- Streptococcus Viridians

- S. Aureus (MSSA)

- S. Pneumoniae

- N. Meningitis

- H. Influenzae

- S. Pneumoniae

- H. Influenzae

- Atypical Organisms

- MRSA

- Pseudomonas Aeruginosa

- Enterococcus spp.

- Enteric gram negatives

- Gram negative anaerobes

- MSSA

- Streptococcus spp.

- Pseudomonas Aeruginosa

- MRSA

- anaerobes

- Gram negatives

- Enteric Gram negative (E. Coli)

- STD's: Neissera, Chlamydia

- Streptococcus sp.

- S. Aureus (MSSA)

- Staphylococcus Aureus (MSSA, MRSA, GISA)

- S. Pyogenes

- Streptococcus Pneumoniae (PRSP)

- Enterococcus Faecium (VRE, LR-VRE)

- Pseudomonas Aeruginosa

- Acinetobacter

- Klebseilla

- E. Coli

- Enterobacter

- Citrobacter

- Serratia

- Proteus

- No Enterococcus spp. coverage

- Dosed less frequently

- Some MSSA activity, a little bit of gram (-), NO CNS PENETRATION in this gen.

- 2nd Gen, Zo likes to SEW during surgeries

- Cefuroxime ROX skin infections

- In 3rd gen, Tax and Triax are very taxing on Strep Pneumoniae

Ceftriaxone: Dosed q24 hours, q12 hours in CNS infection

Cefotaxime: Older, dosed q8 hours

Both have S. Aureus coverage

- They are PRIME when it comes to Pseudomonas coverage.  

- No reliable staph coverage

- Cefepime dosed BID, 2g IV q8h for Pseudomonas

- Extremely broad spectrum

- Covers MSSA, B. Fragilis, and Pseudomonas

- Does NOT cover Corynebacterium jeikieum and Stenotrophomonas

- Coformulated with Cilastatin (inhibits dehydropeptidase-1), to decrease nephrotoxic metabolites

- Of the three, Imipenem has highest incidence of seizures (1.5%).

-Risk factors are old age, renal problems, and history of seizures

- Dosed q6-8h, unless renal problems

- Once-a-day Carbapenem

- 1g q24 hours

- Broad spectrum, but not for pseudomonas or enterococcus

- For intra-abdominal and skin infections

- No inhibition of P450 system or glycoprotein transport.

- Dosage adjustment if clearance <30, T 1/2 = 4 hours

- Only effective against gram negatives

- Good for Pseudomonas

- NOT equivalent to Gentamycin

- No synergy, no effect on gram positives or mycobacteria

Azactam is EXACT only against gram negatives

Type I - Immediate Hypersensitivty

Type II - Cytotoxic antibodies, IgG, IgM bind to renal/blood cells

Type III - Immune complexes, IgG and IgM bind to circulating antigens, serum sickness, 7-14 days after initiation

Type IV - Cell mediated, T-cell dependent, WBC recruitmant leading to inflammation, dermatitis.  

- Stevens-Johnson syndrome

- Toxic Epidermal Necrolysis

- Multi-Organ involvement

-Happens in 10% of population, rash in 1-3%, skin test can detect it in 60% of cases

- 20% of pop. always colonized, 60% intermittent carriers, and 20% never carry the organism

- MRSA emerging b/c of acquisition of mecA gene that encodes PBP2 (CA-MRSA emerged differently)

- multiple virulence factors

- Vancomycin drug of choice

Glycopeptide-Intermediate Staph Aureus and Glycopeptide Resistant Staph. Aureus

Higher doses of Vancomycin don't necessarily help, but they do INCREASE toxicity....this is bad

- S. Epidermidis, S. Saprophiticus, S. Hemoliticus, S. Luteus

- Vancomycin is drug of choice

- Normal gut flora, either in the form E. Faecalis (90%), or E. Faecium (10%)

- Multidrug resistant strains are emerging from E. Faecium and are referred to as VRE

- Powerful gram positive coverage for resistant organisms

- Not as effective as anti-staphylococcal penicillins

- Potential to select for VRE

- Oral agent for C. Difficile

- Dosed 1g IV q8-12h or 15mg/kg IV q12h

- Approved for Vancomycin resistant E. Faecium

- Active against MRSA, MSSE, Streptococci spp.

- Only mix with D5W

- Monitor for myalgia and arthralgia, may cause increase in LFT's.

- 7.5mg/kg q8h, no renal issues, does not penetrate CNS

- Serotonin Syndrome

- Thrombocytopenia and anemia

- Creates channels that rapidly depolarize the bacterial membrane.  Rapidly bacteriacidal

- Active against MRSA, VRE

- Gram positive organisms only

- 4-6 mg/kg qd

- Skin and skin structure infections

- Skeletal muscle toxicity

- Drug class Glycylcycline, which are Tetracycline analogs

- Activity against multi-drug resistant acinetobacter spp.

