Antibacterial Agents

Bacteriostatic include clindamycin, macrocodes, sulfonamides, and tetracyclines. Most bacterial protein synthesis inhibitors are bacteriostatic except streptogramins which is bactericidal
Bactericidal include the aminoglycosides, beta-lactams, fluoroquinolones, metronidazole, most antimycobacterial agents, streptogramins, and vancomycin

Bactericidal drugs are preferred for the treatment of endocarditis and meningitis and for most infections in patients with impaired defense mechanisms, especially immunocompromised patients.

Some bactericidal agents (aminoglycosides, fluoroquinolones) cause concentration-dependent killing. Maximizing peak blood levels of such drugs increases the rate and the extent of their bactericidal effects. This is one of the factors responsible for the clinical effectiveness of high-dose, once-daily administration of aminoglycosides. Other bactericidal agents (beta-lactams, vancomycin) cause time-dependent killing. Their killing action is independent of drug concentration and continues only while blood levels are maintained above the minimal bactericidal concentration (MBC).

Inhibition of bacterial growth that continues after antibiotic blood concentrations have fallen to low levels is called the postantibiotic effect (PAE). The mechanisms of PAE are unclear but may reflect the lag time required by bacteria to synthesize new enzymes and cellular components, the possible persistence of antibiotic at the target site, or an enhanced susceptibility of bacteria to phagocytic and other defense mechanisms including postantibiotic leucocyte enhancement. PAE is another factor contributory to the effectiveness of once-daily administration of amino glycosides and may also contribute to the clinical efficacy of the fluoroquinolones.


Erythromycinclindamycin, chloramphenicol, rifampin, and ketoconazole are notable exceptions, requiring no change in dosage in renal failure

Drugs contraindicated in renal impairment include cidofovir, nalidixic acid, long-acting sulfonamides, and tetracyclines

Dosage adjustment may be needed in patients with hepatic impairment for drugs including amprenavir, chloramphenicol, clindamycinerythromycin, indinavir, metronidazole, and tigecycline.

Dialysis, especially hemodialysis, may markedly decrease the plasma levels of many antimicrobials; supplementary doses of such drugs may be required to reestablish effective plasma levels after these procedures. Drugs that are not removed from the blood by hemodialysis include amphotericin B, cefonicid, cefoperazone, ceftriaxone, erythromycin, nafcillin, tetracyclines, and vancomycin.


several drug interactions with sulfonamides are based on competition for plasma protein binding; these include excessive hypoglycemia with sulfonylureas and increased hypoprothrombinemia with warfarin

disulfiram-like reactions to ethanol occur with metronidazole, with TMP-SMZ, and with several cephalosporins

  • the use of penicillins with gentamicin in enterococcal endocarditis, 
  • the use of an extended-spectrum penicillin plus an amino glycoside in Pseudomonas aeruginosa infections, and 
  • the combined use of amphotericin B and flu cytosine in cryptococcal meningitis. 
  • Antibiotic combinations are also commonly used in the management of infections resulting from S epidermis and penicillin-resistant pneumococci (e.g., vancomycin plus rifampin). 

Several mechanisms, discussed next, may account for synergism.

a. Sequential blockade

The combined use of drugs may cause inhibition of 2 or more steps in a metabolic pathway. For example, trimethoprim and sulfamethoxazole (TMP-SMZ) block different steps in the formation of tetrahydrofolic acid.

b. Blockade of drug-inactivating enzymes

Clavulanic acid, sulbactam, and tazobactam inhibit penicillinases and are often used with penicillinase-sensitive beta-lactam drugs.

c. Enhanced drug uptake

Increased permeability to aminoglycosides after exposure of certain bacteria to cell wall-inhibiting antimicrobials (eg, beta-lactams) is thought to underlie some synergistic effects.


