The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens, and inflammation all play a role. The gram-positive microaerophilic bacteria Propionibacterium acnes promote development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

The equivalence of generic drugs to their brand-name precursors continues to be controversial. The last Medical Letter review of this subject (2002) concluded that well-documented therapeutic inequivalence between brand-name and FDA-approved generic drugs had not been reported. Is that still true? New data have become available for some drugs.

Epiduo gel (Galderma), a fixed-dose combination of adapalene 0.1% (Differin), a synthetic retinoid analog, and benzoyl peroxide (BPO) 2.5%, an oxidizing agent, has been approved by the FDA for topical treatment of acne vulgaris in patients ≥12 years old.

Information about empirical treatment of bacterial infections, emerging trends in antimicrobial resistance, new drugs and new data about older drugs continue to become available. Usual pathogens and empiric treatment for some common types of infections are summarized in the text and a table listing the drugs of choice and alternatives for each pathogen begins on page 40. The recommendations made here are based on the results of susceptibility studies, clinical trials and the opinions of Medical Letter consultants.

Antimicrobial prophylaxis can decrease the incidence of infection, particularly surgical site infection, after certain procedures. Recommendations for prevention of surgical site infection are listed in this article.

The gram-positive anaerobic bacillus Clostridium difficile is the most common identifiable cause of antibiotic-associated diarrhea. The antibiotics most often implicated have been ampicillin, second and third generation cephalosporins, clindamycin and fluoroquinolones. The emergence in recent years of a new, more toxic epidemic strain (BI/NAP1), possibly related to widespread use of fluoroquinolones, has caused a marked increase in the incidence and severity of C. difficile-associated disease (CDAD).

Telithromycin (Ketek) is an oral erythromycin derivative FDA-approved for treatment of mild to moderate community-acquired pneumonia, exacerbations of chronic bronchitis and acute bacterial sinusitis (Med Lett Drugs Ther 2004; 46:66). It is generally considered an alternative antibiotic because of its cost, potential for adverse effects including visual disturbances, exacerbation of myasthenia gravis, hepatotoxicity and drug interactions. A recent report (Ann Intern Med 2006; 144:415) described serious hepatotoxicity probably related to telithromycin in three patients, including one who died and another who needed a liver transplant. Many other oral antibiotics are available for treatment of community-acquired pneumonia, exacerbations of chronic bronchitis and acute bacterial sinusitis in adults (Med Lett Drugs Ther 2005; 47:78).

Tigecycline (Tygacil - Wyeth), a derivative of minocycline, is a new intravenous (IV) antibiotic approved for treatment of complicated intra-abdominal and skin and skin-structure infections.

Gemifloxacin (Factive - Oscient), a new oral fluoroquinolone antibiotic, has been approved by the FDA for 5 days' treatment of acute bacterial exacerbations of chronic bronchitis (ABECB) and 7 days' treatment of mild to moderate community-acquired pneumonia (CAP) in adults. For the next 6-8 months it will only be available, presumably for commercial reasons, in states east of the Rocky Mountains.

Telithromycin (Ketek - Aventis) has been approved by the FDA for oral treatment of mild to moderate community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute bacterial sinusitis in patients age 18 and older. The drug is the first in a new class of antibiotics, the ketolides, derived from the macrolide erythromycin. Telithromycin has been marketed in Europe since 2001.

Antimicrobial prophylaxis can decrease the incidence of infection, particularly surgical site infection, after certain operations, but this benefit must be weighed against the risks of toxic and allergic reactions, emergence of resistant bacteria, adverse drug interactions, superinfection and cost. Medical Letter consultants generally recommend antimicrobial prophylaxis only for procedures with high infection rates, those involving implantation of prosthetic material, and those in which the consequences of infection are likely to be especially serious.

New drugs for bacterial infections and new information about older drugs continue to become available. Empirical treatment of some common bacterial infections is discussed in this article. A table listing the drugs of choice and alternatives for each pathogen begins on page 18. These recommendations are based on results of susceptibility studies, clinical trials and the opinions of Medical Letter consultants. Local resistance patterns should be taken into account. Trade names are listed on page 24.

Cefpodoxime proxetil (Vantin - Upjohn), a new third-generation oral cephalosporin, has been approved for marketing by the US Food and Drug Administration. It is available for twice-daily treatment of pharyngitis, upper and lower respiratory infections, otitis media, urinary tract infections, skin and soft tissue infections, and for single-dose treatment of uncomplicated gonorrhea in men or women and anorectal gonorrhea in women.

Enoxacin (en ox' a sin; Penetrex - Rh ne-Poulenc Rorer), a fluoroquinolone antimicrobial for oral use, has now been marketed in the USA for treatment of urinary tract infections and uncomplicated urethral or cervical gonorrhea.