- Evades Tet (A-E,K) efflux pumps

 - Not active against MDR effluxes, which are in Pseudonomas and Proteus

- 100mg x 1 dose, then 50mg IV q12h

- Activity like Cefepime but also covers MRSA

- Very active against Pseudonomas, action goes A > T> G

- Need aerobic environment for uptake

- Excellent in sepsis

Never monotherapy except for UTI

- Nephrotoxic in eldery, dehydration, long therapy, and concomittant NSAIDS, Cyclosporine, Vancomcyin, amphoterericin B, Furosemide

- Vestibular and auditory ototoxicity

- Similar gram negative coverage

- Levofloxacin biggest spectrum, improved gram positive coverage

- Indicated for Staph and Pseudonomas

- Cover atypicals such as Mycoplasma, Chlamydia, Ricketssia, Legionela

- Cipro for res. UTI, infectious diarrhea, dosed BID.  Levo dosed once a day, used for MDR TB.  

- Primary side effects tendinitis and tendon rupture, cipro least likely for QT problems, Gatifloxacin most likely for blood sugar problems

- Chlamydia

- Mycoplasma (M. Pneumonia, M. Hominis, M. Feremetans)

- Legionella (severe L. Pneumophila)

- Rickettsia

- All have P450 interactions with the exception of Azithromycin

- In terms of dosing, goes E -> C -> A (A is dosed once a day)

- 

- 60 hours half-life

- Gram (+), so Strep.  Throat

- Not for UTI's, but OK for STD's

- 2gm po for GC

- 1gm po for chlamydia

- Doxycycline used for CAP and some atypicals

- Minocycline used for acne

- Gram (-) anaerobic activity

- Drug of choice for C. Difficile

- Metalic taste, peripheral neuropathy, avoid alcohol.

- Lincosamide

- Gram (-) anaerobe activity

- Decent for MSSA and MRSA

- can lead to pseudomembranous collitis

- Excellent bone, but NOT CNS, penetration

- Broad Spectrum

- Good with MRSA

- OK for second trimester

- Best prophylaxis for PCP (Pneumocystic something Pneumonia) and Toxoplasmosis

- Cheap

- Only for UTI's

- Includes VRE-cystitis, urethritis

- Contraindicated at 38-42 weeks gestation

- Precautions in lung problems, peripheral neuropathy, and false positive urine glucose tests

- Polymixin E either IV or inhalation

- For managing multi-resistant Pseudomonas

- For cystic fibrosis patients

- 1 Mu (33mg) by neb. bid x 90 days

- Nephrotoxicity associated with IV route 

- Single 3 gram dose to be dissolved in water

- Preg. category B

- Broad spectrum and good with certain strains of Pseudomonas

- Time course of an antimicrobial therapy

- Rate of bacterial kill

- Dose-kill response relationship

- Post-Antibiotic Effect

Fluoroquinolones and Aminoglycosides - Concentration dependent, maximize exposure

Carbapenems, Cephalosporins, and Penicillins - Time dependent, optimize duration of exposure

- Increase dosing frequency (shorten interval)

- Increase duration of infusion

- Select agent with lower MIC's

1.  Typically used in combination with other gram (-) and gram (+) antibiotics

2.  Dosing intervals are depedent on renal function

3.  Nephrotoxicity typically increases after 5 days of therapy

4.  Renal function is confounded by age, weight, Scr when using Cockcroft-Gault

5.  Aminoglycoside PK are highly variable

6.  Blood samples for concentration determination must be drawn post-distribution

7.  TD means low peak concentrations and detectable troughs

8.  HDODA refers to relatively high peak concentrations and undetectable concentrations after 24h

Ke = CL/Vd

 Vd = 0.3 L/kg (IBW) + 1 L/kg

Complete the following calculations: IBW, TBW, CL, Vd, and T 1/2.

Patient: 73 yo male, SCr= 1.4 mg/dL, 5’8”, 180 lbs

- PAE of 1-8 hours for Pseudonomas and most enterobacteria

- Enhanced by Beta-Lactam drugs

- Enhanced by high concentration and long exposure

- PAE tends to be shorter in neutropenic animal models

- Minimal PAE against Gram (+)

- Transient, reversible resistance that develops within 1-2 hours after dosing and disappears within 8 hours after removal of antibiotic

- Results from down-regulation of aminoglycoside uptake during the rapid energy-dependent phase of drug uptake (EDP-II)

Toxicities: Nephrotoxicity, Ototoxicity, Neuromuscular Blockade

Strategies: HDODA dosing, reduces nephrotoxicity.  For Ototoxicity, immediately stop therapy.  Give HDODA over 1 hour of infusion to reduce neuromuscular blockade, and treat with IV Calcium Gluconate.

