The FDA has approved Exblifep (Allecra), a fixed-dose combination of the cephalosporin cefepime and the beta-lactamase inhibitor enmetazobactam, for IV treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis, caused by designated susceptible microorganisms (see Spectrum of Activity). Exblifep is the first product that contains enmetazobactam to be approved in the US.

The FDA has approved a 0.25% ophthalmic solution of the ectoparasiticide lotilaner (Xdemvy – Tarsus) for treatment of Demodex blepharitis. Lotilaner is the first drug to be approved in the US for this indication.

Since 2007, antimicrobial prophylaxis for dental procedures has been recommended to prevent viridans group streptococcal infective endocarditis only for patients at highest risk of an adverse outcome. Limiting use to such patients does not appear to have led to an increased incidence of infective endocarditis or increased mortality due to infective endocarditis.

The FDA has approved Xacduro (Innoviva), a combination of the beta-lactam antibacterial sulbactam and the beta-lactamase inhibitor durlobactam, for IV treatment of adults with hospital-acquired or ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (ABC).

The FDA has approved Vowst (Seres Therapeutics/Nestle HealthScience), an oral capsule containing live fecal microbiota spores, for prevention of additional recurrences of Clostridioides difficile infection (CDI) in adults. Vowst is the first orally administered microbiota-based treatment to be approved for this indication. A rectally-administered live fecal microbiota-based suspension (Rebyota) was approved in 2022 for the same indication. Neither product is approved for acute treatment of CDI.

Most respiratory tract infections are caused by viruses. Bacterial respiratory tract infections are usually treated empirically with antibiotic therapy that targets the most probable causative pathogens. Recommended antibiotic regimens for outpatient treatment of some common respiratory tract infections are listed in Table 1 for adults and Table 2 for children.

The FDA has approved Rebyota (Ferring), a rectally-administered, live fecal microbiota suspension, for prevention of additional recurrences of Clostridioides difficile infection (CDI) following antibiotic treatment for a recurrent episode of CDI in adults. Rebyota is the first microbiome-based treatment to be approved for this indication. It is not approved for initial treatment of CDI. Fecal microbiota transplantation (FMT) has been used in patients with multiple CDI recurrences.

The FDA has approved Twyneo (Galderma), a cream containing the retinoid tretinoin and the oxidizing agent benzoyl peroxide, for once-daily topical treatment of acne in patients ≥9 years old.

The FDA has approved Winlevi (Sun), a 1% cream formulation of the androgen receptor inhibitor clascoterone, for treatment of acne vulgaris in patients ≥12 years old. It is the first topical androgen receptor inhibitor to be approved by the FDA.

Clostridioides (formerly Clostridium) difficile infection (CDI) is the most common infectious cause of healthcare-associated diarrhea in adults. Guidelines on management of CDI have recently been updated.

The FDA has approved Kimyrsa (Melinta), a new IV formulation of the long-acting lipoglycopeptide antibiotic oritavancin, for treatment of adults with acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria. Orbactiv (Melinta), another IV formulation of oritavancin, was approved in 2014 for the same indication. Kimyrsa has a smaller infusion volume (250 mL vs 1 L) and a shorter infusion time (1 hour vs 3 hours) compared to Orbactiv (see Table 1).

Lyme disease in the US is caused by the spirochete Borrelia burgdorferi, which is transmitted to humans by Ixodes scapularis (blacklegged [deer] tick) and I. pacificus (western blacklegged tick). Most cases of Lyme disease occur in late spring and early summer in northeastern and mid-Atlantic states, the upper Midwest, and in northern California. B. mayonii, which is also transmitted by I. scapularis, has been shown to cause a similar illness in the upper Midwest.

Treatment of community-acquired pneumonia (CAP) is usually empiric, with selected antibiotic regimens directed against some of the most common causative pathogens. Recommended empiric regimens are listed in Table 2; recommended antibiotic dosages for treatment of CAP are listed in Tables 3 and 4. Joint guidelines for treatment of CAP by the American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA) were updated in 2019.