Loracarbef (Lorabid - Lilly), a new beta-lactam antibiotic with antimicrobial activity similar to the second-generation cephalosporins, has been approved by the US Food and Drug Administration for treatment of respiratory, skin, and urinary tract infection caused by susceptible organisms in both adults and children. It will probably compete with drugs such as trimethoprim-sulfamethoxazole (Bactrim, Septra, and others), amoxicillin-clavulanic acid (Augmentin), cefaclor (Ceclor), cefuroxime axetil (Ceftin), and cefprozil (Cefzil - Medical Letter, 34:63, 1992).

Cefprozil (Cefzil - Bristol-Myers Squibb), a new oral second-generation cephalosporin, was recently released in the USA for treatment of pharyngitis, bronchitis, otitis media, and skin and skin-structure infections.

Temafloxacin (Omniflox - Abbott) and lomefloxacin (Maxaquin - Searle) are the latest fluoroquinolone antimicrobial agents to be approved by the US Food and Drug Administration (FDA) for oral treatment of various infections. Previously marketed include norfloxacin (Noroxin - Medical Letter, 29:25, 1987), ciprofloxacin (Cipro - Medical Letter, 30:11, 1988), and ofloxacin (Floxin - Medical Letter, 33:71, 1991). Norfloxacin is marketed only for treatment of urinary tract infections, and lomefloxacin only for treatment of urinary tract infections and bronchitis known to be caused by Haemophilus influenzae or Moraxella catarrhalis. Ciprofloxacin and ofloxacin are also available in parenteral formulations.

Since The Medical Letter last reviewed antibacterial drugs (vol.32, page 41, 1990), a few new drugs have become available, and some clinical trials of older drugs have been published. The drug of choice for treatment of an infection is usually the most active drug against the pathogenic organism or the least toxic alternative among several effective agents. Sometimes the choice of drugs is modified by the site of infection; one drug may penetrate better than another, for example, into bile, urine, or cerebrospinal fluid. The patient's clinical status may also influence the choice as, for example, when a patient has diminished renal or hepatic function, or is immunocompromised, pregnant, or allergic to penicillin. Finally, when other factors are about equal, the relative cost of the drug may be a consideration.

Clarithromycin (Biaxin - Abbott) and azithromycin (Zithromax - Pfizer), two macrolide antibiotics chemically related to erythromycin, have been approved by the US Food and Drug Administration for treatment of respiratory, skin, and skin structure infections. Azithromycin has also been approved for treatment of nongonococcal urethritis and cervicitis caused by Chlamydia trachomatis.

Ciprofloxacin, previously available orally (Cipro - Medical Letter, 30:11, 1988) and for ophthalmic use (Ciloxan - Medical Letter, 33:52, May 31, 1991), is now the first fluoroquinolone antibiotic to become available in the USA in an intravenous (IV) formulation. Cipro I.V. (Miles) is being promoted as an alternative to third-generation cephalosporins, aminoglycosides, and other drugs used for treatment of serious infections.

Ofloxacin (Floxin - McNeil, Ortho), a new fluoroquinolone antibacterial agent, was recently marketed in the USA for oral treatment of various infections caused by susceptible microorganisms. Ofloxacin is the third fluoroquinolone to become available in this country. Norfloxacin (Noroxin - Medical Letter, 29:25, 1987) is marketed only for treatment of urinary tract infections. Ciprofloxacin (Cipro - Medical Letter, 30:11, 1988), like ofloxacin, is approved for use in a variety of infections.

An ophthalmic formulation of ciprofloxacin hydrochloride (Ciloxan - Alcon), a fluoroquinolone antibiotic, was recently marketed in the USA for treatment of bacterial keratitis and conjunctivitis. Ciprofloxacin has been used orally (Cipro) to treat a variety of serious infections (Medical Letter, 30:11, 1988) and recently was approved for intravenous administration.

Since the last Medical Letter review of cephalosporin antibiotics (volume 25, page 57, 1983), many new cephalosporins have become available in the USA.

Bacterial infections of the conjunctivae are usually self-limited, but topical antimicrobial therapy can be helpful. A solution of trimethoprim sulfate 0.1% with polymyxin B sulfate 10,000 units/ml (Polytrim - Burroughs Wellcome, distributed by Allergan) was recently marketed in the USA for treatment of superficial ocular bacterial infections.

Cefmetazole sodium (Zefazone - Upjohn), a second-generation parenteral cephalosporin, was recently marketed in the USA for intravenous (IV) treatment of various infections caused by susceptible organisms. Like cefotetan (Cefotan), cefamandole (Mandol), cefoperazone (Cefobid), and moxalactam (Moxam), cefmetazole contains a methylthiotetrazole group that has been associated with prothrombin deficiency.

