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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
July 14, 2012

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Gabapentin for Cannabis Dependence
People Gain an Average of 10 Pounds 1 Year After Quitting Smoking
Meta-Analysis: Cranberries Offer Protection Against UTIs
Adult Stem Cell Therapy Treats Osteoarthritis in Mice
Can Botulinum Toxin Improve Disabling Tremor Caused by Multiple Sclerosis?
Excedrin Recall Impacts Migraine Sufferers
For Infants, Dogs in the Home Bring Respiratory-Tract Rewards
20% of Women Who Have Breast-Conserving Surgery Will Need Another Operation
Metformin for Antipsychotic-Induced Adverse Effects in Women with Schizophrenia
Reducing Risk for Rapid Repeat Pregnancy in Adolescents
Poor Dental Health Affects School Performance and Psychosocial Well-Being
The Search for the Perfect Diet Continues
Reducing the Length of Hospital Stay in Patients with Community-Acquired Pneumonia
The Fitness Cost of Drug Resistance

MM: Here is another example of the benefits of being able to use a prescription for an “off label use”. Similar to the use of HCG for weight loss or the use of aspirin for post stroke patients or phenobarbital for seizure disorders, the practice of allowing clinicians to use a drug product for off label uses is one that should be sacrosanct and not denied. Allow the practitioners to determine how to practice medicine and not the FDA or the politicians.
  
Neuropsychopharmacology 2012 Jun; 37:1689
Gabapentin for Cannabis Dependence
Commonly used for seizures, pain, and anxiety, gabapentin shows broad spectrum effects in patients with cannabis dependence.
Cannabis dependence is responsible for a quarter of all inpatient substance use admissions globally and is associated with prominent cognitive, work, and social dysfunctions. Several medications with different mechanisms of action have been found ineffective against cannabis dependence. Researchers conducted a pilot, 12-week, randomized, placebo-controlled trial to test the efficacy of gabapentin (1200 mg, given in 3 divided doses daily) in 50 patients with long-standing, chronic cannabis dependence (mean age at first use, 14.5 years; mean daily use, 11.6 years). All participants received motivational enhancement and counseling using techniques from cognitive-behavioral therapy. The researchers' institution has applied for a patent for this application of gabapentin.
  
Compared with placebo, gabapentin was associated with greater reductions in amount and days of use, withdrawal symptoms, craving, and psychological and physical problems related to use, and with greater improvements in executive cognitive dysfunction (studied in the last 38 enrollees). Groups showed no differences in adverse events. Of enrollees, 64% dropped out; at baseline, dropouts had earlier onset of use, more chronic use, greater withdrawal symptoms, and greater cognitive dysfunction.
  
Comment: Gabapentin, a very well-tolerated medication, may add significant benefit to drug counseling in cannabis-dependent patients, a cohort for whom there are no established medication treatments (see also JW Psychiatry Jul 2 2012). Higher doses could well improve efficacy, but the effect found in this study is impressive because gabapentin had benefits over and above those from effective counseling. The high dropout rate is typical for addiction studies. Clinicians treating patients with cannabis dependence could try this medication right now.
Peter Roy-Byrne, MD Published in Journal Watch Psychiatry July 2, 2012
  
Citation(s): Mason BJ et al. A proof-of-concept randomized controlled study of gabapentin: Effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults. Neuropsychopharmacology 2012 Jun; 37:1689
http://www.ncbi.nlm.nih.gov/pubmed/22373942?dopt=Abstract
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People Gain an Average of 10 Pounds 1 Year After Quitting Smoking
One year after quitting smoking, people have gained an average of 10 lb, according to a meta-analysis in BMJ.
  
Researchers analyzed 62 randomized trials that measured weight gain following smoking cessation. Regardless of the cessation treatment used, all groups gained about 2 lb per month for the first 3 months. Then, weight gain slowed until 1 year, at which point people had gained an average of 9 to 11 lb. However, there was a large variation in weight change — about 16% of participants lost weight, while about 13% gained more than 22 lb.
  
