• inhibitors of cell wall synthesis
  • beta lactams
  • glycopeptides
• inhibitors of protein synthesis
  • macrolides
  • tetracycline
  • aminoglycosides
  • oxazolidinones (linezolid)
  • telithromycin
• inhibitors of nucleic acid syn. and function
  • fluoroquinolones
  • rifampin
• inhibitors of metabolism
  • SULFA-TRP

• tetracycline
• sulfonamides
• macrolides
• lincosamides

• penicillins
• cephalosporins
• aminoglycosides
• fluoroquinolones

• slower response time
• require good host immune response
• use for less serious infections at non critical site

• faster onset
• better efficacy in immunocompromised
• recommended for serious, life threatening infection

• prophylactic- prevent infection
  • ex: SMP/TMP for PCP
• emperic- broad coverage pending definitive microbiologic dx
• therapeutic- definitive therapy if site and organism are known

• post exposure (HIV, meningitis, anthrax)
• immunocompromised host
  • HIV
  • asplenia
  • neutropenia
• travelers- malaria px
• procedural (surgery)
  • usually short course
  • endocarditis px with dental procedures
  • pre op antibiotics to prevent surgical site infections

• suspect infection based on HPE, labs
• pick antibiotics based on:
  • likely organisms
  • local susceptibility trends
  • patient specific factors
• make every effort to obtain cultures before starting antibiotics
  • but dont delay starting antibiotics if patient seriously ill

• first, establish need for antibiotic therapy
• when NOT to tx emperically
  • viral or minor bacterial disease
  • common cold
  • viral diarrhea
  • sore throat
  • sinusitis
  • these are self limiting and can wait for results of investigation before starting antibiotics
• microbiology should guide therapy if possible
• indication should be evidence based
• narrowest spectrum required
  • if start empirically with broad spectrum, multiple antibiotics, rationalize once cultures and sensitivities known
• dosage appropriate to site and type of infection
• minimize duration of therapy

• ID infecting organism
• antimicrobial susceptibility of infecting organism
• site of infection
• host factor
  • HS to agent
  • pregnancy
  • age
  • immunosuppression
  • genetic/metabolic factors
  • metabolism/excretion of antimicrobials
• side effect profile
• drug-drug interactions
• convenience
  • dosing schedule, number of pills
  • route of admin (some drugs not orrally bioavailable)
• cost

• stains: gram stain, AFB, fungal
  • pus, sputum, CSF, pleural fluid, tissue
  • most informative if organism seen on normally sterile specimen (less likely to be contaminant or colonizer)
• other rapid tests- Ag detection, PCR
• serology- virus, ricketsial infection
• isolation of organism- culture
• remember in most cases, it is impossible to ID organism for starting antimicrobial
• use knowledge of most likely organism for particular clinical syndrome to choose antimicrobial pending confirmation of etiologic agent
  • ex: cellulitis is S aureus or GAS

• disc diffusion
• E test (gradient of antimicrobial impregnated into plastic strip)
• MIC (serial dilutions of antimicrobial in agar or broth)
  • minimum dilution at which growth visibly inhibited

Remeber, this is more difficult to do for viruses, fungi, and parasites, so not routinely done.

• use known patterns of particular organisms
  • intrinsic factors
    • Pseudomonas R to cephalosporins except 3rd generation (ceftazidime)
    • Klebsiella intrinsically R to ampicillin
    • most anaerobes except Bacteroides are susceptible to penicillin
    • all anaerobes R to aminoglycosides because oxygen required for entry into bacterial cells
• if unknown susceptibilities, use geographic growth factors
  • local suceptibility patterns

• must deliever to site of infection at effective concentrations
• usually concentration should be greater than MIC
  • subinhibitor concentrations may damage organism and allow host immune system to act

• 3rd generation cephalosporins attain high levels in CSF
• penicillin G, ampicillin can reach adequate levels of CSF if administered in high doses

important in choosing antibiotic for CNS infections

• endocarditis, osteomyelitis, devitalized tissue
  • need high dose, prolonged therapy to achieve adequate concentrations at site of infection
• prostatitis
  • fluoroquinolones penetrate much better than beta lactams or aminoglycosides

• fully crossreactive to other penicillins and imipenem
• may cross react with cephalosporins (more so in first generation)
• not cross reactive with aztreonam

• other sulfonamides (includes diuretics)
• esp. common in HIV patients

• rash (all)
• diarrhea (all)
• nephrotoxicity (caution: preexisting renal insufficiency)
  • amphotericin B
  • aminoglycosides
• photosensitivity: tetracycline

• avoid
  • tetracyclines (discoloration of fetal teeth)
  • tigecycline (teratogenic)
  • aminoglycosides (hearing problems)
  • fluoroquinones (articular defects)
• relatively safe
  • penicillin
  • cephalosporin
  • erythromycin and azithromycin
  • daptomycin
  • clindamycin
  • amphotericin B

• infants have lower gastric acidity
  • increase penicillin absorption
  • decrease ketoconazole absorption
• renal function reduced in neonates and elderly (drugs excreted in kidney have longer half life)
• hepatic function underdeveloped in neonates
• tetracyclines bind to bone and teeth (discoloration and hypoplasia)
• fluroquinolones: carilage development and arthropathy in developing animals
  • CI: prepubertal children

• HIV, post transplant, chemotx
• increase chance of becoming infected
• once infected, more rapid progression and greater severity due to lack of immune response
• start broad spec antibiotics and start early (preferred bacteriocidal)
• always consider opportunisitic organisms
  • PCP, Cryptococcus, Aspergillus

