairs or chains: Streptococci ◦ Viridans group streptococci  Large group of heterogeneous strep defined by hemolysis pattern  α-hemolytic (incomplete hemolysis)  Green discoloration (viridis)  Species: S. mutans, S. mitis, S. oralis, etc  Human flora  Colonize oral cavity, upper respiratory tract, GI tract, and urogenital tracts  Low virulence  Infections: infective endocarditis, dental caries, and infections in neutropenic patients Gram Positive Organisms  GPC in pairs or chains: Streptococci ◦ Group A (S. pyogenes)  β-hemolytic  Many virulence factors  Frequent cause of pharyngitis, scarlet fever, skin and soft tissue infections, and streptococcal toxic shock syndrome  Immune-mediated post-infection sequelae (can come back after being treated, if antibiotics aren’t taken for full course)  Rheumatic fever  Acute glomerulonephritis Gram Positive Organisms  GPC in pairs or chains: Streptococci ◦ Group B (S. agalactiae)  β-hemolytic (complete hemolysis)  Colonize female genital tract  Up to 40% of patients  Asymptomatic bacteriuria in pregnancy  Can cause sepsis, pneumonia, or meningitis in neonates and infants  May also cause infections in non-pregnant adults Gram Positive Organisms  GPC in chains: Enterococci ◦ Formerly streptococcus ◦ γ-hemolysis (no hemolysis) ◦ Two main species  E.faecalis  More common  E. faecium  More resistance ◦ Normal flora of GI tract ◦ Can cause: UTIs, bacteremia, endocarditis, wound infections, and intra-abdominal infections ◦ Intrinsically resistant to many antibiotics  Almost all drugs are bacteriostatic ◦ Vancomycin resistant enterococci (VRE) Gram Negative Organisms Gram Negative Organisms  Gram negative bacilli ◦ Enterobacteriaceae  Can inhabit human GI tract: “enteric”  E. coli, Proteus, Klebsiella  Can cause infections in healthy and immunocompromised individuals  UTIs, gastroenteritis, hospital-acquired pneumonia, bacteremia, wound infections, etc  Extended-spectrum beta-lactamase (ESBL)  Degrade all beta-lactams except carbapenems and sometimes β- lactam/β-lactamase inhibitors  Klebsiella  Often causes infections in patients with alcoholism  Cabapenemase (KPC)  Confers resistance to all beta-lactams  Proteus: almost exclusively cause UTIs Gram Negative Organisms  Gram negative bacilli ◦ Enterobacteriaceae  Serratia, Citrobacter, Enterobacter, Morganella  Can cause: bacteremia, pneumonia, surgical-site infections, UTI  AmpC-type β-lactamase:  Resistance to PCN, ampicillin/amoxicillin, 1st generation cephalosporins  SPACE-M  Serratia  Proteus, Pseudomonas  Acinetobacter  Citrobacter  Enterobacter  Morganella Gram Negative Organisms  Gram negative bacilli continued ◦ Non-fermenters  Acinetobacter baumanii  Colonizes skin, wounds, respiratory and GI tracts  Can cause institutional outbreaks  May cause: respiratory tract infections, bacteremia, wound infections, and catheter associated UTIs  Increasing rates of resistance  Stenotrophomonas maltophilia  Nosocomial pathogen with intrinsic resistance Gram Negative Organisms  Gram negative bacilli continued ◦ Non-fermenters  Pseudomonas aeruginosa  Many virulence factors  Contribute to tissue damage  Help with motility and adherence  Polysaccharide membrane that surrounds and protects from the environment making antibiotic penetration difficult  Frequent cause of hospital-acquired infections  Increased risk with loss of anatomical/physiological barrier, recent antibiotic use, prolonged hospitalizations  Pneumonia, UTI, surgical-site infection, bacteremia, etc.  Harbors many resistance mechanisms  Can develop resistance during treatment  Combination therapy commonly used empirically Gram Negative Organisms  Gram negative coccobacilli ◦ Haemophilus influenzae  Upper respiratory tract  Strains  Typeable: encapsulated  Six serotypes: a-f  Type b: invasive infections  Meningitis, epiglotittis, pneumonia, bacteremia, septic arthritis  HIB vaccine: highly effective 