• Use only when needed (or at least when benefit exceeds risk).
• Use in conjunction with other management strategies.
• Use rapid tests, culture and susceptibility results to guide therapy.
• Consider the site, causative agent and seriousness of infection.
• Consider route of administration and frequency of dosing.
• Consider all underlying illnesses and drug allergies.
• Choose the least toxic agent.
• After all other considerations, consider cost.
• Follow-up with patient to determine drug efficacy and safety.

1. First generation (natural and antistaphylococcal penicillins)
   • Penicillin G (aqueous, procaine, benzathine), phenoxymethylpenicillin (penicillin V), methicillin, oxacillin, dicloxacillin, nafcillin.
   • Comments
     • Pen G and V are useful against streptococci, most anaerobes found in the oral cavity, Treponema pallidum, Clostridium, non-penicillinase producing staphylococci, most Neisseria and Bacteroides sp. (except B. fragilis), Listeria and Pasteurella multocida.
     • Methicillin, nafcillin, oxacillin, and dicloxacillin are effective against penicillinase-producing strains of S. aureus.

2. Second generation (aminopenicillins)
   • Ampicillin and amoxycillin.
   • Comments
     • Broader spectrum against G- organisms (E. coli, P. mirabilis and H. influenzae).
     • Ineffective against penicillinase producing bacteria, Klebsiellla and Pseudomonas strains.
     • Drugs of choice against Listeria.
     • E. coli and H. influenzae are showing increasing resistance to these agaents.

3. Third generation (carboxypenicillins)
   • Carbenicillin and ticarcillin.
   • Comments
     • Increased activity against P. aeruginosa, Enterobacter sp., Morganella morgagni and Proteus sp.
     • Ineffective against penicillinase producing bacteria.
     • Less effective against enterococci than is ampicillin.
     • Often used in combination with an aminoglykoside to treat P. aeruginosa infections.

4. Fourth generation (ureidopenicillins)
   • Azlocillin, mezlocillin and piperacillin.
   • Comments.
     • Broader spectrum of activity than third generation penicillins.
     • More activity against enterococci.
     • Greater activity against P. aeruginosa and Klebsiella strains.
     • Inactive penicillinase-producing staphylococci or ampicillin-resistant H. influenzae.

• Clavulanic acid + ticarcillin = TIMENTIN
• Clavulanic acid + amoxycillin = AUGMENTIN
• Sulbactam + ampicillin = UNASYN
• Tazobactam + piperacillin = TAZOCIN

1. 1^st generation
   Excellent broad-spectrum activity against G+cocci (S. aureus, S. pneumoniae), limited activity against G- bacilli except E. coli, P. mirabilis and Klebsiella. Poor coverage of pneumococcus. Cefazolin is useful in surgical profylaxis and treatment of uncomplicated soft tissue infections.

2. 2^nd generation
   more efective against G-bacilli than 1st generation.
   • Cefoxitin and cefotetan have excellent activity against B. fragilis and Serratia sp.
   • Cefuroxime crosses the blood-brain barrier (useful in treatment of some forms of bacterial meningitis: H. influenzae, S. pneumoniae, N. meningitidis in high doses).

3. 3^rd generation
   Broader activity against most enteric G-bacilli but less activity against S. aureus.
   • Cefotaxime and ceftriaxone demonstrate good cerebrospinal fluid penetration and are useful in the treatment of pneumococcal infections, H. influenzae and N. meningitidis meningitis.
   • Ceftazidime is active against P. aeruginosa.

4. 4^th generation
   Cefepime (MAXIPIME) is effective in the treatment of infections caused by P. aeruginosa and other highly resistant G- bacilli. It is useful in the treatment of nosocomial pneumonia.