The FDA has approved Gimoti (Evoke), a nasal spray formulation of the dopamine-2 (D₂) receptor antagonist metoclopramide, for relief of symptoms in adults with acute and recurrent diabetic gastroparesis. Metoclopramide (Reglan, and generics) has been available for years in conventional and orally-disintegrating tablets and in an injectable formulation. It is the only drug that is FDA-approved for treatment of diabetic gastroparesis.

Acne is common among adolescents and young adults, but its prevalence appears to have increased in people of all ages due to prolonged wearing of masks during the COVID-19 pandemic. Guidelines for treatment of acne were last published in 2016.

The main goals of treatment for chronic obstructive pulmonary disease (COPD) are to relieve symptoms, reduce the frequency and severity of exacerbations, and prevent disease progression. Several guidelines and review articles on COPD treatment have been published in recent years. Treatment of acute exacerbations is not discussed here.

The FDA has approved a fixed-dose combination of omeprazole, amoxicillin, and rifabutin (Talicia – RedHill) for treatment of Helicobacter pylori infection in adults. Talicia is the first rifabutin-based product to be approved for this indication.

The FDA has approved cefiderocol (Fetroja – Shionogi), a new IV cephalosporin antibiotic, for treatment of complicated urinary tract infections (UTI) caused by susceptible gram-negative bacteria in adults who have limited or no alternative treatment options.

The FDA has approved a 4% aerosol foam formulation of minocycline (Amzeeq – Foamix) for topical treatment of inflammatory lesions of non-nodular moderate to severe acne in patients ≥9 years old. It is the first topical tetracycline formulation to be approved for use in patients with acne. Oral minocycline (Minocin, Solodyn, and generics) is

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain and altered bowel habits, often accompanied by bloating.IBS is classified according to the predominant bowel symptom as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), or unclassified (IBS-U). Alterations in the microbiome, stress responses, sensory and motor function of the gut, and host genetic factors may be contributing factors. Since the exact cause of IBS is unknown, the goal of treatment is symptom control.

The FDA has approved omadacycline (Nuzyra – Paratek), a semisynthetic tetracycline derivative, for once-daily IV and oral treatment of community-acquired bacterial pneumonia (CAP) and acute bacterial skin and skin structure infections (ABSSSIs) in adults.

Eravacycline (Xerava – Tetraphase), a new synthetic tetracycline antibiotic, has been approved by the FDA for IV treatment of complicated intra-abdominal infections (cIAIs) in adults. Eravacycline is structurally similar to tigecycline (Tygacil, and generics), a broad-spectrum tetracycline approved by the FDA for IV treatment of complicated skin and skin structure infections, complicated intra-abdominal infections, and community-acquired pneumonia. A higher rate of mortality has been reported with use of tigecycline compared to other antibacterial drugs; it should be used only when no suitable alternative is available.

The FDA has approved a 1% cream formulation of ozenoxacin (Xepi – Cutanea), a nonfluorinated quinolone antibiotic, for treatment of impetigo caused by Staphylococcus aureus or Streptococcus pyogenes in patients ≥2 months old.

Management of both ulcerative colitis (UC) and Crohn's disease (CD) is based on disease severity. Disease location (proctitis, left-sided colitis, or extensive colitis) also plays a role in drug selection. Some drugs for induction and maintenance of remission of inflammatory bowel disease (IBD) are listed in Table 1.

The FDA has approved a fixed-dose combination of meropenem, a carbapenem antibiotic, and vaborbactam, a new beta-lactamase inhibitor (Vabomere – Melinta), for IV treatment of adults with complicated urinary tract infections (UTIs) that are proven or strongly suspected to be caused by Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae spp. complex. Meropenem (Merrem, and generics) has been approved for years for treatment of complicated skin and skin structure infections, intra-abdominal infections, and bacterial meningitis. Resistance to meropenem and other carbapenems, mainly due to production of carbapenemases and other extended-spectrum beta-lactamases (ESBLs), has been increasing worldwide, particularly among Enterobacteriaceae. Vabomere is the first carbapenem/beta-lactamase inhibitor combination to be marketed in the US.

