SAN FRANCISCO, Sept. 14, 2009 – Results from Merck & Co., Inc.’s 2008 Study for Monitoring Antimicrobial Resistance Trends (SMART), presented today at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), show the in vitro susceptibilities of Escherichia coli (E. coli) bacteria, isolated from intra-abdominal infections (IAIs), when tested against commonly used antibiotics. The data also showed the latest regional rates of extended-spectrum ß-lactamases positive E.coli strains (ESBL + E. coli). ESBLs are enzymes produced by bacteria such as E. coli and are one cause of antibiotic resistance. The data demonstrated that globally, nearly one-fifth (19.4 percent) of the IAI E. coli isolates analyzed in this study were ESBL+ strains.
“Resistant E. coli bacteria are on the rise in different regions of the world,” said Maria Virginia Villegas, M.D., MSc, executive director, CIDEIM, International Center for Training and Medical Research, Cali, Colombia. “The difference between the in vitro susceptibility of ESBL+ and ESBL negative (-) E. coli against the antibiotics tested in SMART indicate that it is important to have an understanding of local ESBL prevalence data.”
Bacterial infections, such as IAIs, infectious diarrhea and urinary tract infections can be caused by E. coli. Antibiotic medications are used to treat E. coli infections; however, infections caused by resistant strains of E.coli bacteria may be less susceptible to some antibiotics.
The SMART findings presented include pooled data collected in 2008 from 116 clinical sites in 44 countries in six regions of the world (North America, Africa, Middle East, Europe, Asia/Pacific, Latin America). A total of 3,093 isolates of E. coli were collected from IAI patient specimens and analyzed for ESBL status confirmation as well as susceptibility to 12 commonly-used antibiotics. Testing was performed in accordance with Clinical Laboratory Standards Institute (CLSI) guidelines.
Results showed the global rate of ESBL+ E. coli from IAIs was 19.4 percent. Regionally, Latin America had the highest rate and North America had the lowest rate, at 30.6 percent and 2.7 percent, respectively. SMART 2008 results showed the in vitro susceptibility of ESBL+ and ESBL- E. coli isolated from IAIs. These pathogens were collected from hospitals around the world and analyzed by a central laboratory, which confirmed identifications and performed and interpreted susceptibility testing and ESBL confirmation.
About SMART
To meet the challenges with monitoring resistant E. coli and other pathogens, Merck launched SMART in 2002. Since its inception, the SMART program has grown to nearly 150 sites in 42 countries worldwide. Monitoring the global susceptibility of IAI isolates from SMART provides the medical community with an important resource in understanding E. coli resistance.
Hospitals participating in SMART throughout Europe, Latin America, the USA, Canada and the Asia/Pacific and Middle East/Africa regions collect up to 100 consecutive unique clinical isolates, characterized as being collected within 48 hours of hospital admission (community-acquired) or more than 48 hours after admission (hospital-acquired). Duplicate samples are excluded.
About INVANZ® (ertapenem sodium) IV/IM
INVANZ is indicated for the treatment of patients with the following moderate to severe infections caused by susceptible isolates of the designated microorganisms:
• Complicated intra-abdominal infections due to E. coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis (B fragilis), Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.
• Complicated urinary tract infections, including pyelonephritis, due to E. coli, including cases with concurrent bacteremia, or K pneumoniae.
Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to INVANZ. Therapy with INVANZ may be initiated empirically before results of these tests are known; once results become available, antimicrobial therapy should be adjusted accordingly.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of INVANZ and other antibacterial drugs, INVANZ should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Selected important safety information about INVANZ
INVANZ is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams.
Due to the use of lidocaine HCl as a diluent, INVANZ administered intramuscularly is contraindicated in patients with a known hypersensitivity to local anesthetics of the amide type.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation.
Seizures and other central nervous system (CNS) adverse experiences have been reported during treatment with INVANZ.
As with other antibiotics, prolonged use of INVANZ may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient’s condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Prescribing INVANZ in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patients and increases the risk of the development of drug-resistant bacteria.
During clinical trials, the most common drug-related adverse experiences in adult patients treated with INVANZ, including those who were switched to therapy with an oral antimicrobial, were diarrhea (5.5 percent), infused vein complication (3.7 percent), nausea (3.1 percent), headache (2.2 percent), vaginitis in females (2.1 percent), phlebitis/thrombophlebitis (1.3 percent), and vomiting (1.1 percent).
INVANZ® is a registered trademark of Merck & Co., Inc., Whitehouse Station , N.J., USA
About PRIMAXIN® I.V. (imipenem and cilastatin)
In intra-abdominal infections, PRIMAXIN I.V. is indicated for the treatment of serious infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Citrobacter species, Enterobacter species, E. coli, Klebsiella species, Morganella morganii*, Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species*, Bacteroides species including B. fragilis, and Fusobacterium species
In Urinary Tract Infections (complicated and uncomplicated) PRIMAXIN I.V. is indicated for the treatment of serious infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains) *, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii*, Proteus vulgaris*, Providenica rettgeri*, and Pseudomonas aeuriginosa
*Efficacy for this organism in this organ system was studied in fewer than ten infections.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of PRIMAXIN I.V. and other antibacterial drugs, PRIMAXIN I.V. should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
PRIMAXIN® is a registered trademark of Merck & Co., Inc., Whitehouse Station , N.J., USA
Selected important safety information about PRIMAXIN I.V.
PRIMAXIN I.V. is contraindicated in patients who have shown hypersensitivity to any component of this product. Before initiating therapy with PRIMAXIN I.V., careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens. If an allergic reaction to PRIMAXIN I.V. occurs, discontinue the drug. Seizures and other CNS adverse events have been reported during treatment with PRIMAXIN I.V.
Central nervous system (CNS) adverse experiences such as confusional states, myoclonic activity, and seizures have been reported during treatment with PRIMAXIN I.V., especially when recommended dosages were exceeded. These experiences have occurred most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) and/or compromised renal function. However, there have been reports of CNS adverse experiences in patients who had no recognized or documented underlying CNS disorder or compromised renal function.
Prescribing PRIMAXIN I.V. in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
The most frequently reported systemic adverse clinical reactions that were reported as possibly, probably, or definitely related to PRIMAXIN I.V. were nausea (2.0%), diarrhea (1.8%), vomiting (1.5 percent), rash (0.9 percent), fever (0.5 percent), hypotension (0.4 percent), seizures (0.4 percent), dizziness (0.3 percent), pruritus (0.3 percent), urticaria (0.2 percent), and somnolence (0.2 percent).
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluents containing benzyl alcohol should not be used when PRIMAXIN I.V. is constituted for administration to pediatric patients in this age range.
Additional selected safety information about INVANZ and PRIMAXIN I.V.
Carbapenems, including ertapenem and imipenem, may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop below the therapeutic range or a seizure occurs.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ertapenem and imipenem, and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use. CDAD has been reported to occur over two months after administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C difficile may need to be discontinued.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Forward-looking statement
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck’s business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck’s Form 10-K for the year ended Dec. 31, 2008, and in any risk factors or cautionary statements contained in the Company’s periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