1. Currently available agents are imipenem-cilastin (PRIMAXIN) and meropenem (MERREM, MERONEM).
2. They provide broad G+ and G-, aerobic and anaerobic coverage. Meropenem is slightly more active against G- organisms, whereas imipenem is a little more active against G+ organisms.
3. Inadequate coverage of methicillin-resistant S. aureus (MRSA), methiciliin-resistant S. epidermidis (MRSE), Enterococcus faecium and Xanthomonas maltophilia. Emergence of Pseudomonas resistant to these antibiotics has been reported.
4. Meropenem is less likely to cause seizures (can be used for meningitis) and is also approved for intraabdominal infections.
5. Both antibiotics can be used for treatment of hospital-acquired infections that may be resistant to other antibiotics.

1. Include aztreonam.
2. Used against all gram-negatives.
3. Resistant to all known beta-lactamases.

1. Common preparations: Gentamicin, tobramicin, amikacin, kanamicin, neomycin, netilmicin and streptomycin.
2. Comments:
   • Aminoglycosides have excellent activity against aerobic G- rods, however they are ineffective against anaerobic organisms and streptococci.
   • Amikacin has the broadest spectrum of activity, it is useful in the treatment of genta- and tobramycin resistant bacteria and in the treatment of infections caused by susceptible Nocardia and non-tuberculous mycobacteria.
   • Netilmicin has a coverage spectrum similar to gentamicin but is less nefro- and ototoxic.
   • Kanamycin is infrequently used because of high degree of bacterial resistance.
   • Neomycin is used orally to reduce intestinal bacteria in patients with hepatic encefalopathy and for preoperative sterilisation of the aerobic gut flora, however, even negligible gastrointestinal (GI) absorption may cause toxicity in patients with renal failure.
   • Gentamicin and generic tobramycin are the drugs of choice against sensitive strains because of their lower cost and extensive clinical experience.
   • Streptomycin is used primarily in multidrug-resistant TB.

1. Erythromycin
   • Active against most gram-positive cocci, however, not bactericidal and not first line therapy for S. aureus.
   • Effective against M. pneumoniae, Legionella sp., pneumococci, group A streptococci, Chlamydia and Campylobacter jejuni.
   • Inactive against most G- bacilli.
   • Other disadvantages: common GI side effects, drug interactions and short life requiring frequent dose administration.

2. Azitromycin (ZITHROMAX, SUMAMED) and Claritromycin (BIAXIN, KLACID).
   • Both drugs are more active than erythromycin against specific gram negative pathogens, including H. influenzae and Moraxella catarrhalis, making them useful in acute exacerbations of chronic bronchitis and for ambulatory treatment of community acquired pneumonia.
   • Good tolerance profiles (decreased incidence of GI side effects) and easy to administer (once a day dosage).
   • Azithromycin is also useful as a single dose therapy (1g) against uncomplicated nongonococcal urethritis caused by Chlamydia trachomatis, it is effective in community acquired pneumonia and can be administered IV to hospitalized patients. It is also effective in skin and soft tissue infections.
   • Clarithromycin is the most effective Mycobacterium avium complex (MAC) antimicrobial agent and is used for treating active MAC disease in patients with or without AIDS, it is also effective against H. pylori infection.
   • Disadvantages: both drugs are much more expensive than erythromycin. Clarithromycin, like erythromycin, may inhibit hepatic cytochrome P-450 enzyme (decreased clearence of theophylline, carbamazepine, etc). Of concern is also the increasing resistence of S. pneumoniae, H. influenzae and group A streptococci to these agents.

1. Include clindamycin (DALACIN) and lincomycin
2. General characteristics:
   • Activity spectrum similar to erythromycin in addition to full anaerobic coverage except for Clostridium, Legionella and Mycoplasma
   • Lincomycin - the drug of choice for osteomyelitis.
   • Clindamycin and lincomycin can cause pseudomembranous colitis.

• Useful in the treatment of typhoid fever, CNS infections, intraocular infections, anaerobic infections, serious rickettsial infections.
• Chloramphenicol can cause dose-related anaemia and rarely (1 : 50 000) irreversible aplastic anaemia.