- Clearance of < 40ml/min

- Enterococcus Infections

- Spinal Cord Injury

- Burn patients

- Meningitis

HDODA: 4-7 mg/kg

TD: 1-2 mg/kg

- Draw levels after steady state (4-5 Half-lives or 3rd dose)

- Draw levels 1 hour after end of infusion (peak) and prior to next dose (trough)

- If peak is too high, reduce the dose, if trough is too high, reduce the interval

- Levels should be drawn off the first dose, steady state will not be achieved in this case

- Levels should be drawn >2 hours after end of infusion (alpha phase)

- Second level should be drawn 10-12 hours after end of infusion

- Levels do NOT reflect peak and trough (must be extrapolated)

Not unless..........

-Scr increases by >0.5mg/dl or 50% from baseline

- Last levels are obtained >7 days

- Patient's dynamic status is constantly changing

What is Peak a good predictor of?

What is Trough a good predictor of?

(for Aminoglycoside therapy)

Peak: Efficacy

Troughs: Renal Toxicity

- Used orally for Clostridium Difficile infections

- Abs. not clinically significant in most cases

- More significant with prolonged therapy and reduced kidney function

Alpha phase - 0.5-1 hour

Beta Phase - 2-20 hours

- The alpha phase can be further prolonged with renal failure, and thus makes it hard to find a true peak. 

- The Vd varies from 0.5-1 L/kg, with the average being 0.7 L/kg. 

- There is poor distribution to the CNS and bone matrix, and protein binding varies from 10-80%

- Small % is metabolized, ~7%

- Vancomycin is both filtered and secreted renally. 

- As renal function deteriorates, Vancomycin clearance decreases

- Concentration dependent killing, maxed at 4 x MIC

- PAE minimal

- Slowly bactericidal

- AUC/MIC  ratio of 400

- Vancomycin nephrotoxicty was considered to be infrequent and reversible

- Co-administration with aminoglycosides could increase risk of nephrotoxicity

- No CLEAR relationship between exposure and nephrotoxicity

15 mg/kg IV q12 hours

Aim for trough concentrations of 15-20 mcg/ml

- Vancomycin does not penetrate well into lung tissue

- 1g dose of Vancomycin does not achieve sustained lung concentrations > MIC for suscpetible staphlococci over a 12h dosing interval

- Recent guidelines recommend trough concentrations of 15-20 mg/L

- This has been adopted by many clinicians, irrespective of infection source

- Toxicity is unknown, but recent studies show a strong correlation between higher  trough correlations and nephrotoxicity

- No ototoxicity in animal models

- Confounding factors, Mississippi Mud formulation, and limited serum data leads to unreliable data in human studies

- Does appear to increase risk when added to aminoglycosides

- Vd and Cl is highly variable, even in healthy patients.

- In those with altered renal function, volume status, or the morbidly obese, the parameters are even more variable

- Infuse slowly over 1 hour to reduce the incidence of redman syndrome

- Peaks not necessary to monitor

- Maintain trough levels of 10-20 mg/L (according to the 15-20 mg/L principle)

- Sample blood 1 hour or less before next dose (which would be the trough)

- Use the Vancomycin nomogram to find the dose

- If clearance or weight is in between boxes, round

- If a patient's Cl < 30 ml/min, do 1 x 20mg/kg dose, then check a random level in 48 hours

- Redose when levels are below 15 mcg/ml (or 15 mg/L)

- Staph. Epidermis

- Staph. Aureus

- Streptococcus spp.

Enterobacteriaceae

- Corynebacterium spp.

- Propionbacterium spp.

- Peptostreptococcus spp.

- Bacillus spp.

- Micrococcus spp.

*BMC PP

- Pityrosporum ovale

- Candida spp.

Face and neck have highest bacterial density, which is Staph. Epidermis.

The groin area and other moist regions are mostly colonized by gram negative bacilli

Primary - Single pathogen, area of previously healthy skin

Secondary - Polymicrobial, previously damaged skin

- Erysipelas

- Impetigo

- Lymphangitis

- Cellulitis

- Necrotizing Fascitiis Type I and II

*LICEN (Underworld anyone?)

- Diabetic Foot Infections

- Pressure Sores

- Bite wounds, both animal and human

GAS by itself - Erysipelas, Type II Necrotizing Fascitiis

GAS/S. Aureus - Impetigo, Lymphangitis, Cellulitis

Anaerobes/GAS - Type I Necrotizing Fascitiis

S. Aureus and Streptococci are found in both.  The differences......

Animal Bite - Pasteurella Multocida, Bacteroids spp. (We pasteurize animal milk to get rid of bacteria I guess)

Human Bite - Eikenella Corrodens, Corynebacterium spp., anaerobes (Eiks! Cory bit Anna!)