Editorialists caution that the results may not be generalizable to all smokers because these participants volunteered for cessation clinics. They conclude: "Although obesity is positively associated with an increased risk of all cause mortality, cohort studies indicate that modest weight gain does not increase the risk of death; smoking does."
http://www.bmj.com/content/345/bmj.e4439
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MM: Previous studies have demonstrated that cranberries were inferior to SMZ-TMP (Sulfamethoxazole-Trimethoprim) in the treatment of UTI’s but there is NO Bacterial Resistance that develops with cranberry or D-mannose extract (the active ingredient in cranberries). I have been a long time supported of the use of D-mannose for uncomplicated UTI’s associated with E. Coli infection – the most common couse of UTI’s. This is has been an especially useful product with small children and people with in-dwelling catheters.
  
Meta-Analysis: Cranberries Offer Protection Against UTIs
Cranberry intake appears to lower the risk for urinary tract infections, according to a meta-analysis in the Archives of Internal Medicine.
  
In 13 randomized controlled trials comprising some 1600 participants, those consuming cranberry products showed a roughly 30% lower rate of urinary tract infection than controls. The effect was most notable in women with recurrent infections (relative risk, 0.53), female populations (0.49), and children (0.33). The authors urge "great caution" in interpreting their analysis, given the heterogeneity found among study designs.
  
Long used as a folk preventive for urinary tract infections, cranberries were thought to exert their protective effect through urinary tract acidification. That notion, the authors write, was disproved a half century ago. Current explanations include cranberries' effect on limiting the ability of bacteria to attach to uroepithelial cells.
http://archinte.jamanetwork.com/article.aspx?articleid=1213845
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MM: This is some of the most potentially far-reaching research yet on a life-tormenting condition and the use of stem cells. What is especially exciting is that these stem cells are derived from mature tissue. More exciting is the possibility of harvesting them from the individual host and re-implanting them like what is sometimes done with self-donation of blood in preparation for surgery. This can virtually eliminate the potential for rejection and associated problems when cells or organs are obtained from outside donors. The result could be the virtual elimination of anti-rejection drugs for post treatment. This means that recipients could have little or no diminished effect of their immune systems and post-treatment costs would be greatly diminished.
  
Science 2012 May 11; 336:717
Adult Stem Cell Therapy Treats Osteoarthritis in Mice
Kartogenin promotes formation of new cartilage.
In osteoarthritis (OA), chondrocytes are deficient in either number or function: Replacing degraded joint cartilage matrix is inadequate. Studies have shown that adult mesenchymal stem cells (MSCs), which are found in damaged cartilage, can develop into chondrocytes, but researchers had not found ways to encourage that transformation. As a result, the only two therapies for patients with symptomatic OA are analgesics and joint surgery.
  
U.S. investigators now report the discovery of kartogenin, a small molecule that promotes differentiation of MSCs into chondrocytes in vitro. The team also identified the biochemical pathway by which kartogenin works and tested intra-articular administration of kartogenin in two mouse models of OA. In such mice, the number of chondrocytes increased, cartilage matrix was restored, and serum markers of cartilage degradation dropped. In standardized tests, the treated mice were better able to perform functions that relied on functional and relatively pain-free joints. No adverse effects of treatment were noted.
  
