Medicolegal Issues

Medication Compliance, the New C. Diff


The Tricky Nature of Medication Compliance

Review by Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med. 2005;353:487-497.

Adherence to (or compliance with) a medication regimen is generally defined as the extent to which patients take medications as prescribed by their healthcare providers. Adherence rates are typically higher among patients with acute conditions, as compared with those with chronic conditions; persistence among patients with chronic conditions is disappointingly low, dropping most drastically after the first six months of therapy. Of all medication-related hospital admissions in the United States, 33% to 69% are because of poor medication adherence, with a resultant cost of approximately $100 billion a year.

Electronic medication-monitoring devices have provided very detailed information about the patterns of medication-taking behavior. Studies using these monitors have shown six general patterns of taking medication among patients treated for chronic illnesses who continue to take their medications. Approximately one-sixth come close to perfect adherence to a regimen; one-sixth take nearly all doses, but with some timing irregularity; one-sixth miss an occasional single day’s dose and have some timing inconsistency; one-sixth take drug holidays three to four times a year, with occasional omissions of doses; one-sixth have a drug holiday monthly or more often, with frequent omissions of doses; and one-sixth take few or no doses while giving the impression of good adherence.

Poor adherence to medication regimens is common, contributing to substantial worsening of disease, death, and increased healthcare costs. Practitioners should always look for poor adherence and can enhance adherence by emphasizing the value of a patient’s regimen, making the regimen simple, and customizing the regimen to the patient’s lifestyle. Asking patients nonjudgmentally about medication-taking behavior is a practical strategy for identifying poor adherence. A collaborative approach to care augments adherence. Patients who have difficulty maintaining adequate adherence need more intensive strategies than do patients who have less difficulty with adherence, a more forgiving medication regimen, or both. Innovative methods of managing chronic diseases have had some success in improving adherence when a regimen has been difficult to follow.

Of all medication-related hospital admissions in the United States, 33% to 69% are caused by poor medication adherence, with a resultant cost of approximately $100 billion a year.

The New Clostridium Difficile—What Does It Mean?

McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxic gene-variant of Clostridium difficile. N Eng J Med. 2005;353;2433-2441.

Clostridium difficile is the only anaerobe that causes nosocomial infections. It colonizes the colon in 3% of the healthy population and about 20% to 40% of hospitalized patients.

This study was done in response to reports of increasing rate and severity of this infection. This study looked at healthcare facilities in Pennsylvania, Maine, Georgia, Oregon, Illinois, and New Jersey and did indeed find a new strain of Clostridium difficile isolate which showed 100% resistance to gatifloxacin and moxifloxacin, compared with no resistance in the historic strain.

Resistance to clindamycin was similar in both the groups, which was measured at 79%. This particular strain secretes 16 to 23 times more toxins A and B in vitro than other strains. And in this study the new strain accounted for 51% of the infections compared with 17% in the historic control isolates. Fluoroquinolones were implicated alone or in combination with other antibiotics in 52% of the cases. Those infected with the new strain were more likely to have higher rates of toxic megacolon, need for colectomy, leukemoid reaction, shock, and death. Like any disease, the interaction between host and pathogen is key to severity, thereby making patients who are chronically ill and elderly more susceptible.

For hospitalists the implications for this study are certainly important. We need to be aware of whether this strain is prevalent in our work environment. Close collaboration with our colleagues from infectious disease services along with monitoring clinical outcomes of patients with Clostridium difficile infection is the need of the hour. Also recommended is investigation of any increases in caseload of this infection. Simple measures such as judicious use of antibiotics, early diagnosis, and appropriate treatment of Clostridium difficile infection and strict isolation of the patients infected or colonized with Clostridium difficile would go a long way in controlling the spread of the new more virulent strain. It must be pointed out that alcohol-based waterless hand-sanitizing agents do not kill the Clostridium difficile spores; washing hands with soap and water is a prudent option after coming in contact with a patient with Clostridium difficile. TH

Classic Literature

Measuring Quality in the ’60s

Schimmel EM. Hazards of Hospitalization. Ann Int Med. 1964;60:100-110.