1. Currently available tetracyclines are doxycycline, minocycline, demeclocycline, oxytetracycline and tetracycline.
2. Comments
   • Doxycycline is useful in the treatment of respiratory infections (acute exacerbations of chronic bronchitis, atypical pneumonia), Lyme borreliosis, rickettsioses, ehrlichiosis and genital infections (granuloma inguinale, lymfogranuloma venerum [LGV], Chlamydia trachomatis).
   • Tetracycline is effective in the treatment of H. pylori (in combination with bismuth and metronidazole or clarithromycin).
   • Minocyline is commonly used for acne vulgaris.
   • Demeclocycline inhibits antidiuretic hormone (ADH) - induced water reabsorbtion in the kidneys and is useful for treatment of syndrome of inappropriate secretion of ADH (SIADH).
   • Tetracyclines can cause photosensitivity and discoloration of developing teeth (contraindicated in pregnancy and breastfeeding and in children younger than 8 years). Hepatotoxicity can also occur, especiallly in patients with renal insufficiency.

1. Semisynthetic antibiotic derivative of rifamycin B.
2. Indicated in all forms of TB.
3. Useful to eliminate meningococci from the nasopharynx.
4. May be useful as an addition to erythromycin for poorly responsive Legionella pneumonia.

1. Active against only G+ bacteria.
2. Used primarily IV as an alternative agent in serious infections caused by G+ cocci, especially S. aureus and S. epidermidis, in penicillin-allergic patients (e.g. endocarditis). It is also useful orally in the treatment of psedomembranous colitis caused by C. difficile resistant to metronidazole.
3. Because of the emergence of vancomycin-resistant enterococci (VRE), the Center for Disease Contol (CDC) has issued the following guidelines for its use:
   A. Appropriate indications for vancomycin:
   • (1) Serious infections caused by beta-lactam-resistant G+ organisms.
   • (2) Infections caused by G+ organisms in patients with serious allergy to beta-lactams.
   • (3) Antibiotic-associated colitis that has not responded to metronidazole or that is severe and potentially life threatening.
   • (4) Prophylaxis of endocarditis in high-risk patients undergoing certain procedures (as recommended by the American Heart Association).
   • (5) Prophylaxis before surgical procedures involving implantation of a prosthetic material or device if the institution has a high rate of infection with MRSA or S. epidermidis (one dose; two doses if procedure lasts more than 6 hours).
   B. Inappropiate uses that must be discouraged:
   • (1) Routine surgical prophylaxis.
   • (2) Empiric therapy in febrile, neutropenic patients UNLESS the following holds: (a) There is strong evidence initially that the infection is caused by G+ organisms (e.g. inflamed exit site of a Hickman catheter). (b) The prevalence of infections caused by beta-lactam-resistant G+ organisms in the hospital is substantial.
   • (3) Treatment given in response to one blood culture that is positive for coagulase-negative staphylococci when other blood cultures drawn at the same time are negative (i.e. if contamination is likely).
   • (4) Continued empiric use for presumed infection after blood culture results are reported as negative for beta-lactam-resistant G+ organisms.
   • (5) Systemic or local prophylaxis for infection or colonization of indwelling or vascular grafts.
   • (6) Selective decontamination of the digestive tract.
   • (7) Eradication of colonization by MRSA.
   • (8) Primary treatment of antibiotic-associated colitis.
   • (9) Routine prophylaxis of infants with very low birth weights.
   • (10) Routine prophylaxis in patients receiving continuous ambulatory peritoneal dialysis.

• Its structure and activity are similar to those of vancomycin, but adverse reactions are milder.

1. Quinupristin/dalfopristin is approved for treatment of vancomycin-resistant enterococci (VRE).
2. It is active against vancomycin-resistant E. faecium but not E. faecalis.
3. It is available for parenteral use only.