Cell Wall Synthesis Inhibitors: Beta-Lactam Antibiotics & Other

Bacterial Protein Synthesis Inhibitors: Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, Streptogramins, & Linezolid

  • Most of the antibiotics are bacteriostatic inhibitors of protein synthesis acting at the ribosomal level. 
  • With the exception of tetracyclines (T), the binding sites for these antibiotics are on the 50S ribosomal subunit. Chloramphenicol (C) inhibits transpeptidation (catalyzed by peptidyl transferase) by blocking the binding of the aminoacyl moiety of the charged transfer RNA (tRNA) molecule to the acceptor site on the ribosome-messenger (mRNA) complex. Thus, the peptide at the donor site cannot be transferred to its amino acid acceptor. Macrolides (M), telithromycin, and clindamycin, which share a common binding site on the 50S ribosome, also block transpeptidation. 
  • Tetracyclines bind to the 30S ribosomal subunit preventing binding of amino acid-charged tRNA to the acceptor site of the ribosome-mRNA complex.

Bacterial Protein Synthesis Inhibitors: Amino-glycosides 
Aminoglycosides are bactericidal inhibitors of protein synthesis. Their penetration through the bacterial cell envelope is partly dependent on oxygen-dependent active transport, and they have minimal activity against strict anaerobes. Aminoglycoside entry can be enhanced by cell wall synthesis inhibitors, which may be the basis of antimicrobial synergism. Inside the cell, aminoglycosides bind to the 30S ribosomal subunit and interfere with protein synthesis in at least 3 ways: (1) they block formation of the initiation complex; (2) they cause misreading of the code on the mRNA template; and (3) they inhibit translocation (reference). Aminoglycosides may also disrupt polysomal structure, resulting in nonfunctional monosomes.

Sulfonamides, Trimethoprim, & Fluoroquinolones 

Antimycobacterial Drugs

Gram Positive Organisms: 5 Major groups 
  • Beta-Lactam Antibiotics & Other Cell Wall Synthesis Inhibitors 
  • Vancomycin
  • Linezolid
  • Respiratory Fluroquinolones
  • Misc groups: Macrolides, Tetracyclins
Gram Negative Organisms : 5 groups of antibiotics
  • Penicillin / Spectrum
  • Aminoglycosides
  • Carbapenams
  • Fluroquinolones
  • Aztreonam 
Anaerobic Organisms: 5 antibiotics
  • Clindamycin
    • Also, binds toxins 
  • Metronidazole
  • Piperacillin-Tazobactum; Ampicillin-Sulbactum
  • Carbapenams
  • Moxifloxacin
Pulmonary Infection and Antibiotics

GI Infection and Antibiotics

C. DIFF COLITIS - NAP1/BI/027 or not - Initial episode / 1st or 2nd recurrence -  Mild / Moderate / Severe / Severe Complicated - Improving / Worsening - Treatment plan
  • Recurrence Rate:
    • First Recurrence: 25 % with Metronidazole, and Vancomycin; 15 % with Fidaxomicin
    • Subsequent recurrence: 
      • 65 % following standard therapy with Metronidazole and Vancomycin
  • Metronidazole (IV) vs. Vancomycin (PO):
    • Mild to Moderate CDI treatment response rate: 98 % with Vancomycin vs 90 % with Metronidazole
    • Severe CDI treatment response rate: 97 %  with Vancomycin as  76 % with Metronidazole; this is statistically significant
Current Concepts: Clostridium difficult — More Difficult Than Ever NEJM 2008
  • Fidaxomicin (PO):
    • Initial response rate is 88 % vs 86 % in Vancomycin
    • If risk of reoccurrence is higher then Fidaxomycin is preferred BUT Do not use if NAP1/BI/027 as there is more risk of treatment failure on this strain
  • Rifaximin (PO): 
  • Probiotics: 
  • FMT (Fecal Microbiota Transplant):
  • Phamacokinetics: IDSA 2010 Guideline 
    • PO metronidazole is absorbed rapidly and almost completely, with only 6%–15% of the drug excreted in stool. Fecal concentrations of metronidazole likely reflect its secretion in the colon, and concentrations decrease rapidly after treatment of CDI is initiated: the mean concentration is 9.3 mg/g in watery stools but only 1.2 mg/g in formed stools. Metronidazole is undetectable in the stool of asymptomatic carriers of C. difficult Consequently, there is little rationale for administration of courses of metronidazole longer than 14 days, particularly if diarrhea has resolved. 
    • In contrast, vancomycin is poorly absorbed, and fecal concentrations following oral administration (at a dosage of 125 mg 4 times per day) reach very high levels: 64–760 mg/g on day 2 and 152–880 mg/g on day 4.  Doubling the dosage (250 mg 4 times per day) may result in higher fecal concentrations on day 2.  Fecal levels of vancomycin are maintained throughout the duration of treatment. Given its poor absorption, orally administered vancomycin is relatively free of systemic toxicity. IDSA 2010 Guideline

