The medical letter on drugs and therapeutics may 23 2016

Antimicrobial Prophylaxis for Surgery 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... QuilliChew ER - Extended-Release Chewable Methylphenidate Tablets The FDA has approved a once-daily, extended-release chewable tablet formulation of methylphenidate (QuilliChew ER – Pfizer) for treatment of attention-deficit/hyperactivity disorder... Ciprofloxacin (Otiprio) for Tympanostomy Tube Insertion The FDA has approved ciprofloxacin 6% otic suspension (Otiprio – Otonomy) for single-dose prophylaxis in children with bilateral otitis media with effusion who are undergoing... Three New Drugs for Multiple Myeloma (online only) The FDA recently approved ixazomib (Ninlaro – Takeda), daratumumab (Darzalex – Janssen Biotech), and elotuzumab (Empliciti – BMS) for treatment of relapsed and/or...

The Medical Letter ® on Drugs and Therapeutics Volume 58 ISSUE ISSUE No 1433 1495 Volume 56 May 23, 2016 IN THIS ISSUE Antimicrobial Prophylaxis for Surgery p 63 QuilliChew ER — Extended-Release Chewable Methylphenidate Tablets p 68 Ciprofloxacin (Otiprio) for Tympanostomy Tube Insertion p 69 Three New Drugs for Multiple Myeloma online only Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with U.S and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® on Drugs and Therapeutics Volume 58 ISSUE ISSUE No 1433 1495 Volume 56 ▶ May 23, 2016 ALSO IN THIS ISSUE QuilliChew ER — Extended-Release Chewable Methylphenidate Tablets p 68 Ciprofloxacin (Otiprio) for Tympanostomy Tube Insertion p 69 Three New Drugs for Multiple Myeloma online only Antimicrobial Prophylaxis for Surgery 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.1 Recommendations for prophylaxis in specific surgical procedures are listed in the table that begins on page 64 CHOICE OF AGENT — Antimicrobial prophylaxis for surgery should be directed against the most likely infecting organisms, but it does not need to eradicate every potential pathogen to be effective Cefazolin (Ancef, and others), a first-generation cephalosporin active against many staphylococci and streptococci, can be used for most procedures The second-generation cephalosporins cefoxitin (Mefoxin, and others) and cefotetan (Cefotan, and others) are recommended for procedures that involve exposure to bowel flora, including Escherichia coli and Bacteroides fragilis, but anaerobic resistance to these drugs has increased.2 Ampicillin/sulbactam (Unasyn, and generics), the broad-spectrum carbapenem ertapenem (Invanz), or cefazolin plus metronidazole (Flagyl, and others) may be considered, depending on local susceptibility patterns.3 Most experts not recommend routine use of broadspectrum antibiotics such as ertapenem or extendedspectrum cephalosporins such as cefotaxime (Claforan, and generics), ceftriaxone (Rocephin, and generics), ceftazidime (Fortaz, and others), cefepime (Maxipime, and generics), or ceftaroline (Teflaro) for surgical prophylaxis because they are expensive, some are less active against staphylococci than first- or second-generation cephalosporins, and their spectrum of activity often includes organisms rarely encountered in elective surgery.4 In patients who are colonized with methicillinresistant Staphylococcus aureus (MRSA) or in institutions where surgical site infections are frequently due to methicillin-resistant staphylococci, vancomycin (Vancocin, and others) could be considered for prophylaxis5; it should be given in addition to the routine prophylactic regimen recommended for the procedure Vancomycin is less effective than cefazolin for prevention of infections due to methicillin-susceptible Staphylococcus aureus (MSSA), it has a long infusion time, and regular use possibly could lead to emergence of vancomycin-resistant organisms Preoperative Screening and Decolonization – Preoperative identification of patients who are nasal carriers of MRSA or MSSA and decolonization using intranasal mupirocin (Bactroban Nasal, and others) and chlorhexidine (Peridex, and others) have been shown to decrease surgical site infections following some procedures (primarily cardiac and orthopedic), but resistance to mupirocin could emerge if it is used routinely.6-8 TIMING AND DURATION — Administration of the prophylactic antibiotic should begin within 60 minutes