- St. Anthony's fire

- Superficial cellulitis with lymphatic involvement

 - Effects infants, young children, elderly, those with nephrotic syndrome

- Usually lower extremities and face

- Caused by GAS (Strep. Pyogenes)

- Bright red lesion, edematous, indurated (hardened), painful, accompanied by fever and leukocytosis

- Penicillin VK 500mg q6h x 7-10 days

- If serious, use Penicillin G

- If allergic rxn, use erythromycin

- Infection of  the epidermis and dermis, may spread to superficial fascia

- Inflammation with little or no necrosis

- Caused by GAS/S. Aureus, H. Influenzae in infants, GBS in newborns, S. Epidermidis in immunocompromised pts.

- Erythema and edema of the skin (painful, hot, poorly defined)

- Lymphadenopathy

- Malaise, fever, chills

- Elevated WBC

- H/O minor trauma/abrasion

- Bacteremia (30%)

- Abscess

- Thrombophlebitis

- Septic Arthritis

- Osteomyelitis

*You'll go BATSO with all the complications

- Elevation, immobilization

- Cool saline dressings and moist heat

- Dicloxacillin 500 mg po q6h

- Cephalexin 500mg PO QID

- Erythromycin 500 mg po q6h

- Azithromycin 500 mg PO QD

- Clarithromycin 500 mg po q12h

- Amoxicillin/clavulanate 875/125 mg po bid or 500/125 mg po tid

- Nafcillin/Oxacillin IV 2g q4h

- Cefazolin 2g IV q8h

Often, Cellulitis can progress to a polymicrobial infection if the patient is diabetic, or if surgical wounds are involved.  If this were a mild case, which regimen would we use?

- Amoxicillin/Clav or...

- Fluoroquinolone (Levo, Moxi, Gati, Cipro) + Clindamycin or Metronidazole

- Ampicillin combined with Gentamycin, Clindamycin, or metronidazole

- Imipenem or Meropenem

- Ampicillin/Sulbactam

- Piperacillin/Tazobactam

- FQ with Clindamycin or metronidazole

- Highly lethal infection!

- Can occur on abdomen, perineum, or lower extremities

- Diabetes, local trauma or infection, and recent surgery are all predisposing factors

Type I - Slow onset, post surgery/trauma, gas gangrene

Type II - Flesh eating, rapid spread to severe sepsis

- Surgery!

- If Type I.......

1.  Ampicillin combined with gentamycin, clindamycin, or metronidazole

2.  Imipenem or Meropenem

3.  Ampicillin/Sulbactam

4.  Piperacillin/Tazobactam

5.  Fluoroquinolones with clindamycin or metronidazole

- If Type II......

1.  Penicillin or Nafcillin/Oxacillin with or without Clindamycin

- 20% of all diabetic hospitalizations

- 25% of all diabetics will experience a significant soft tissue infection

- 50% of all non-trauma related amputations

- Predisposing factors include: Neuropathy, PVD, Immunologic effects

- Clinical s/s may NOT be present

- Osteomyelitis could result in 30-40% of the infections

- Could present as deep abscesses (arch of foot or on toes), cellulitis of dorsum (top of foot), or Mal perforans ulcers (sole of foot)

- Could lead to necrotizing cellulitis

- Must cover gram (+), gram (-), and anaerobes!

- Surgery is often required

- Mild, superficial lesions (10%) of cases, only have minimal drainaged and gangrene.  So an oral agent can be used

- 90% of cases, which are severe, and have systemic symptoms, require IV drugs

- Clindamycin 300mg QID

- Cephalexin 500mg QID

- Amox/Clav 500/125 q8h or higher strength q12h

- Fluoroquinolones can be used, but should be combined with clindamycin or metronidazole

- Ampicillin/Sulbactam

- Piperacillin/Tazo

- Clindamycin with a gram (-) drug (3rd gen. Ceph, FQ, or Aztreonam)

- Any of the above plus Vancomycin

- Imipenem

- Meropenem

- Piperacillin/Tazo

- Any of the above plus Vancomycin

- Hematogenous (Bloodstream)

- Contiguous (Adjoining soft-tissue) through direct innoculation, trauma, puncture wounds, etc.