The FDA has approved delafloxacin (Baxdela – Melinta), an anionic fluoroquinolone antibiotic, for oral and parenteral treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is the first fluoroquinolone to be approved for treatment of MRSA.

View the Comparison Table: Some Antibiotics for MRSA Skin and Skin Structure Infections

View the Comparison Table: Some Systemic Fluoroquinolones (online only)

Gastroesophageal reflux disease (GERD) is the most frequent GI condition encountered in the outpatient setting; it affects about 20% of the US population. Heartburn and regurgitation are the classic symptoms of GERD.

Bacterial infections in adults are generally treated empirically, with the antibiotic covering most, but not all, of the potential causative pathogens. For some infections, culture and sensitivity testing can guide treatment, allowing for use of narrower-spectrum antibiotics. The recommended dosages and durations of antibiotic treatment for common respiratory, skin, and urinary tract infections are listed in Tables 1-3. Infectious disease experts now recommend shorter treatment durations for many infections to reduce the development of antimicrobial resistance and minimize adverse effects.

About 50% of the world’s population is infected with Helicobacter pylori. These gastric bacteria can cause chronic inflammation and have been associated with development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Eradication of H. pylori can promote gastric healing, prevent recurrence of duodenal and gastric ulcers, and reduce the incidence of gastric cancer. Guidelines for treatment of H. pylori infection were updated recently.

The text and tables that follow include recommendations for management of sexually transmitted infections (STIs) other than HIV and viral hepatitis. Some of the indications and dosages recommended here have not been approved by the FDA.

The FDA has approved dupilumab (Dupixent – Sanofi/Regeneron), a subcutaneously-injected fully human monoclonal antibody, for treatment of adults with moderate to severe atopic dermatitis (eczema) that has not responded to topical therapies. It can be used with or without topical corticosteroids.

Antimicrobial prophylaxis can decrease the incidence of postoperative surgical site infection after some procedures. Since the last Medical Letter article on this subject, consensus guidelines have been published. Recommendations for prophylaxis in specific surgical procedures are listed in Table 1.

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 promotes development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

This common, chronic inflammatory facial eruption of unknown cause is more prevalent in women than in men. Rosacea is characterized by erythema and telangiectasia, and sometimes by recurrent, progressive crops of acneiform papules and pustules, usually on the central part of the face. Some patients develop granulomas and tissue hypertrophy, which may lead to rhinophyma (a bulbous nose), particularly in men. Blepharitis and conjunctivitis are common. Keratitis and corneal scarring occur rarely.

The FDA has approved ceftolozane/tazobactam (Zerbaxa – Cubist), a combination of a new cephalosporin antibiotic and a beta-lactamase inhibitor, for intravenous treatment of complicated urinary tract and intra-abdominal infections in adults.

The FDA has approved oritavancin (Orbactiv – The Medicines Company), a long-acting lipoglycopeptide antibiotic given as a single intravenous (IV) dose, for treatment of acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria in adults. It is the third lipoglycopeptide antibiotic to be marketed in the US; telavancin (Vibativ) and dalbavancin (Dalvance) were approved earlier.

The FDA has approved two new drugs for treatment of adults with acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria. Dalbavancin (Dalvance – Durata) is a long-acting intravenous (IV) lipoglycopeptide antibiotic similar to telavancin (Vibativ). Tedizolid phosphate (Sivextro – Cubist) is an IV and oral oxazolidinone antibacterial drug similar to linezolid (Zyvox). A third IV antibiotic, oritavancin (Orbactiv), recently approved by the FDA for the same indication, will be reviewed in a future issue.

Aminosalicylates are effective for induction and maintenance of remission in mild to moderate ulcerative colitis. They are not recommended for treatment of Crohn's disease.