Clinical Infectious Diseases 2001;32:331–50 

Clinical Infectious Diseases 2010;50:133–64

Clinical Infectious Diseases 2010;50:133–64

Clinical Infectious Diseases 2010;50:133–64

Clinical Infectious Diseases 2010;50:133–64

C. Diff 
  1. 3-5 episodes of diarrhea of 5 days duration. Recently treated for C Diff. Concern for Mild C. Diff reoccurrence.  GDH and Toxin Negative. PCR positive for toxigenic strain. Other stool culture negative. What to do. 
    1. Treat for reoccurrence. 
    2. No treatment for C. diff.Treat with anti-diarrheal.  
      1. Answer: No treatment for C. diff at this time as it is asymptomatic carrier. Likely it is post-infectious GI diarrhea.
      2. Note: Do not do PCR if either GDH or Toxin are not positive. 
        1. Reference: CR 33, 37 of Clostridium difficile Infection NEJM 2015
  2. 37 yr old lady. C. Diff. Mild/Moderate Disease. 1st occurrence  GDH +, Toxin +, PCR NAP1/BI/027 - Negative. What abx to use to decrease reoccurrence. 
    1. PO Vanc
    2. IV Flagyl
    3. Fidoxamicin
      1. Answer: Fidoxamicin (15 % reoccurrence with Fidoxamicin vs 25 % for PO Vanc) 
      2. Note: Better resolution of diarrhea with C. Diff using PO vanco than Metronidazole even at mild / moderate illness. 
        1. Reference: Clostridium difficile Infection NEJM 2015
  3. 37 yr old lady. C. Diff.  Mild/Moderate Disease.  1st occurence. GDH +, Toxin +, PCR NAP1/BI/027 - Positive. What abx to use to decrease reoccurrence. 
    1. PO Vanc
    2. IV Flagyl
    3. Fidoxamicin
      1. Answer: PO Vancomycin (15 % reoccurrence with Fidaxomicin vs 25 % for PO Vanc is seen for non- NAP1/BI/027 strain. Among NAP1/BI/027 strain more reoccurrence with Fidaxomicin. 
      2. Note: Marked rise in Reoccurance with Flagyl on NAP1/B1/027 strain
        1. Reference: Clostridium difficile Infection NEJM 2015
KUB Infections and Antibiotics

Clinical Infectious Diseases 2011;52(5):e103–e120 

SSTI and Antibiotics

Anti-fungal Therapy

DOI: 10.1093/cid/civ482 


ATS/IDSA Guidelines for the Management of Adults with HAP, VAP, HCAP 2005
Guidelines for hospital-acquired pneumonia and health-care-associated pneumonia: a vulnerability, a pitfall, and a fatal flaw. Lancet Infect Ds 2011 

Nosocomial Meningitis Infection 

Hospital acquired Gm -ve rods 

SPACE organisms
  • Serretia
  • Pseudomonas
    • If you are covering for Psedomonas, make sure sputum culture is obtained to at least identify the organisms. 
    • Double coverage 
  • Acinetobacter 
    • Carbapenam 
  • Citrobacter
  • Enterobactareace family 
  • Chemical Pneumonitis
  • Rapid recovery in < 36 hrs. Deescalation of abx. 
  • Anaerobic Pleuropneumonia - Classic, subacute purulent cough, cavitary pneumonia with emyema. More likely to be community acquired 
  • Aspiration Pneumonia - large volume of aspiration of oropharyngeal or Gupper GI contents with a high enough PH to avoid chemical pneumonitis (when on H2 Blocker, or PPI)

Isolation in hospital 
Contact precautions: GNR with > 3 class resistance 

  • Zoster
  • RSV
Droplet Precautoin
  • Flu
  • RSV
Airborne Precaution