- Vascular insufficiency

- Additionally, the disease can be either acute or chronic

< 1 --> Long bones and Joints --> Prematurity, umbilical catheter/venous cutdown, ARDS

1-20 --> Long bones (Femur, Tibia, Mandible) --> Respiratory infection, sickle cell disease, puncture wounds to feet

>50 --> Vertebrae --> DM, blunt trauma to spine, UTI

- Direct entrance of organisms from a source outside the body

- Progressive spread of an infection from tissue to adjacent bone (fingers, toes, jaw)

- Most common in adults > 50 with predisposing factors such as PVD, atherosclerossis, DM

- Most common cause is S. Aureus

- Vascular insuffiencies could lead to polymicrobial infections, in which case Gram (-) bacilii, Pseudomonas, anaerobes, and Gram (+) could all be involved

- Tenderness of the infected area

- Pain and swelling

- Fever and chills

- Decrease motion

- Malaise

- Non-specific symptoms

- Back pain

- Fever or night sweats

- Low-grade fever

- Dependent upon precipitating cause

- Pain at infected area

- Systemic manifestations (fever, leukocytosis)

- Localized tenderness

- Warmth and edema

- Erythema over the infection site

- Nothing, if done within 10-14 days of the onset of infection

- 50% of the bone matrix must be removed before the lesions can even be detected

- If a bone or CT scan is done, it can be detected 1 day after the onset of infection

Specimen from undrained or unopened wound abscess

Anything from an open would or draining sinus would be contaminated

- Surgical debridement and drainage to get rid of reservoirs

- Start ASAP

- Maximize bone penetration

- Prolong duration, 4-6 weeks in most cases

Pathogen:  S. Aureus, Streptococcus, E. Coli

Treatment:  Semi-synthetic penicillin plus aminoglycoside or cefotaxime

Pathogen:  S. Aureus, HIB, Streptococci

Treatment:  Cefuroxime (not vaccinated against HIB), semi-synthetic penicillin, or cefazolin

Pathogen:  S. Aureus

Infection:  Cefazolin or semi-synthetic penicillin (nafcillin)

Pathogen:  S. Aureus, Pseudomonas

Treatment:  Cefazolin or semi-symthetic penicillin PLUS ceftazidime or Piperacillin/Tazo

Pathogen:  GPC, GNB, maybe anaerobes

Treatment:  Cefazolin or semi-synthetic penicillin plus Clindamycin, plus Ceftazidime or Piperacillin/Tazo

- Confirmed Osteomyelitis

- Organism identified and sensitivities determined

- suitable oral agent available

- compliance assured

Suitable Candidates:  Children (penicillinase resistant penicillins, cephalosporins, clindamycin); Adults w/o DM or PVD (Gram (-) osteomyelitis, cipro or levo preferred)

- Monoarticular vs. Polyarticular joint involvement

- Hematogenous (most common), contiguous, and direct innoculation mechanisms

- Mostly in patients > 16 years of age

- Deep penetrating wound

- Intra-articular injections

- Arthroscopy

- Prosthetic joint surgery

- Contiguous Osteomyelitis

Most common - S. Aureus

Less Common - E. Coli, Streptococcus

Sexually active - N. Gonorrhoeae

IVDU - S. Aureus and Pseudomonas

Neonatal - S. Aureus, Streptococcus, Gram (-), H. Influenzae Type B

- Single joint involvement of knee, shoulder, wrist, hip, ankle, elbow

- S/S include fever, elevated WBC, Hot swollen joint

- Initial synovial WBC count is > 100,000

- Blood culture is + >50%

- Migratory Polyarthralgia

- Fever

- Dermatitis (small papules on trunk/extremities)

- Tenosynovitis (inflammation of the tendon sheath)

- 30-40% present with hot, swollen, purulent joint (Initial synovial WBC count <50,000)

- Elevated ESR and WBC

- Aspiration of joint fluid yields WBC count between 50-200k, low glucose (<40mg/dL)

- Gram stain and culture of synovial fluid (Non-gonococcal >> gonococcal)

- Blood cultures ( " ")

- If gonococcal --> Ceftriaxone 1g IV qd x 7-10 days

- If non-gonococcal, exact same treatment as osteomyelitis, depending on organism

- Joint drainage daily for 5-7 days (open drainage?)

- Joint rest

SIRS stands for Systemic Inflammatory Response Syndrome and has multiple characteristics including......

- T > 38 Celsius (100.4F) or <36 Celsius (96.8F)

- HR > 90 beats/min

- RR > 20 breaths/min or PaCO2 < 32 torr

- WBC > 12,000 cells/mm3, <4,000 cells/mm3, or 10% immature (band?)

Sepsis with signs of organ dysfunction in 1 or more of the following systems:

- Cardiovascular

- Renal

- Respiratory

- Hepatic

- Hemostasis

- CNS

- Unexplained metabolic acidosis

- Tissue injury

- Malignancy

- Neurologic injury

- Metabolic abnormalities

- Therapy (?)