FORMULATIONS — Oral mesalamine is rapidly absorbed in the small intestine and most of the drug does not reach the colon. Pentasa releases mesalamine gradually throughout the gastrointestinal tract. Delzicol, Asacol HD, Lialda, and Apriso delay the release of the drug until it reaches the distal ileum and colon. Sulfasalazine (Azulfidine, and generics), balsalazide (Colazal, and others), and olsalazine (Dipentum) are prodrugs; mesalamine is azo-bonded to a second moiety and released in the colon following bacterial cleavage of the bond. Mesalamine is also available as an enema (Rowasa, and generics) and as a rectal suppository (Canasa).

The FDA has approved another solution of the aminoglycoside antibiotic tobramycin (Bethkis – Chiesi/Cornerstone) for oral inhalation via a nebulizer for management of cystic fibrosis (CF) patients with Pseudomonas aeruginosa.

Methicillin-resistant Staphylococcus aureus (MRSA), which was traditionally a nosocomially-acquired organism but now frequently occurs in the absence of healthcare exposure, is the predominant cause of suppurative skin and soft-tissue infections in many parts of the US. Community-associated MRSA usually causes furunculosis, purulent cellulitis, and abscesses, but necrotizing fasciitis, necrotizing pneumonia, and sepsis can also occur.

An outbreak (8 cases to date) of meningococcal disease at Princeton University caused by Neisseria meningitidis serogroup B has led the FDA and CDC to permit importation and investigational use (at Princeton University only) of a meningococcus B vaccine (4CMenB; Bexsero – Novartis) that has not been approved in the US. Bexsero has been approved for use in the European Union and in Australia.

THE VACCINE — Until recently, no serogroup B vaccine was widely available because the polysaccharide capsule of the B serogroup, unlike those of the other main meningococcal serogroups (A, C, Y, and W-135), is only weakly immunogenic. The 4CMenB vaccine contains 3 protein antigens identified in the N. meningitidis serogroup B genome and membrane components from a New Zealand outbreak strain. The vaccine has been tested in more than 8000 adults and children, has proved to be immunogenic, and appears to be safe.1 Its efficacy has not been established clinically, but laboratory testing, according to the CDC, has found that the vaccine should be protective against the strain causing the Princeton University outbreak. Bactericidal antibody levels develop about 2 weeks after one dose of the vaccine; a second dose is needed 1-6 months after the first to maintain protection.

CHEMOPROPHYLAXIS — Close contacts of patients with invasive meningococcal disease (e.g., same household, roommates, boyfriend or girlfriend) should receive antimicrobial chemoprophylaxis. Antimicrobial drugs can prevent secondary cases and eradicate the organism from the nasopharynx of healthy carriers. The susceptibility of serogroup B meningococci to antimicrobial agents is the same as that of other meningococcal serogroups. Regimens recommended by the CDC’s Advisory Committee on Immunization Practices are: oral rifampin 600 mg (10 mg/kg for children) q12h for 2 days; oral ciprofloxacin 500 mg once (not recommended for children); or a single IM injection of ceftriaxone 250 mg (125 mg for children).2

CONCLUSION — The new vaccine against serogroup B meningococcal disease, which is investigational in the US, appears to be immunogenic and safe. For immediate protection after close contact with an infected patient, antimicrobial prophylaxis is recommended.

1. NJ Carter. Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero®): a review of its use in primary and booster vaccination. BioDrugs 2013; 27:263.

2. AC Cohn et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013; 62(RR-2):1.

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The FDA is requiring new warnings about peripheral neuropathy in the labeling of all oral and injectable fluoroquinolones. The potential for this class of antibiotics to cause peripheral neuropathy was first identified more than 10 years ago and a warning was added to their labels in 2004. The new warnings are based on a recent review of the FDA’s Adverse Event Reporting System (AERS) database.1

The onset of peripheral neuropathy can occur rapidly, often within a few days of starting a fluoroquinolone, and in some patients the disorder may be permanent. Symptoms include pain, tingling, burning, numbness, weakness, and change in sensation to touch, pain, and temperature in the arms and/or legs. If peripheral neuropathy develops in a patient taking a fluoroquinolone, the drug should be stopped and an antibacterial from a different class should be used instead.2

1. FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. Available at http://www.fda.gov. Accessed November 1, 2013.

2. Drugs for bacterial infections. Treat Guidel Med Lett 2013; 11:65.

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The text that follows reviews some common bacterial infections and their empiric treatment pending the results of culture and susceptibility testing. The recommendations made here are based on the results of susceptibility studies, clinical trials, and the opinions of Medical Letter reviewers. Tables 1 and 2 list the usual dosages of antibacterial drugs.