“The occurrence of hospital-induced complications on a university medical service was documented in the prospective investigation of over 1,000 patients. The reported episodes were the untoward consequences of acceptable medical care in diagnosis and therapy. During the eight-month study, 240 episodes occurred in 198 patients. In 105 patients, hospitalization was either prolonged by an adverse episode or the manifestations were not yet resolved at the time of discharge. Thus, 20% of the patients admitted to the medical wards experienced one or more untoward episodes and 10% had a prolonged or unresolved episode. The severity of 240 episodes was minor in 110, moderate in 82, major in 48, of which 16 ended fatally. Patients encountering noxious episodes had a mean total hospitalization of 28.7 days, compared with 11.4 days in other patients. The risk of having such episodes was directly related to the length of time spent in the hospital. The number and variety of these reactions emphasizes the magnitude and scope of hazards to which the hospitalized patient is exposed. A judicious selection of diagnostic and therapeutic measures can be made only with the knowledge of these potential hazards as well as the proposed benefits.”

Dr. Schimmel was the chief resident at Yale from 1960 to 1961. It is during that period that he designed the research project. This report stands out as a landmark study in the measurement of quality of care. The study was done at a time when economics of healthcare did not grab headlines, the average cost of one day of hospitalization was under $70, and medicine was practiced with a “doctor knows best” attitude.

One of the most important findings from this study was that the adverse events did not, by themselves, account for the increased length of stay. In fact, the prolonged hospitalization predisposed patients to higher adverse events—a fact that was nothing short of a revelation. Physicians were now forced to consider risk of hospitalization as a factor in deciding whether an admission was warranted for medical care.

Dr. Schimmel’s study pointed out that, with increasing severity of illness, patients received more diagnostic tests and therapeutic interventions, thereby increasing the risk for adverse events. The study also brought into focus the need to discuss and analyze the overall risk–benefit ratio for each procedure or intervention. One of the drawbacks of this study is that it did not take into account adverse events from medical errors. One can only speculate that the actual percentage of adverse events might have been higher than 20%.

A similar study that looked at iatrogenic adverse events done at Boston University Medical Center in 1979 revealed an adverse event rate of 36%. With increasing complexity of medical care, an aging population base (the average age of the patient in Dr. Schimmel’s study was 53), and less-than-ideal information management, this study remains a beacon to all of us who are committed to the principle of “do no harm.”

A system of voluntary reporting of all adverse events, including those from medical errors, should be developed and information shared by all the stakeholders (including patients and their families) in an effort to ameliorate the hazards of hospitalization. To this end the Institute of Healthcare Improvement’s “100K Lives” campaign brings much needed attention on this important issue.—SS


  • Qual Saf Health Care. 2003;12:58-63; discussion 63-64.
  • Steel K, Gertman PM, Crescenzi C, et al. Iatrogenic illness on a general medical service in a university hospital. N Eng J Med. 1981;304:638-642.

Nasal MRSA Carriage: A Study of Current Prevalence with Commentary

Creech CB, Kernodle DS, Alsectzer M, et al. Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus in healthy children. Pediatr Infect Dis J. 2005;24:617-621.

Review by Laura Ortman, MD

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections seen in outpatient clinics and emergency rooms appears to be on the rise. In 2001 a study done at Vanderbilt University Medical Center found the prevalence of MRSA in its pediatric community to be 0.8%1. Creech, et al., devised a study to describe the current prevalence of MRSA colonization in the same population.

The study population was children between the ages of two weeks and 21 years of age presenting for a health maintenance visit at two outpatient clinics. Nasal swabs were obtained and cultures preformed on plates with and without oxacillin containing media. Possible MRSA isolates were confirmed with PCR for the mecA gene, which codes for the protein responsible for beta-lactam resistance.

Of the 500 children enrolled 182 (36.4%) were found to be colonized with S. aureus. 46 (9.2%) isolates were positive for the mecA gene and considered MRSA. The only risk factor found to increase risk for MRSA colonization was having a family member who works in a hospital (odds ratio, 2.0; 95% confidence interval, 1.03-4.1). Fifty-four percent of MRSA isolates were resistant to erythromycin, and 32% of these had inducible clindamycin resistance.