- 90% bacterial in origin

- Gram (+): S. Aureus, S. Epidermis, S. pneumoniae, E. Faecalis

- Gram (-): E. Coli, Klebsiella, Pseudomonas

- Other causes, such as fungi

- Organism only identified in ~ 50% of cases

- Fever or hypothermia

- Rigor, chills

- Tachypnea

- N/V

- Hyperglycemia

- Myalgias

- Proteinuria

- Hypoxia

- Leukocytosis

- Hyperbilirubinemia

- Lactic Acidosis

- Oliguria

- Leukopenia

- DIC

- Myocardial depression

- Pulmonary edema

- Hypotentension (shock)

- Azotemia

- Thrombocytopenia

- ARDS

- GI Hemorrhage

- Coma

Sepsis can often lead to organ failure in the following: Brain, Lungs, Kidneys, Heart, Liver, GI

What are the consequences of each?

Brain - altered mental status to coma

Lungs - respiratory stress syndrome

Kidneys - Oliguria, acute tubular necrosis

Heart - Ventricular Failure

Liver - Hepatocyte dysfunction

GI - Increased Gut Permeability

- Innapppropriate initiation of clotting

- Clotting factor and platelet consumption

- Activation of Fibrinolytic Pathways

- Hemorrhage

- Maintain vascular volume and circulation

- Support of vial organs (e.g, ventilation)

- Resolve source of infection

- Hemodynamic and physiologic monitoring

- Timely diagnosis and identification of pathogens

- Rapid elimination of the source of infection

- Early initiation of aggresive antimicrobial therapy

- Interruption of pathogenic sequence leading to septic shock

- Avoidance of organ failure 

- HPI

- PE

- Culture!!:  2 sets of Blood cultures, urine culture, sputum

- Labs:  CBC, Chemistry 7, Coagulation parameters, arterial blood gas, serum lactate

1.  Lung

2.  Bacteremia

3.  Abdominal

4.  Soft Tissue

5.  G-U

- Surgery

- Catheter or foreign body removal

- Drainage of abscess

- Debridement of dead/necrotic tissue

- Broad

- Prompt

- Maximize Pharmacodynamics:  Enhance killing and likelihood of positive outcome, minimize potential for toxicity, prevent development of resistance

*Delayed treatment has been linked with higher incidence of mortality

CA:  Cipro or Levo

HA:  3rd Gen celphalosporin, Cipro, Levo

CA:  Ceftriaxone + either Clarithromycin, Azithromycin, or Fluoroquinolone (Levo, Moxi, or Gemi)

HA:  Piperacillin or Cefipime + Tobramycin or Cipro

CA:  Amp/Sulbactam, or Ciprofloxacin + Metronidazole

HA:  Piperacillin/Tazo or Carbapenem

CA:  Vancomycin or Linezolid or Daptomycin

HA:  Amp/Sulbactam or Carbapenem

- Duration is 10-14 days

- "Step Down" oral therapy

Hemodynamic:  Fluid therapy, Vasopressor Therapy, Inotropic therapy

Oxygen: Supplemental oxygen, Mechanical ventilation

Nutrional Support:  Increase protein, low carbs

- Rapid fluid resuscitation is best initial intervention

- Goal is to maximize CO by increasing LV preload through tissue perfusion

- Titrate in regards to HR, BP, Urine output

- Agents to use are isotonic crystalloids or colloids, with 0.9% NaCl most freq. used, pt. may require 10 L in first 24 hours

- Should be initiated when fluid resuscitation is inadequate

- Inotropes control cardiac output (Dobutamine and Dopamine)

- Vasopressors affect mean arterial pressure (Norepinephrine, PE, Epinephrine)

- Dopamine is a less favorable choice b/c of tachycardia, myocardial ischemia, and infarction. 

- Activated Protein C (APC)

- Anticoagulant that controls development of microthrombi

- Inactivates factors Va and VIIIa

- Enhances Fibrinolysis

- Anti-inflammatory effects

- Levels substantially decreased in sepsis

APACHE II:  25-30

APC:  23% Mortality Rate

Placebo:  39% Mortality Rate

- Mucosal Colonization of the fimbriae kind (H. Influenzae, N. Meningitidis) and polysaccharide (S. Pneumoniae)

- Survives Intravascularly, about 10³CFU/ml

- Contains antigens

- Invasion of Meningeal and subarachnoid space

- Disruption of BBB

Adults:  HA, fever, stiff neck, (nuchal rigidity), photophobia, altered mental status, obtundation, seizures, vomitting

Children:  Lethargy, confusion, somnolence

Infants:  Irritability, altered sleep, vomitting, high pitched scream, decreased oral intake

- Lumbar puncture is performed

- Flows unidirectional down the spinal cord

- Infants 50 ml, Children 100 ml, Adults 150 ml

- Normally clear, 50-60% of serum glucose, pH 7.4, and less than 5 wbc's per cubic mm

- When infected, WBC count skyrockets to 400-100,000 per cubic mm, protein is 80-500 mg/dL, glucose is less than half of serum, differential is neutrophilic

- Low molecular weight

- Non-ionized

- Low protein bound

- Lipophilic

- Ceftriaxone 2g IV q12h OR...