Comment: In this industry-funded study, investigators report on a molecule that stimulates the formation of new cartilage in mouse joints that have been ravaged by osteoarthritis. As most U.S. citizens older than 55 suffer from OA, the efficacy of this molecule in humans surely will be explored.
Anthony L. Komaroff, MD Published in Journal Watch General Medicine June 12, 2012
  
Citation(s): Johnson K et al. A stem cell–based approach to cartilage repair. Science 2012 May 11; 336:717.
(http://dx.doi.org/10.1126/science.1215157)
http://www.ncbi.nlm.nih.gov/pubmed/22491093?dopt=Abstract
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Neurology 2012 Jul 3; 79:92
Can Botulinum Toxin Improve Disabling Tremor Caused by Multiple Sclerosis?
Ability to write, drink, and pour was improved in this placebo-controlled crossover trial.
Tremor can be a disabling and frustrating symptom in multiple sclerosis (MS). No treatment with a lasting and consistent functional benefit has been identified, despite much research. Now, investigators have tested the effect of botulinum toxin (BT) in 23 people with mostly moderate, upper-extremity tremor of posture, action, and intentional movement caused by MS, in a randomized, double-blind, crossover trial. Participants received BT injections directed toward agonist and antagonist muscles related to specific tremor patterns.
  
At baseline, participants had good proximal and distal upper-limb strength (median Medical Council Rating, 5; interquartile range, 4.5–5.0) and high Expanded Disability Status Scale scores (median, 5.5; interquartile range, 4.0–6.5). Most (74%) had secondary-progressive MS; 26% had relapsing–remitting MS. At 6 and 12 weeks, median scores for tremor, writing, and spiral drawing improved in the BT-injection group but did not change in the placebo group; the between-group differences were significant. The BT group also improved on the 9-hole peg test and drinking from a cup at 12 weeks, and pouring at 6 weeks. Quality-of-life scores did not change significantly. Adverse reactions included up to 2 weeks of weakness, which was mild (minimally detectable, not interfering with function) in 4 participants (2 after BT injection, 2 after placebo injection) and moderate (present but not interfering with most activities) in 12 participants after BT.
  
Comment: This study provides commendable preliminary results that a trial of botulinum toxin may be considered for upper-limb multiple sclerosis tremor. Study strengths include blinding, a placebo arm, quantitative functional assessments at up to 3 months, and primary funding independent from BT manufacturers (who were involved only by donating 40 vials of the therapy). The authors say their findings support modulation of stretch-elicited peripheral feedback, not weakening of the limb, as the mechanism of benefit in MS tremor. Although the treatment may not result in functional improvement for everyone, clinicians might consider it for MS patients with isolated tremors and preserved upper-extremity strength.
Robert T. Naismith, MD Published in Journal Watch Neurology July 10, 2012
  
Citation(s): Van Der Walt A et al. A double-blind, randomized, controlled study of botulinum toxin type A in MS-related tremor. Neurology 2012 Jul 3; 79:92.
http://www.ncbi.nlm.nih.gov/pubmed/22753445?dopt=Abstract
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MM: While Excedrin® in unavailable on store shelves, Mark Drugs is able to compound this product for patients who need it. Please call us so that we may meet your medication needs.
Excedrin Recall Impacts Migraine Sufferers
Store shelves are Excedrin-free, and Novartis has attributed the recall and shortage to problems at its Nebraska plant that could have led to contamination by other medications produced there. Novartis has previously announced a massive recall of its Excedrin, No-Doz, Bufferin, and Gas-X products. The company says it is working very hard to return products to store shelves and plans to restart production on a "line-by-line, product-by-product basis" to assure quality, and hopes to start restocking some products in the second half of the year. They did not mention which of the recalled products will be manufactured first. Some patients are turning to eBay to purchase whatever stock is available at hugely inflated prices, and some medications are passed around by private individuals. Each Excedrin Migraine consists of 250 milligrams of aspirin, 250 milligrams of acetaminophen (Tylenol), and 65 milligrams of caffeine. A generic substitute could work just as well.
http://abcnews.go.com/Health/migraine-sufferers-scrambling-months-excedrin-migraine-recall/story?id=16743173#.T_w9U3B4X35
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For Infants, Dogs in the Home Bring Respiratory-Tract Rewards
Children with dogs in the home during the first year of life have fewer respiratory infections during that period, according to a Pediatrics study.
  