Commentary: This study shows a greater than tenfold increase in MRSA colonization in a three-year time period in a healthy outpatient population. This finding is consistent with other studies that have shown increasing rates of colonization.2-3 This increase has led some institutions to attempt decolonization of MRSA, most often using nasal mupirocin. To determine if current evidence supports attempts to eradicate MRSA nasal colonization, the following literature search was performed: Cochrane DSR, ACP Journal Club, PubMed, and PubMed Clinical Queries were searched using the search terms “MRSA,” “colonization,” and “staphylococcus.”

One Cochrane review summarizes the evidence for use of antimicrobial agents on MRSA colonized patients4. Of six randomized controlled trials, only one compares rates of infection during follow-up between the study and control groups. The difference in infections was not statistically significant. Five other studies of inconsistent quality followed eradication rates of MRSA and varied widely in their results. The Cochrane review concluded that there was insufficient evidence to recommend nasal decolonization of MRSA.

One article reviewed the evidence for intranasal mupirocin for S. aureus.5 This review did not differentiate between MRSA and MSSA. The authors appraised clinical trials that evaluated the effect of mupirocin on MRSA colonization and infection. In a trial of patients undergoing dialysis there was no overall difference in the rate of infection between groups. In trials using mupirocin for preoperative prophylaxis there was no difference in number of surgical site infections. The authors concluded that mupirocin did not result in long-term clearance of S. aureus and that the available evidence does not support its use for prevention of infection. With the current evidence routine decolonization of patients colonized with MRSA cannot be recommended.


  1. Nakamura MM, Rohling KL, Shashaty M, et al. Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in the community pediatric population. Pediatr Infect Dis J. 2002;21:917-922.
  2. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998;279:593-598.
  3. Fergie JE, Purcell K. Community-acquired methicillin-resistant Staphylococcus aureus infections in south Texas children. Pediatr Infect Dis J. 2001;20:860-863.
  4. Loeb M, Main C, Walker-Dilks C. Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization. Cochrane Database Syst Rev. 2003;(4):CD003340.
  5. Laupland KB, Conly JM. Treatment of Staphylococcus aureus colonization and prophylaxis for infection with topical intranasal mupirocin: an evidence-based review. Clin Infect Dis. 2003;37:933-938.
Ultrasound may still be the appropriate initial study for the majority of children presenting with symptoms suggestive of urolithiasis.

Is Ultrasound Sufficient for Diagnosing Urolithiasis in the Pediatric Patient?

Palmer JS, Donaher ER, O’Riordan MA, et al. Diagnosis of Pediatric Urolithiasis: Role of ultrasound and computerized tomography. J Urol. 2005;174:1413-1416.

Review by Ann Mattison, RN, CPNP

Pediatric urolithiasis is uncommon and may present without the classic symptoms of renal colic, making diagnosis of pediatric urolithiasis problematic. Previously published data has revealed that unenhanced spiral CT is the gold standard in diagnosing urinary tract calculi in adults. However, CT carries the risk of exposure to ionizing radiation, which can be a significant issue in children.

Due to the low prevalence of urolithiasis in addition to concerns about radiation exposure, many primary care providers choose ultrasound as the initial radiographic study for children with symptoms that can be associated with urolithiasis, such as flank pain, abdominal pain, and gross hematuria. But the accuracy of ultrasound in detecting pediatric urolithiasis has not been well studied.

A retrospective chart review was performed in all patients 0-18 evaluated as outpatients and inpatients at the study institution. Subjects were identified by ICD-9 codes and billing records. The study showed the accuracy of ultrasounds performed was variable and dependent on the location of the calculi. In contrast, CT was highly accurate regardless of calculi location.

The study concluded that ultrasound may still be the appropriate initial study for the majority of children presenting with symptoms suggestive of urolithiasis; however, a negative ultrasound should not be considered sufficient to rule out the diagnosis of urolithiasis in pediatric patients. The authors recommended the patient with persistent symptoms and negative ultrasound undergo unenhanced CT. The retrospective design of this study limits application of these results; however, the study does highlight the need for a heightened index of suspicion for the diagnosis as well as the need for further prospective studies describing the most safe and efficient method for confirming the diagnosis. TH

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