1. Linezolid is the first of the oxazolidinone class of antibiotics. It is indicated for treatment of vancomycin-resistant E. faecium (VREF) infections, nosocomial and community-acquired pneumonia, and skin and skin-suture infections.
2. It inhibits protein synthesis at the bacterial ribosome. It is often bactericidal against streptococci and bacteriostatic against staphylococci and enterococci.
3. Unlike quinupristin/dalfopristin, it is active against both E. faecium and E. faecalis.
4. Its use should be reserved for documented VRE infections. It is available PO and IV.

1. Useful in prophylaxis and therapy of Pneumocystis carinii pneumonia (PCP).
2. Useful for treatment of outpatient urinary tract infections (UTIs)
3. Effective in otitis media and sinusitis (in penicillin-allergic patients) and in exacerbations in chronic obstructive pulmonary disease (COPD).

1. Class of antimicrobial agents structurally related to nalidixic acid (first-generatin quinolone) but with greater potency and a broader spectrum of activity; they exert their action by inhibiting bacterial DNA replication.
2. In general, quinolones are active against Enterobacteriaceae and most other G- bacilli (including P. aeruginosa); they are especally useful in treating infections of the urinary tract and some sexually transmitted diseases (STDs). They have limited activity against anaerobes and G+ bacilli; none of them have significant activity against enterococci.
3. Second generation quinolones (ciprofloxacin [CIPRINOL, CIPRO], enoxacin, lomefloxacin, ofloxacin [TARIVID, OFLOXIN] and norfloxacin) exhibit good activity against G- bacilli and Legionella pneumophila, moderate activity against staphylococcal species, and weak activity against Streptococcus pneumoniae.
4. Third-generation quinolones (grepafloxacin, levofloxacin, moxifloxacin, gatifloxacin [TEQUIN] and sparfloxacin) have expanded coverage against streptococci and atypical organisms, making them useful in community acquired pneumonia, acute sinusitis, and bacterial exacerbatons of acute bronchitis. Their activity against G- bacteria is weaker than that of second-generation agents.
5. Fourth-generation quinolones (trovafloxacin) have same antimicrobial spectrum as third-generation agents plus broad anaerobic coverage.
6. Concomitant administration of antacids must be avoided, since the absorbtion of all quinolones is significantly reduced by antacids that contain magnesium or aluminium; quinolones generally also interfere with theophylline metabolism (via inhibition of cytochrome P-450) and can result in theophylline toxicity.
7. NOT to be used in pregnant women or in children under 15 years.

1. Effective against anaerobes (B. fragilis, Clostridium, Fusobacterium, anaerobic cocci); useful for intraabdominal and pelvic infections.
2. Good CSF penetration; useful in the treatment of meningitis or brain abscess resulting from B. fragilis.
3. Effective in the treatment of pseudomembranous colitis resulting from C. difficile.
4. Antiprotozoal; useful for therapy for Trichomonas and Entamoeba histolytica.

Effective treatment of Pseudomonas aeruginosa infections can be achieved with a combination of an aminoglocoside AND one of the following:

1. an antipseudomonal penicillin
2. ceftazidime
3. aztreonam
4. ciprofloxacin (or other quinolones)

The most frequent b-lactamase producers are:

• Haemophilus influenzae
• S. aureus
• N. gonorrheae
• M. catarrhalis
• B. fragilis

At the present time all methicillin-resistant S. aureus are currently sensitive to vancomycin or teicoplanin therefore the agent of choice for the treatment of MRSA are those ATBs. Alternatives include TMP-SMX, clindamycin, quinolone, aminoglycoside, and rifampin. Rifampin should always be combined!

In the treatment of severe staphylococcal infections, an anti-staphylococcal penicillin should always be combined with an aminoglycoside or rifampin.

Photosensitivity: You should warn your patient not to expose itself to the sun, while taking these antimicrobials: Almost all quinolones, azithromycin, sulfonamides, tetracyclines.