Inhaled antibiotics, which can achieve high concentrations in the lung with minimal systemic side effects, are probably the most effective therapy available for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis. An orally inhaled dry powder formulation of the aminoglycoside antibiotic tobramycin (Tobi Podhaler – Novartis) has been approved by the FDA for management of P. aeruginosa pulmonary infection in cystic fibrosis patients ≥6 years old. The new formulation is administered via a hand-held pocket-sized inhaler. Tobramycin is also available as an inhalation solution (Tobi) for administration via a nebulizer. An inhalation solution of aztreonam (Cayston), administered via a nebulizer, is also approved for this indication.

The use of drugs to prevent and control symptoms of allergic disorders can be optimized when patients avoid exposure to specific allergens and/or environmental conditions that trigger or worsen their symptoms.

The FDA has announced that it is requiring changes in the labeling of the macrolide antibiotic azithromycin (Zithromax, Zmax) to warn about the risk of QT prolongation and cardiac arrhythmias.1 The new warnings are based on a retrospective study in The New England Journal of Medicine (reviewed previously in The Medical Letter2), which found that among patients who received 347,795 prescriptions for azithromycin, there were 29 cardiovascular deaths, a significantly higher rate than the 42 that occurred among patients who received 1,348,672 prescriptions for amoxicillin (which does not prolong the QT interval) or the 41 that occurred among 1,391,180 patients who took no antibiotics. The risk with azithromycin was much higher in patients with cardiovascular risk factors.3

Other macrolides and fluoroquinolones can also prolong the QT interval. In the retrospective study, the risk of cardiovascular death with levofloxacin was not significantly different from the risk with azithromycin. As with any retrospective study, the possibility that baseline differences between patients taking azithromycin and those taking other or no antimicrobials could have been responsible for the difference in cardiovascular outcomes cannot be entirely ruled out.

1. FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. Available at www.fda.gov/drugs/drugsafety/ucm341822.htm. Accessed March 14, 2013.

2. In brief: safety of azithromycin. Med Lett Drugs Ther 2012; 54:45.

3. WA Ray et al. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012; 366:1881.

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Antimicrobial prophylaxis can decrease the incidence of postoperative infection, particularly surgical site infection, after some procedures. Recommendations for such prophylaxis are listed in the table that begins on page 74. Antimicrobial prophylaxis for dental procedures to prevent endocarditis was recently discussed in The Medical Letter.

A reader suggested that our July 23 article on Drugs for Urinary Tract Infection (Med Lett Drugs Ther 2012; 54:57)¹ should have included information on the cost of the drugs we recommended for treatment of acute uncomplicated cystitis.

Trimethoprim/sulfamethoxazole DS — Generic formulations are available at large discount pharmacies for $4 for 20 tablets. Trimethoprim/sulfamethoxazole DS is generally found on tier 1 (lowest co-pay) of insurance company formularies.

Nitrofurantoin monohydrate/macrocrystals — The wholesale acquisition cost of the generic formulation is about $2.50 per tablet (PricePointRx™).² The drug is on tier 1 of some insurance company formularies, but on tier 2 or 3 of others.

Fosfomycin — Available only as Monurol, a single dose of fosfomycin is effective in most cases of acute uncomplicated cystitis, but the manufacturer charges a wholesale acquisition cost of more than $40 for that dose (PricePointRx™).² Most insurance companies place Monurol on tier 3 of their formularies, or do not include it on their formularies at all.

Not recommended: Ciprofloxacin – Fluoroquinolones should not be used empirically to treat acute uncomplicated cystitis. The fact that ciprofloxacin is available at large discount pharmacies for $4 for 20 500-mg tablets and is on tier 1 on most insurance company formularies may be part of the reason for its continued overuse.