before the initial surgical incision to ensure adequate serum and tissue levels If vancomycin or a fluoroquinolone is used, the infusion should be started within 60-120 minutes before the initial incision because of the prolonged infusion times required for these drugs A single prophylactic dose of an antimicrobial is usually sufficient for most procedures; continuation of prophylaxis for >24 hours after the procedure is not recommended There are no data to support continuation of prophylaxis after wound closure, even if all indwelling drains and intravascular catheters have not yet been removed 63 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter ® Vol 58 (1495) May 23, 2016 Table Antimicrobial Prophylaxis for Surgery Type of Surgical Procedure Recommended Antimicrobials Common Pathogens Usual Adult Dosage1 Cardiac Coronary artery bypass grafting, valve repairs, device implantation Staphylococcus aureus, Staphylococcus epidermidis cefazolin2,3 OR cefuroxime2,3 Gastrointestinal Esophageal, gastroduodenal Entry into the GI lumen or patients at high risk for infection6 Enteric gram-negative bacilli, gram-positive cocci cefazolin3,7 g IV4 Biliary tract Open or high-risk laparoscopic8 Enteric gram-negative bacilli, enterococci, clostridia cefazolin3,7,9 g IV4 Colorectal10 Enteric gram-negative bacilli, anaerobes, enterococci cefazolin + metronidazole3,7 cefoxitin or cefotetan3,7 ampicillin/sulbactam3,7,11 ceftriaxone + metronidazole3,7,12 ertapenem3,7,13 g IV4 0.5 g IV g IV g IV g IV 0.5 g IV g IV OR OR OR OR Appendectomy, non-perforated Enteric gram-negative bacilli, anaerobes, enterococci Hernia Gram-positive cocci cefoxitin or cefotetan3,7 OR cefazolin + metronidazole3,7 cefazolin2,3 g IV4,5 1.5 g IV5 g IV g IV4 0.5 g IV g IV4 Genitourinary Cystoscopy alone Enteric gram-negative bacilli, enterococci High-risk14 only: ciprofloxacin11 OR trimethoprim/ sulfamethoxazole11 Cystoscopy with manipulation or upper tract instrumentation15 Enteric gram-negative bacilli, enterococci ciprofloxacin11 OR trimethoprim/ sulfamethoxazole11 Open or laparoscopic surgery16 Enteric gram-negative bacilli, enterococci cefazolin3,7 500 mg PO or 400 mg IV 160/800 mg (1 DS tab) PO 500 mg PO or 400 mg IV 160/800 mg (1 DS tab) PO g IV4 Parenteral prophylactic antimicrobials can be given as a single IV dose begun within 60 minutes before the initial incision For procedures that exceed halflives of the drug or those with major blood loss, or in patients with extensive burns, additional intraoperative doses should be given at intervals of about times the half-life of the drug (ampicillin/sulbactam q2 hours, cefazolin q4 hours, cefuroxime q4 hours, cefoxitin q2 hours, clindamycin q6 hours, vancomycin q12 hours) for the duration of the procedure in patients with normal renal function If vancomycin or a fluoroquinolone is used, the infusion should be started within 60-120 minutes before the initial incision to have adequate tissue levels at the time of incision and to minimize the possibility of an infusion reaction close to the time of induction of anesthesia Vancomycin (15 mg/kg IV) or clindamycin (900 mg IV) is a reasonable alternative for patients who are allergic to beta-lactams They only provide coverage against gram-positive organisms; for procedures in which enteric gram-negative bacilli are common pathogens, many experts would add an aminoglycoside (gentamicin, tobramycin or amikacin), aztreonam, or a fluoroquinolone A dose of vancomycin (15 mg/kg) can be given in addition to the recommended antimicrobial(s) in patients colonized with MRSA or in hospitals in which methicillin-resistant S aureus and S epidermidis are a frequent cause of postoperative wound infection Vancomycin is less effective than cefazolin in preventing surgical site infections due to methicillin-susceptible Staphylococcus aureus (MSSA) Vancomycin has activity only against gram-positive bacteria; for procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside (gentamicin, tobramycin or amikacin), aztreonam, or a fluoroquinolone Rapid IV administration of vancomycin may cause hypotension, which could be especially dangerous during induction of anesthesia Even when the drug is given over 60 minutes, hypotension may occur; treatment with diphenhydramine (Benadryl, and others) and further