Researchers followed some 400 children in Finland between the ages of 9 and 52 weeks. Parents filled out weekly diaries, recording how much time household pets generally spent in the house and detailing any infections their children experienced. At 1 year, the data revealed that, compared with children in households with no pets, those in homes with dogs were more likely to be healthier overall (odds ratio, 1.31), have less frequent middle ear infections (OR, 0.56), and less need for antibiotics (OR, 0.71). Cats were associated with similar protective effects, but not as strongly.
  
The authors speculate that pets could help speed maturation of the immune system in infants, leading to better immunologic responses and shorter duration of infections.
http://pediatrics.aappublications.org/content/early/2012/07/03/peds.2011-2825.abstract
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20% of Women Who Have Breast-Conserving Surgery Will Need
Another Operation

One in five women who undergo primary breast-conserving surgery for invasive breast cancer or carcinoma in situ will require another operation within 3 months — highlighting the need to counsel women about reoperation rates and the odds of eventually needing a mastectomy — researchers conclude in BMJ.
  
Some 55,000 women who underwent breast-conserving surgery in the U.K. over a 3-year period were included in the analysis. Of these, 20% required at least one additional operation (either further breast-conserving surgery or mastectomy) within 3 months of the primary procedure. In addition, of those who underwent a second breast-conserving surgery, 14% required a third operation.
  
Overall, women with carcinoma in situ were significantly more likely to require a follow-up operation than were those with invasive disease only (30% vs. 18%)
http://www.bmj.com/content/345/bmj.e4505
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Am J Psychiatry 2012 Jun 15
Metformin for Antipsychotic-Induced Adverse Effects in Women with Schizophrenia
The medication reversed amenorrhea, promoted weight loss, and improved insulin resistance.
Metformin has been used successfully to treat polycystic ovary syndrome (PCOS), restore menstruation in amenorrheic obese women, and improve antipsychotic-associated weight gain and insulin resistance in schizophrenia patients. Based on these observations, investigators in China examined effects of metformin in 84 physically healthy, non–substance-abusing outpatients experiencing amenorrhea in their first year of treatment for first-episode schizophrenia.
  
Weight gain of greater than 10%, measured from initiation of antipsychotic treatment to study entry, occurred in 70% of patients. Antipsychotics were clozapine, olanzapine, risperidone, or sulpiride; doses were relatively stable for the preceding 6 months. In a randomized, double-blind protocol, patients received metformin (1000 mg/day) or placebo plus their antipsychotic medications for up to 6 months.
  
Menstruation resumed in 66.7% of metformin recipients (within 3 months of starting metformin) and in 4.8% of placebo recipients — a significant difference. Significantly more metformin recipients than placebo recipients lost more than 10% of their baseline weight (28.6% vs. 2.4%) by 6 months. Mean insulin resistance index and levels of insulin, prolactin, and luteinizing hormone also decreased significantly with metformin compared with placebo. Normalization of weight, insulin resistance, and levels of prolactin and luteinizing hormone contributed to the increased probability of return of menses.
  
Comment: Symptoms of polycystic ovary syndrome, occurring in about 7% of all women, can involve weight gain and amenorrhea, and metformin's mechanisms of action on PCOS and on antipsychotic-induced metabolic effects are likely to be related. Conceivably, PCOS was present in clinical or preclinical forms in many of these patients. Given the drug's low adverse effect profile, prescribing metformin to treat amenorrhea and other antipsychotic-induced adverse metabolic effects may start to fall within the psychiatrist's routine scope of practice.
Joel Yager, MD Published in Journal Watch Psychiatry July 9, 2012
  
Citation(s): Wu R-R et al. Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: A double-blind, randomized, placebo-controlled study. Am J Psychiatry 2012 Jun 15; [e-pub ahead of print].
(http://dx.doi.org/10.1176/appi.ajp.2012.11091432)
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MM: It seems that the ACOG is once again in the business of trying to affect public policy on contraception.
  