1. Drugs for urinary tract infection. Med Lett Drugs Ther 2012; 54:57.

2. PricePointRx™. Reprinted with permission by FDB. All rights reserved. ©2012. http://www.firstdatabank.com/support/drug-pricing-policy.aspx. Accessed July 31, 2012. Actual retail prices may be higher.

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The most recent guidelines from the Infectious Diseases Society of America (IDSA) and its European counterpart on the choice of antimicrobials for treatment of uncomplicated urinary tract infections (UTIs) in non-pregnant women focus on the unnecessary use of fluoroquinolones to treat uropathogens that are increasingly becoming resistant to them. Resistance of Escherichia coli to ciprofloxacin in the US has increased from 3% in 2000 to 17.1% in 2010.

Recently published results of a large, carefully conducted retrospective study indicated that use of the antibiotic azithromycin (Zithromax, and others) may increase the risk of cardiovascular death, especially in patients with a high baseline risk of cardiovascular disease.1 One possible mechanism is prolongation of the QT interval, which is known to occur rarely with azithromycin and more frequently with the other macrolide antibiotics erythromycin (Erythrocin, and others) and clarithromycin (Biaxin, and others).

Among the patients who received 347,795 prescriptions for azithromycin, there were 29 cardiovascular deaths, a significantly higher rate than the 42 that occurred among the patients who received 1,348,672 prescriptions for amoxicillin (which does not prolong the QT interval) or the 41 that occurred among the 1,391,180 patients who took no antibiotics. Among patients with the highest baseline risk of cardiovascular disease, treatment with azithromycin, compared to amoxicillin, would have resulted in 245 additional cardiovascular deaths per million courses of the antibiotic.

As with any retrospective study, there could have been some undetected differences between the patients who received one drug or the other, but use of an appropriate non-macrolide alternative2 instead of azithromycin might be reasonable in patients with cardiovascular disease or in those who are taking other drugs that can prolong the QT interval (www.azcert.org).

1. WA Ray et al. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012; 366:1881.

2. Drugs for bacterial infections. Treat Guidel Med Lett 2010; 8:43.

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Patients planning to travel to other countries often ask for information about appropriate vaccines and prevention of diarrhea and malaria. More detailed advice for travelers is available from the Centers for Disease Control and Prevention (CDC) at www.cdc.gov/travel. Guidelines are also available from the Infectious Diseases Society of America (IDSA).

The FDA has required the manufacturer of the secondgeneration antipsychotic quetiapine (Seroquel) to add a warning to the labeling saying that use of the drug should be avoided in combination with other drugs that prolong the electrocardiographic QTc interval (Table 1). The warning is based only on postmarketing reports of QT-interval prolongation in patients who overdosed on the drug, had concomitant illness, or were taking other drugs known to cause electrolyte imbalances or increase the QT interval. QT prolongation can lead to torsades de pointes, a potentially fatal cardiac arrhythmia.

Peptic ulcer disease (PUD) is usually caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or by infection with Helicobacter pylori. Gastroesophageal reflux disease (GERD) can be caused by transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, hiatal hernia, delayed gastric emptying or hormonal changes due to pregnancy. Acid suppressive therapy is the cornerstone of management for both PUD and GERD.

The FDA has announced changes in the labeling of simvastatin to reduce the risk of myopathy. These changes include limiting the use of the 80-mg maximum dose to patients who have been taking it for 12 months or more without evidence of myopathy and new recommendations for use of simvastatin with other drugs. Simvastatin is available alone (Zocor, and others) and in combination with ezetimibe (Vytorin) and with niacin (Simcor).

A Medical Letter reader has asked us to review the safety of the fluoroquinolone antibiotic levofloxacin (Levaquin – Ortho-McNeil-Janssen), which has just been approved for generic use by the FDA and has been at the center of some recent lawsuits regarding the adequacy of its safety warnings.

