A 68-year-old woman is admitted to the hospital from home with acute onset, unrelenting, upper abdominal pain radiating to the back and nausea/vomiting. Her medical history includes bile duct obstruction secondary to gall stones, which was managed in another facility 6 days earlier with endoscopic retrograde cholangiopancreatography and stenting. The patient has type 2 diabetes (managed with metformin and glargine insulin), hypertension (managed with lisinopril and hydrochlorothiazide), and cholesterolemia (managed with atorvastatin).
On admission, the patient's white blood cell count is 14.7 x 103 cells/mm3, heart rate is 100 bpm, blood pressure is 90/68 mm Hg, and temperature is 101.5° F. Serum amylase and lipase are 3 and 2 times the upper limit of normal, respectively. A working diagnosis of acute pancreatitis with sepsis is made. Blood cultures are drawn. A computed tomography scan confirms acute pancreatitis. She receives one dose of meropenem, is started on intravenous fluids and morphine, and is transferred to the intensive care unit (ICU) for further management.
Her ICU course is complicated by worsening sepsis despite aggressive fluid resuscitation, nutrition, and broad-spectrum antibiotics. On post-admission Day 2, blood culture results reveal Escherichia coli that is resistant to gentamicin, amoxicillin/clavulanate, ceftriaxone, piperacillin/tazobactam, imipenem, trimethoprim/sulfamethoxazole, ciprofloxacin, and tetracycline. Additional susceptibility testing is ordered.
The Centers for Disease Control and Prevention (CDC) conservatively estimates that antibiotic-resistant bacteria are responsible for 2 billion infections annually, resulting in approximately 23,000 deaths and $20 billion in excess health care expenditures annually.1 Infections caused by antibiotic-resistant bacteria typically require longer hospitalizations, more expensive drug therapies, and additional follow-up visits.1 They also result in greater morbidity and mortality compared with similar infections involving non-resistant bacteria.1 To compound the problem, antibiotic development has steadily declined over the last 3 decades, with few novel antimicrobials developed in recent years.2 The most recently approved antibiotics with new mechanisms of action were linezolid in 2000 and daptomycin in 2003, preceded by the carbapenems 15 years earlier. (See “New antimicrobials in the pipeline.”)
New antimicrobials in the pipeline
The Generating Antibiotic Incentives Now (GAIN) Act was signed into law in 2012, creating a new designation—qualified infectious diseases products (QIDPs)—for antibiotics in development for serious or life-threatening infections (https://www.congress.gov/112/plaws/publ144/PLAW-112publ144.pdf). QIDPs are granted expedited FDA approval and an additional 5 years of patent exclusivity in order to encourage new antimicrobial development.
Five antibiotics have been approved with the QIDP designation: tedizolid, dalbavancin, oritavancin, ceftolozane/tazobactam, and ceftazidime/avibactam, and 20 more agents are in development including a new fluoroquinolone, delafloxacin, for acute bacterial skin and skin structure infections including those caused by methicillin-resistant Staphylococcus aureus (MRSA), and a new tetracycline, eravacycline, for complicated intra-abdominal infections and complicated UTIs. Eravacycline has in vitro activity against penicillin-resistant Streptococcus pneumoniae, MRSA, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacteriaceae, and multidrug-resistant A. baumannii. Both drugs will be available in intravenous and oral formulations.
Greater efforts aimed at using antimicrobials sparingly and appropriately, as well as developing new antimicrobials with activity against multidrug-resistant pathogens, are ultimately needed to address the threat of antimicrobial resistance. This article describes the evidence-based management of inpatient infections caused by resistant bacteria and the role family physicians (FPs) can play in reducing further development of resistance through antimicrobial stewardship practices.