slowing of the infusion rate may be helpful An infusion rate of 10-15 mg/minute (≥1 h/1000 mg) has been recommended (T Crawford et al Clin Infect Dis 2012; 54:1474) Dose for patients who weigh 70 years, acute cholecystitis, non-functioning gallbladder, obstructive jaundice, common bile duct stones, duration >120 minutes, diabetes, pregnancy, or immunosuppression Cefotetan, cefoxitin, and ampicillin/sulbactam are reasonable alternatives 10 In addition to mechanical bowel preparation, g of neomycin plus g of erythromycin at PM, PM and 11 PM or g of neomycin plus g of metronidazole at PM and 11 PM the day before an AM operation CARDIAC SURGERY — A preoperative dose of an antibiotic can decrease the incidence of infection after cardiac surgery; appropriate intraoperative redosing should be continued for the duration of the procedure In a study in patients undergoing coronary artery bypass grafting on cardiopulmonary bypass, intraoperative continuous-infusion cefazolin was superior to intermittent dosing every hours.9 64 Antimicrobial prophylaxis is recommended before placement of electrophysiologic devices, ventricular assist devices, ventriculoatrial shunts, and arterial patches to prevent device-related infections Administration of an antimicrobial prior to implantation of permanent pacemakers and cardioverter-defibrillators has been shown to significantly reduce the incidence of wound infection, inflammation, and skin erosion.10 The Medical Letter Vol 58 (1495) ® May 23, 2016 Table Antimicrobial Prophylaxis for Surgery (continued) Type of Surgical Procedure Recommended Antimicrobials Common Pathogens Usual Adult Dosage1 Gynecologic and Obstetric Vaginal, abdominal, or laparoscopic hysterectomy Enteric gram-negative bacilli, anaerobes, Gp B strep, enterococci cefazolin3,7 OR cefoxitin or cefotetan3,7 OR ampicillin/sulbactam3,7,11 g IV4 g IV g IV Cesarean section same as for hysterectomy cefazolin3,7 g IV4 Abortion, surgical same as for hysterectomy doxycycline 300 mg PO17 Head and Neck Surgery Incisions through oral or pharyngeal mucosa Anaerobes, enteric gramnegative bacilli, S aureus cefazolin + metronidazole3,18 OR ampicillin/sulbactam3,11,18 g IV4 0.5 g IV4 g IV Neurosurgery Craniotomy, spinal and CSF-shunting S aureus, S epidermidis, procedures, intrathecal pump Propionibacterium acnes placement cefazolin2,3 g IV4 S epidermidis, S aureus, streptococci, enterococci, P acnes, Corynebacterium spp., enteric gram-negative bacilli, Pseudomonas spp neomycin-gramicidinpolymyxin B, gatifloxacin, or moxifloxacin ± cefazolin drop q5-15 x doses S aureus, S epidermidis, P acnes (shoulder) cefazolin2,3,20 g IV4 Ophthalmic19 100 mg subconjunctivally at the end of the procedure Orthopedic Spinal, hip fracture, internal fixation, total joint replacement Thoracic (Non-Cardiac) Lobectomy, pneumonectomy, lung resection, thoracotomy S aureus, S epidermidis, streptococci, enteric gramnegative bacilli cefazolin2.3 OR ampicillin/sulbactam2,3,11 g IV4 g IV Vascular Arterial involving a prosthesis, the abdominal aorta, or a groin incision S aureus, S epidermidis, enteric gram-negative bacilli cefazolin2,3 g IV4 Lower extremity amputation for ischemia S aureus, S epidermidis, enteric gram-negative bacilli, clostridia cefazolin2,3 g IV4 11 12 13 14 15 16 17 18 19 20 Due to increasing resistance of Escherchia coli, local sensitivity profiles should be reviewed prior to use Where there is increasing resistance of gram-negative isolates to first and second generation cephalosporins, a single dose of ceftriaxone plus metronidazole may be preferred over routine use of carbapenems Ertapenem is FDA-approved for prophylaxis in colorectal surgery It was more effective than cefotetan in one study, but it was associated with an increased risk of Clostridium difficile infection and other adverse effects (KM Itani et al N Engl J Med 2006; 355:2640) Routine use could promote carbapenem resistance Urine culture positive or unavailable, preoperative catheter, transrectal prostatic biopsy, or placement of prosthetic material Shock wave lithotripsy, ureteroscopy Including percutaneous renal surgery, procedures with entry into the urinary tract, and those involving implantation of a prosthesis If manipulation of bowel is involved, prophylaxis is given according to colorectal