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-associated diarrhea in adults. The incidence and severity of CDI have increased in recent years with the emergence of an epidemic virulent strain (NAP1/BI/027). Common risk factors include admission to a healthcare facility, increasing age and severity of underlying illness, gastric acid suppression and exposure to antimicrobials, particularly clindamycin, ampicillin, cephalosporins or fluoroquinolones. Patients who develop CDI while receiving a precipitating antibiotic should have the antibiotic discontinued, if possible, or switched to another appropriate antimicrobial with a lower risk of CDI.

The FDA has approved ceftaroline fosamil (Teflaro – Forest), an intravenous (IV) cephalosporin, for treatment of acute bacterial skin and skin structure infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA), and for treatment of community-acquired bacterial pneumonia in adults. It is the first beta-lactam antibiotic approved for treatment of MRSA.

The text below reviews some common bacterial infections and their treatment. The recommendations made here are based on the results of susceptibility studies, clinical trials and the opinions of Medical Letter consultants.

The FDA has approved the fluoroquinolone besifloxacin 0.6% ophthalmic suspension (Besivance - Bausch & Lomb) for treatment of bacterial conjunctivitis caused by susceptible bacteria. According to the manufacturer, this product was developed specifically for ophthalmic use in a specialized vehicle designed to prolong contact time on the ocular surface. Besifloxacin is not available for systemic use.

The FDA has added a boxed warning to fluoroquinolone package inserts about tendon injuries that may occur as a result of their use. Tendinitis or tendon rupture may occur rarely with systemic use of any fluoroquinolone, either while the drug is being taken or for up to several months afterwards.

Fluoroquinolone-related tendon injury is rare; estimates for its incidence in the general population range from 0.14% to 0.4%. The risk is higher for patients >60 years old and for those taking corticosteroids. For patients with organ transplants, the incidence may be as high as 15%.1 A case-control study in Italy involving 22,194 cases of non-traumatic tendinitis and 104,906 controls found that fluoroquinolone use was significantly associated with tendon disorders in general (OR 1.7; 95% CI 1.4-2.0), tendon rupture (OR 1.3; 95% CI 1.0-1.8), and Achilles tendon rupture (OR 4.1; 95% CI 1.8-9.6). Achilles tendon rupture occurred with fluoroquinolone treatment in one of every 5989 patients in general and in one of every 1638 patients >60 years old.2

Widespread use of fluoroquinolones, particularly for treatment of respiratory infections, has produced substantial bacterial resistance to this class of drugs and has been associated with an increase in the incidence and severity of Clostridium difficile disease.3 Even when bacterial pneumonia is considered a likely possibility, other drugs are generally preferred, at least in non-elderly, otherwise healthy patients.4

1. F Muzi et al. Fluoroquinolones-induced tendinitis and tendon rupture in kidney transplant recipients: 2 cases and a review of the literature.Transplant Proc 2007; 39:1673.
2. G Corrao et al. Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study. Drug Saf 2006; 29:889.
3. Treatment of Clostridium difficile-associated disease (CDAD). Med Lett Drugs Ther 2006; 48:89.
4. Drugs for community-acquired bacterial pneumonia. Med Lett Drugs Ther 2007; 49:62.

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The most common cause of travelers' diarrhea, usually a self-limited illness without fever lasting several days, is infection with noninvasive enterotoxigenic (ETEC) or enteroaggregative (EAEC) strains of Escherichia coli. Campylobacter, Shigella, Salmonella, Aeromonas, viruses and parasites are less common.

Retapamulin (re-tap'-a-mue'-lin; Altabax - Glaxo SmithKline) is a topical antibiotic recently approved by the FDA for treatment of bullous and non-bullous impetigo due to Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus. It is available as a 1% ointment by prescription only.

The FDA has approved azithromycin 1% ophthalmic solution (AzaSite - Inspire) for treatment of bacterial conjunctivitis in patients > 1 year old. It is formulated, according to the manufacturer, in a controlled-release delivery system that keeps the drug in the eye for several hours.