- Cefotaxime 2g IV q6h + Vancomycin 1g IV q12h (use when incident of penicillin resistant S. Pneumoniae is > 5%)

-  Therapy should be initiated within 30 minutes of presentation, continued for 48-72 hours

- If neonate, eldery (>60 y/o), or alcoholic, add ampicillin 2g IV q4h, as there is an increased chance of Listeria Monocytogenes

- Needs to be administered before Antibiotics

- Inhibits production of pro-inflammatory cytokines, namely TNF and IL-1

- Improves CSF parameters in bacterial meningitis

- For Pediatric patients, 0.4mg/kg q12h x 2 days (may decrease hearing loss?)

- Adult patients, 10mg q6h x 4 days (is this per kg?)

- High dose Penicillin IV Penicllin G 200k-300k u/kg/day divided q4h x 7 days

- Prophylaxis should be adminstered within 24 hours, Rifampin is drug of choice

Adults: 600mg q12 hours x 4 doses

Children 1 month -12 years: 10mg/kg q12h x 4 doses

Children < 1 month: Half of the above dose

- Gram (+) Diplococcus

- Most common cause of Meningitis in adults

- Seen commonly in children

- Treat with 3rd gen cephalosporin x 10-14 days

- Use Cefotaxime 2g q4-6h, children 200 mg/kg q6h

- Ceftriaxone 2g q12h, children 100mg/kg q12-24h

- Vancomycin if resistant to b-lactams

- Pneumovax is over age of 2

- Prevnar if under age of 2

- Gram (-) Coccobacillus

- Could manifest as a rash

- 30-40% are ampicillin resistant

- Use Ceftriaxone or Cefotaxime

- For prophylaxis for adults, 600mg qd x 4 days.  In children over 1 month, 20mg/kg/d x 4 days.  If under 1 month, half this.

- Gram (+) bacillus

- Effects neonates and immunocompromised people

- DOC is IV Ampicillin 2g q4h x 14-21 days, for adults.  Children are 200-400 mg/kg/day divided q4-6h

- Aminoglycoside 5-7 mg/kg/day x 10 days must be added to this

- IV Ceftazidime plus Gentamicin x 3 weeks if Pseudonomas present

- Adults 2g q8h

- Children 150mg/kg/day divided q8h

- A yeast

- From inhalation of spores

-

- E. Coli (85%)

- S. Saprophyticus (5-15%)

- Klebsiella Pneumonia, Proteus spp., Pseudomonas, and enterobacter (5-10%)

- E. Coli (50%)

- Klebsiella Pneumonia, Proteus spp., Pseudomonas, and enterobacter, staphylococci, enterococcus, Candida spp.

- Enterococcus Faecilis (2nd most common HA UTI pathogen)

- Dysuria

- Urgency

- Increased Frequency

- Nocturia

- Suprapubic Heaviness

- More systemic

- Includes Flank pain

- Costovertebral tenderness

- Abdominal pain

- Fever

- N/V

- Malaise

- In a symptomatic female or catheterized patient, CFU's that exceed 10² or 10³

- In an asymptomatic patient, CFU's that exceed 10⁵

- Any growth of bacteria on suprapubic catheterization in a symptomatic patient

- Most common form of UTI in women of child-bearing age or those sexually active

- Pathogen responsible is mostly E. Coli (>90%),  but can be S. Saprophyticus

- Treatment is 3 days, and is either bactrim DS BID, or Cipro (BID) or Levo (qd)250-500 mg

- Try for at least 3 days

- DOC Amoxicillin 500mg TID x 7 days, or same dose/dir. with Keflex

- Avoid Tetracyclines and FQ's

- Avoid Sulfonamides during 3rd Trimester

- Follow up should be after 1-2 weeks of therapy and during regular intervals during gestation

- Most common cause of HA infection

- Bacteria could be introduced straight into the bladder

- Should be treated as a complicated UTI

- Prevention is best way to treat

- Presence of significant bacteria in urine in absence of signs or symptoms of UTI

- 2 consecutive urine cultures must must go same organism in about 1,000 CFU/ml.