guidelines Divided into 100 mg before the procedure and 200 mg after For patients who are allergic to beta-lactams, clindamycin (900 mg IV) is a reasonable alternative Preoperative application of povidone-iodine to the skin and conjunctiva is recommended If a tourniquet is to be used during the procedure, the entire dose of antibiotic must be infused prior to its inflation GASTROINTESTINAL SURGERY — Prophylaxis is not recommended for routine gastroesophageal endoscopy or colonoscopy.11 Antimicrobial prophylaxis is recommended for patients undergoing esophageal or gastroduodenal procedures that involve entry into the GI lumen, such as resection for gastric carcinoma, percutaneous endoscopic gastrostomy (PEG) insertion, pancreatic duodenectomy, and perforated ulcer procedures For procedures that not involve entry into the GI tract, prophylaxis is recommended only for patients at increased risk for infection, including those with GI obstruction, increased gastric pH, decreased GI motility, gastric bleeding, malignancy, or perforation, morbid obesity, or immunosuppression Because the risk of postoperative infection is high in patients undergoing bariatric surgeries, such as adjustable gastric banding, vertical banded gastroplasty, Roux-en-Y gastric bypass, and biliopancreatic diversion, antibiotic prophylaxis is used 65 The Medical Letter ® routinely for these procedures, but no controlled trials are available The appropriate antimicrobial regimen is unclear, but higher doses of antibiotics may be needed to achieve adequate serum and tissue concentrations in morbidly obese patients.12 Antimicrobial prophylaxis is recommended before biliary tract surgery for patients at high risk for infection, including those >70 years old and those with acute cholecystitis, a non-functioning gallbladder, obstructive jaundice, or common bile duct stones Antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is recommended only if complete biliary drainage is unlikely to be achieved.11 Prophylactic antibiotics are generally not necessary for low-risk patients undergoing elective laparoscopic cholecystectomy.13 Antibiotic prophylaxis can decrease the incidence of infection after colorectal surgery For most patients, a combination of oral neomycin and either oral erythromycin or oral metronidazole should be given (after mechanical bowel preparation) in addition to IV prophylaxis Combined IV and oral prophylaxis is more effective than IV prophylaxis alone in preventing surgical site infection.14 Ertapenem has been approved by the FDA for prevention of infection after elective colorectal procedures, but many experts advise against using it routinely for this purpose; it may be considered for use in situations where a patient or an institution is known to have organisms resistant to other antimicrobials.14,15 Antimicrobial prophylaxis can decrease the incidence of infection after surgery for acute appendicitis.16,17 It has been shown to reduce infection rates in patients undergoing mesh hernioplasty or herniorrhaphy; the risk is higher with hernioplasty.18,19 GENITOURINARY SURGERY — Most experts not recommend antimicrobial prophylaxis before cystoscopy without manipulation in patients with sterile urine When cystoscopy with manipulation (dilation, biopsy, fulguration, resection, or ureteral instrumentation) is planned, the urine culture is positive or unavailable, or an indwelling urinary catheter is present, patients should either be treated to sterilize the urine before surgery or receive a single preoperative dose of an agent that is usually active against the likely microorganisms Antimicrobial prophylaxis decreases the incidence of postoperative bacteriuria and septicemia in patients with sterile preoperative urine undergoing transurethral prostatectomy and transrectal prostatic biopsies.20-22 Prophylaxis is also recommended for ureteroscopy, shock wave lithotripsy, percutaneous 66 Vol 58 (1495) May 23, 2016 renal surgery, and open laparoscopic procedures, and for placement of a urologic prosthesis (penile implant, artificial sphincter, synthetic pubovaginal sling, bone anchors for pelvic floor reconstruction).23 The efficacy of fluoroquinolones for prophylaxis in urologic procedures is well established, but resistance has emerged.24 Local resistance