The gram-positive bacillus Clostridium difficile is the most common identifiable cause of antibiotic-associated diarrhea and pseudomembranous colitis (R Fekety in GL Mandell et al, eds, Principles and Practice of Infectious Diseases, 3rd ed, New York:Churchill Livingstone, 1990, page 863). C. difficile colitis usually develops during or soon after antibiotic treatment. Virtually any antimicrobial agent can cause the disorder, but clindamycin, ampicillin and the cephalosporins have been implicated most frequently. Pseudomembranous colitis was recently reported in five patients who had each taken only a single dose of a cephalosporin (JP Freiman et al, JAMA, 262:902, August 18, 1989).

Cefixime (Suprax - Lederle), an oral cephalosporin antibiotic, was recently approved for marketing by the US Food and Drug Administration. Claimed to be the first oral third-generation cephalosporin, the new drug is offered for once-a-day treatment of otitis media, pharyngitis, bronchitis and urinary tract infections.

A topical formulation of 0.75% metronidazole gel (MetroGel - Curatek), an antibacterial, antiparasitic agent, was recently approved by the US Food and Drug Administration for treatment of rosacea.

Lyme disease, a multisystem bacterial transmitted by Ixodid ticks, particularly in early summer, continues to be a common problem in the USA and many other countries. Since last year (Medical Letter, 30:65, 1988), some new information has become available, but data on the choice, dosage and duration of antibiotic therapy are still available, but data on the choice, dosage and duration of antibiotic therapy are still limited.

Pneumocystis carinii pneumonia (PCP) is a common cause of death in patients with acquired immune deficiency syndrome (AIDS). PCP is the first serious opportunistic infection in more than 60% of patients with AIDS, and about 80% of AIDS patients develop PCP at least once (AE Glatt et al, N Engl J Med, 318:1439, June 2, 1988). Many studies using drugs to prevent PCP in patients with AIDS have recently been reported.

A penicillin is the drug of choice for treatment of many infections, but allergic reactions to these drugs occur frequently and, rarely, can be fatal. From 5% to 20% of patients have a history of a rash or some other reaction while taking a penicillin, but maculopapular rashes with ampicillin or amoxicillin, especially in children with infectious mononucleosis, are probably not allergic.

Lyme Disease, a multisystem inflammatory disorder transmitted by lxodid ticks and caused by the spirochete Borrelia burgdorferi, is now the most common tick-transmitted illness in the USA. It has been reported in 32 states and on all other continents except Antarctica. Infected ticks have been found not only in wooded areas, but also on well-maintained suburban lawns (RC Falco and D Fish, Am J Epidemiol, 127:826, April 1988). Optimal treatment for this newly discovered disease is still being determined, but some recommendations based on published experience and work in progress can be made.

Cefuroxime axetil (Ceftin - Glaxo), an oral form of the second-generation parenteral cephalosporin cefuroxime (Zinacef), was recently marketed in the USA. Previously available oral cephalosporins are the first-generation drugs cephalexin (Keflex; and others), cephradine (Anspor; and others) and cefadroxil (Duricef; and others), and the second-generation cefaclor (Ceclor); second-generation cephalosporins have more activity against gram-negative bacteria.

Mupirocin (Bactroban - Beecham), a topical antibiotic formerly called pseudomonic acid, was recently approved by the US Food and Drug Administration for treatment of impetigo. It will be sold as a 2% ointment available only by prescription.

After many years of decline, the incidence of tuberculosis has recently increased because the disease occurs in patients with AIDS (Morbid Mortal Weekly Rep, 36:817, Jan 1, 1988). For uncomplicated tuberculosis, the recent trend in tuberculosis treatment has been toward a shorter period of therapy and increased use of pyrazinamide.

Since The Medical Letter last reviewed the choice of antimicrobial drugs, some new drugs have become available, and some new clinical studies of older drugs have been published. The drug of choice for treatment of an infection is usually the most active drug against the pathogenic organism or the least toxic alternative among several effective agents. Sometimes the choice of drugs is modified by the site of infection; one drug may penetrate better than another into bile, urine, or cerebrospinal fluid. The patient's clinical status may also influence the choice as, for example, when a patient has diminished renal or hepatic function, is allergic to penicillin is immunocompromised, or is pregnant. Finally, when other factors are about equal, the relative cost may be a consideration.

Ciprofloxacin hydrochloride (Cipro - Miles), a synthetic antibacterial agent, was recently marketed in the USA for oral treatment of a wide variety of infections. Ciprofloxacin is the second fluoroquinolone to become available in this country; norfloxacin (Noroxin - Medical Letter, 29:25, 1987) is marketed only for treatment of urinary tract infections. Fluoroquinolones are more potent and have a much broader spectrum of activity than older quinolones such as nalidixic acid (NegGram).