Doripenem (Doribax - Ortho-McNeil Janssen), an intravenous (IV) carbapenem antibiotic with a spectrum of activity similar to that of imipenem and meropenem, has been approved by the FDA for treatment of complicated intra-abdominal and urinary tract infections. Use of doripenem for treatment of nosocomial pneumonia, including ventilator-associated pneumonia, is still under FDA review.

Most patients with community-acquired pneumonia (CAP) are treated empirically. New guidelines published jointly by the Infectious Diseases Society of America and the American Thoracic Society have recently become available.

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.

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.

Many physicians believe that antimicrobial prophylaxis before procedures that may cause transient bacteremia can prevent endocarditis and prosthetic joint infection in patients at increased risk for these disorders. The effectiveness of this common practice has never been established by controlled trials in humans.

The pathogenesis of acne is multifactorial: follicular hyperkeratinization, Propionibacterium acnes bacteria, sebum production, androgens and inflammation have all been implicated. P. acnes, a gram-positive microaerophilic bacterium, plays an important role in the development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

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.

Since The Medical Letter last reviewed the choice of drugs for treatment of bacterial infections (vol. 38, page 25, 1996), and few new information and some new information about older drugs drugs have become available. Empirical treatment of some infections is discussed. A table listing the drugs of choice and alternatives for each pathogen begins on page 37. These recommendations are based on results of susceptibility studies, clinical trials and the opinions of Medical Letter consultants. (Superseded by issue 1064, 10/22/99)

Meropenem (Merrem - Zeneca), a carbapenem similar to imipenem-cilastatin (Primaxin), has been approved by the US Food and Drug Administration for intravenous (IV) treatment of complicated intra-abdominal infections in adults and children and bacterial meningitis in children more than three months old. Imipenem (Medical Letter, 28:29, 1986) has been useful for treatment of serious infections in which broad coverage of nosocomial organisms, including anaerobes, is needed. Other drugs for these indications were reviewed in the Medical Letter article on 'The Choice of Antibacterial Drugs' (volume 38, page 25, March 29, 1996).

Cefepime hydrochloride (Maxipime - Bristol-Myers Squibb), a new 'fourth-generation' cephalosporin, has been approved by the US Food and Drug Administration (FDA) for parenteral treatment of urinary tract infections and skin and skin-structure infections due to susceptible pathogens, and for moderate to severe pneunmonia caused by Streptococcus pneumoniae (pneumococci), Pseudomonas aeruginosa, Enterobacter or Klebsiella pneumoniae.

New drugs for treatment of bacterial infections and new information about older drugs continue to become available. Empirical treatment of some infections is discussed below. A table listing the drugs of choice and alternatives for each pathogen begins on page 73. 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.

Dirithromycin (Dynabac - manufactured by Lilly, distributed by Bock), an oral macrolide antibiotic chemically similar to erythromycin, clarithromycin (Biaxin) and azithromycin (Zithromax), has been approved for marketing by the US Food and Drug Administration (FDA).

A drug that combines the neutral sulfate salts of dextroamphetamine and racemic amphetamine with the dextro isomer of amphetamine saccharate and d,l amphetamine aspartate (Adderall - Richwood Pharmaceutical) has recently been promoted for treatment of children with Attention-Deficit/Hyperactivity Disorder (ADHD). This same mixture of amphetamine salts was previously marketed as Obetrol for treatment of obesity.

Since The Medical Letter last reviewed the choice of antibacterial drugs (vol.34, page 49, 1992), a few new drugs have become available, and some clinical trials of older drugs have been published.

Gabapentin (Neurontin - Parke-Davis), a cyclohexane acetic acid derivative, has been approved by the US Food and Drug Administration for use in addition to other antiepileptic drugs in patients with partial (focal) seizures with or without secondary generalization. Since this diagnostic category includes the largest number of patients with intractable epilepsy, new drugs with antiepileptic activity are generally tried first for this indication.

Piperacillin/tazobactam (Zosyn - Lederle), an antibiotic combination product, has been approved by the US Food and Drug Administration for intravenous treatment of intra-abdominal, pelvic, skin, and skin-structure infections and for community-acquired pneumonia of moderate severity.