• G6PDH deficiency can cause have hemolysis
  • sulfas, nitrofurantoin, primaquine
• rapid acetylators
  • NAT activity in liver
  • more common in Asia
  • faster acetylation of some antimicrobials (ex: INH)

• affects ability to metabolize and excrete antimicrobials
  • could have high serum/tissue conc. of drugs or metabolites are toxic
  • ex: imipeniem and seizures, aminoglycosides and neurotoxicity
• renal excretion most important route of elimination of most antimicrobial agents
  • dosage of most drugs must be reduced and given at less frequent intervals
  • ex: aminoglycosides, vancomycin, acyclovir, fluconazole

• certain antimicrobials should be used with caution in patients with impaired hepatic function
  • erythromycin
  • metronidazole
  • azoles
  • pyrazinamide
• some antimicrobials induce hepatic metabolism of other medications
  • rifampin and antiretrovirals

• inhibit via
  • macrolides
  • azoles
  • protease inhibitors
  • ciprofloxacin
• induced via:
  • rifampin/rifabutin

• effect increased by:
  • SULF-TRM
  • metronidazole
• significant increase via
  • flucanozole
  • ciprofloxacin
• levels decreased by rifampin/rifabutin

• most important criteria: effective clinical response
• factors
  • location of infection
    • longer for difficult to erradicate infections (osteomyelitis, endocarditis)
  • seriousness of infection
  • growth characteristics of organism
    • slow growing bug (treat longer)

• oral- mild infections that can be treated on outpatient basis
• parenteral (usually IV)
  • agents not absorbed in GI (ex: aminglycosides, vancomycin, imipenem)
  • nonfunctioning at GI tract
  • seirous infection
    • need high serum concentration required than can be obtained by oral admin
  • life threatening infection (fast peak)
    • once stabilized, switch to PO ASAP

• topical: skin infection
• intraperitoneal: peritonitis in CAPD patients
• intravitreal: endophthalmitis

• abscesses- require drainage
• foreign bodies- require removal to cure infection

• elevated protein
• decrease glucose
• increase neutrophils
• increase ICP

• immunocompromised
• history of CNS disease
• new onset seizures
• papilledema
• abnormal levels of consciousness
• focal neurologic deficit

• LP and cultures ASAP and before starting emperic antibiotics
• start empiric therapy +/- dexamethasone
• if CSF findings compatible with bacterial meningitis, continue antibiotics
  • if CSF gram stain positive, targeted antimicrobials
  • if CSF gram stain negative, conitnue empiric therapy

• evidence of benefit in kids with pneumococcal meningits
• recommended to give 2-4 days of dexamethosone if:
  • known or suspected Hib in kids
  • known or suspected pneumococcal meningitis in adults
• first dose before antibiotic dose (15-20 minutes)

• for nonpregnant, adult females
  • empiric tx can be given for symptoms with or without urine dipstick test
• males and children should always have a urine culture and be investigated for UT abnormalities
  • tx should target isolated bacteria
• complicated pts
  • urinary catheterization
  • renal transplantation
  • known urologic abnormalities

• singe dose antibiotic less effect
• 3 day tx usually adequate
  • SULF-TRM
  • fluroquinones
  • trimethoprim alone
• alternative: nitrofuratoin, fosfomycin
• 3 day tx with beta lactam adequate

• urine culture recommended
• longer duration of treatment than cystitis
  • 14 days of recommended
• for adult nonpregnant women
• mild pyelonephritis
  • low grade fever with no N/V and slightly elevated WBC count
  • can tx with oral antibiotic
    • fluoroquinolones unless known susceptibility to SULF-TRM

• high fever, high WBC, vomitting, dehydration, evidence of sepsis
• admit to hospital
• tx with IV antibiotics
  • fluoroquinolone
  • aminoglycoside
  • third generation cephalosporins
• after clinical improvement (48-72 hrs), switch to oral agents active against infecting organism

• apply to nonimmunocompromised patients
  • not for hospitalized, nonambulatory residents, nursing home/LTC facilities
• CXR to confirm
• establish microbiological dx (optional)
• consider additional testing in hospitalized pts:
  • blood cultures (before starting antibiotics)
  • sputum gram stains and culture
  • urine Ag tests for pneumococcus and Legionella

• common
  • Strept pneumo
  • Hib
  • Mycoplasma
  • Chlamydophilia
  • Legionella
  • S aureus (during influenza outbreaks)
• less common
  • COPD- Moroxella
  • chronic inhaled steroids, alcoholics, COPD- gram negative bacteria
• virus- RSV, influenza, adenovirus, parainfluenza

• target bacteria unless suspect influenza
• outpt management
  • previously healthy, no antibiotics use for past 3 months (ex: low risk of resistant bug)
    • oral macrolide preferred
    • oral doxocyclin
  • comorbidities or use of antibiotics in the past 3 months
    • respiratory quinolones
    • beta lactam and macrolide
      • high dose amoxicillin
      • cetriaxone, cefpodoxime, cefuroxime

• respiratory quinolone
• beta lactam and macrolide
  • high dose amoxiciloin or amox/clavulanate
  • cetriaxone, cefotaxime, cefuroxime
• usually start with IV and switch to PO when improving

• if start on IV antibiotics, switch to oral as soon as hemodynamically stable, are improving clinically and are able to take PO meds
• in general, tx for at least 5 days with appropriate antibiotics
  • should be
    • afebrile for at least 48-72 hrs
    • without signs of clinical instability
• most CAP are treated for 7-10 days