patterns, particularly of E coli, should guide appropriate selection of antimicrobials for genitourinary procedures GYNECOLOGIC AND OBSTETRIC SURGERY — Antimicrobial prophylaxis decreases the incidence of infection after vaginal or abdominal hysterectomy.25 Prophylaxis is also recommended for laparoscopic hysterectomy Antimicrobials can prevent infection after elective and non-elective cesarean section; giving the dose prior to the initial skin incision appears to be more effective than giving it after cord clamping.26 Antimicrobial prophylaxis can also prevent infection following elective abortion.27 HEAD AND NECK SURGERY — Prophylaxis with antimicrobials has decreased the incidence of surgical site infection after clean-contaminated oncologic head and neck operations that involve an incision through the oral or pharyngeal mucosa.28 Prophylaxis is not recommended for tonsillectomy or nasal septoplasty.29,30 NEUROSURGERY — Antibiotic prophylaxis can decrease the incidence of infection after craniotomy.31 It is also effective for spinal surgery The infection rate after conventional lumbar discectomy is low, but the consequences of postoperative infection at this site can be serious Infection rates are higher after prolonged spinal surgery or spinal procedures involving fusion or insertion of foreign material.32 Studies have shown lower infection rates with use of prophylactic antibiotics for implantation of permanent cerebrospinal fluid shunts and for placement of intrathecal pumps.33 The benefits of antimicrobial prophylaxis for ventriculostomy placement remain uncertain.34 OPHTHALMIC SURGERY — There is no consensus supporting a particular choice, route, or duration of antimicrobial prophylaxis for ophthalmic procedures, but preoperative application of povidone-iodine to the skin and conjunctiva has been shown to lower the incidence of endophthalmitis.35 Other prophylactic strategies include pre- and postoperative topical antibiotic eye drops, addition of antibiotics to the irrigating solution, and subconjunctival injections Use of intracameral injections is limited by lack The Medical Letter ® of commercial availability and potential toxicity if inaccurately dosed There is no evidence that prophylactic antibiotics are needed for procedures that not invade the globe ORTHOPEDIC SURGERY — Antistaphylococcal drugs administered prophylactically can decrease the incidence of both early and delayed infection after joint replacement.36 They also decrease the rate of infection when hip and other closed fractures are treated with internal fixation by nails, plates, screws, or wires, and in compound or open fractures.37-39 Whether prophylaxis should be given as a single dose or as multiple doses for up to 24 hours is unclear.38-40 Prophylaxis is also recommended for orthopedic spinal procedures with and without instrumentation.41 A retrospective review of patients undergoing arthroscopic surgery concluded that antibiotic prophylaxis is not indicated.42 THORACIC SURGERY — Antibiotic prophylaxis is recommended for thoracic surgery, but supporting data are sparse In one study, a single preoperative dose of cefazolin before pulmonary resection led to a decrease in surgical site infection, but not in pneumonia or empyema.43 Insertion of chest tubes for non-traumatic indications, such as spontaneous pneumothorax, does not require antimicrobial prophylaxis VASCULAR SURGERY — Preoperative prophylaxis decreases the incidence of postoperative surgical site infection after arterial reconstructive surgery on the abdominal aorta, vascular operations on the leg that include a groin incision, and amputation of the lower extremity for ischemia.44,45 Many experts also recommend prophylaxis for implantation of any vascular prosthetic material, such as grafts for vascular access in hemodialysis Prophylaxis is not indicated for carotid endarterectomy or brachial artery repair without prosthetic material Prophylactic antibiotics are not routinely recommended for baremetal stenting, but risk factors that may justify their use include repeat intervention within days, prolonged indwelling arterial sheath, prolonged procedure duration (>2 hours), presence of other infected implants, and immunosuppression Although the incidence of infection after stent graft procedures is low (