- Management in regards to age, pregnancy status, and planned urologic procedure must be taken into account

- Genital Herpes Simplex Virus (HSV)

- Syphillis

- Chlamydia Trachomatis

- Neisseria Gonorrhoeae

- HHV 1 and HHV 2

- Lesions not present in everyone

- 50% of first episode is HSV -1

- Viral becomes almost dormant at times, detection is tough

- Genital shedding always occurs

- 2 types of infection are first episode and recurrent infection, which requires episodic therapy and suppressive therapy

- First clinical episode involves multiple painful lesions, pain and discomfort shedding and sx last a while

- In recurrent episodes, symptoms are severe, shedding lasts 4 days

- Pathogen is Treponema Pallidum

- Classified as primary, secondary, latent, or tertiary.

- Primary is incubatin, secondary is 2-8 weeks, latent is 4-10 weeks, and tertiary is 10-30 years

- As syphillus progresses, it becomes more noticeable systemically

- Benzathine Penicillin G 2.4 million units IM X 1 dose

- Follow up serology for primary/secondary is quantitative nontrepenomal tests at 6 and 12 months, while for early latent a 3rd test at 24 months is added

- Benzathine Penicillin G 2.4 million units IM x 1 dose per week x 3 weeks

- Quantitative nontrepenomals test at 6, 12, and 24 months

- Aqueous procaine penicillin G 2.4 million units IM daily plus probenecid 500mg QID both x 10-14 days

- Aqueous crystalline Penicillin G 18-24 million units IV divided every 4 hours x 10-14 days

- CSF exam q6 months until normal

Primary, Secondary, Early latent - Doxy 100mg BID x 2 weeks, Tetracycline 500mg QID x 2 weeks.

If in late latent stage, give x 4 weeks

- Most frequently reporter

- Obligate intracellular parasite --> endocervical for women, urethral for men

- Sx are primarily discharge, for both genders can lead to Reiter's syndrome, Epididymitis for men and pelvic

inflammatory disease for women

- Azithromycin 1g po x 1 dose, or doxycycline 100mg bid x 7 days

- If patient pregnant, Erythromycin base 500mg QID x 7 days, or Amoxicillin 500mg TID x 7 days

- Caused by Neisseria Gonorrhoeae (gram negative diplococci)

- Same as with previous STD, urethra for men and endocervical area for women, characterized by discharge

- Treatment is Ceftriaxone 125mg IM (if pregnant also) once

- Cefixime 400mg PO once is also option

Pseudomonas Aeruginosa, Acinetobacter, Klebseilla

(Enterobacteriacea): E. Coli, Enterobacter, Citrobacter, Serratia, Proteus

- Low cost

- easy administration

- Excellent tissue penetration

- Favorable therapeutic index

- Destroyed by b-lactamases

- Besides allergic rxn, could cause neutropenia and thrombocytopenia, interstitial nephritis, autoimmune hemolytic anemia

- Effective against GAS and it's sibs, Viridians Strep., and syphillis

- Like penicillins except a little more gram (-) coverage, better at enterococcus and listeria

- Still sensitive to B-lactamases, not 100% reliable for E. Coli, Moraxella, H. Influenzae, and Gonorrhea

- Amo absorbed better than Amp, so Amo only PO while Amp is both

- Increased coverage against b-lactamase producing organisms (S. Aureus, E. Coli, Klebsiella, anaerobes, bacteroids)

- Good for polymicrobial infections

- Amp/Sul has fixed concentration of 1.5 g

- Augmentin has fixed conc. of Clav, but 250-750mg of Amox.

- Pseudonomas is particulary dangerous, grows easily, minimal nutrient requirements

- Can present as Pneumonia, UTI, Osteomyelitis, Otitis, Endocarditis

- Usually treated with two drugs

- Have extended gram (-) coverage

- Good anaerobic coverage

- Destroyed by SOME b-lactamases (H. Influenzae, M. Catarrhalis

- Less active than ampicillin against streptococcus and enterococcus

- High NA+ content can cause a TICK in patients with renal and heart problems

- Piperacillin has same G (+) coverage as Amp. 

- Both are stable for continuous confusion

- Piperacillin has the superior pseudonomas coverage

- Does not change pseudo coverage

- Increases coverage of MSSA, H. Influenze, Klebsiella, bacteroids

- Piper/Tazo is broadest spectrum

- Covers both coagulase positive and coagulase negative Staph.

- No MRSA coverage

- No dose adjustment for renal dysfunction for Nafcillin, monitor for LFT's and interstitial nephritis

- Pretty much same for Oxacillin

-

- Enzymatic inactivation

- Efflux pumps

- Changing in antibiotic binding site

- Change in permeability

- Mutations

- Acquisition of DNA elements

- Gram (-) anaerobes, such as B. Fragilis

- Gram (-) aerobes, such as H. Influenzae, M. Catarrhalis, E. Coli, Enterobacter, Klebsiella

- MSSA

- Streptococcus Pneumoniae

- Enterococcus

- MRSA