Am J Obstet Gynecol 2012 Jun; 206:481.e1
Reducing Risk for Rapid Repeat Pregnancy in Adolescents
Immediate postpartum implant placement dramatically lowered incidence of repeat pregnancy.
Despite recognition of the hardships created by rapid repeat teen pregnancy, prevention remains challenging. In this prospective cohort study, investigators compared rates of repeat pregnancy within 12 months after delivery among 171 adolescent mothers who underwent immediate postpartum implant placement (before hospital discharge) and 225 who pursued other contraceptive strategies.
  
The comparison group included 3 adolescents who underwent tubal ligation and 86 who used intrauterine devices or implants within 1 year of giving birth; 42.7% had some form of long-acting contraception in place within 6 months of delivery. Nonetheless, adolescents who did not receive immediate postpartum implants had 5 times the risk for pregnancy within 12 months compared with those who received implants (18.6% vs 2.6%).
  
Comment: Although adolescents who opt for immediate implant placement generally differ in other ways from those who do not, if a randomized trial yielded results similar to the present findings, the number needed to treat to prevent one rapid repeat pregnancy would be six. In light of recent findings that the contraceptive implant does not raise risk for thromboembolism (JW Womens Health May 24 2012) or adversely affect lactation (JW Womens Health May 12 2011), immediate postpartum implant placement should be routinely offered to adolescent mothers. Hospitals and insurance companies that do not support postpartum implant insertion prior to discharge should reconsider their policies.
Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health June 21, 2012
  
Citation(s): Tocce KM et al. Rapid repeat pregnancy in adolescents: Do immediate postpartum contraceptive implants make a difference? Am J Obstet Gynecol 2012 Jun; 206:481.e1. (http://dx.doi.org/10.1016/j.ajog.2012.04.015)
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MM: It often seems that a lack of insurance coverage will act as a significant barrier to healthcare. This is especially the case when it comes to ignoring proper dental care. Since most insurance coverage ignores this area or offers extremely limited or poor coverage many parents fail to bring their children to the dentist. Unfortunately this seems to stem from a lack of knowledge on the part of the parents in the first place. This is a self perpetuating issue and we need to look at the options needed to improve mouth care as the mouth has an effect on all organ systems and health
  
J Pediatr 2012 Jun 23;
Poor Dental Health Affects School Performance and Psychosocial Well-Being
Children with dental problems had more problems in school and were more likely to feel worthless or inferior, shy, and unhappy or depressed than children without dental problems.
Dental problems are among the most common pediatric health conditions globally and have been associated with both medical and developmental consequences. Researchers evaluated the relation between dental problems (toothache, cavity, or bleeding gums) and school performance and psychosocial well-being in more than 45,000 school-aged children (age range, 6–17 years) in the 2007 National Survey of Children's Health.
  
Approximately 30% of children had a dental problem, 30% had problems in school, and 10% of mothers rated their child's dental health as fair or poor. In multivariate analysis that was adjusted for socioeconomic and other potential confounders, children with dental problems were significantly more likely than children without dental problems to have problems at school (odds ratio, 1.52), miss school (OR, 1.42), and not do all required homework (OR, 0.76). On average, children with dental problems missed one additional school day per year than children without dental problems. Children with dental problems were also significantly more likely to feel worthless or inferior (OR, 1.39); shy (OR, 1.34); unhappy, sad, or depressed (OR, 1.31); and to be less friendly (OR, 0.86) than their counterparts.
  
Comment: Dental health affects school performance and psychosocial well-being in addition to general health. Primary care pediatric clinicians need to perform good oral examinations and work with dentists to promote oral health.
F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine July 11, 2012
  
Citation(s): Guarnizo-Herreño CC and Wehby GL. Children's dental health, school performance, and psychosocial well-being. J Pediatr 2012 Jun 23; [e-pub ahead of print].
(http://dx.doi.org/10.1016/j.jpeds.2012.05.025)
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MM: There will always be criticism of anything that challenges the existing paradigm. From Michelangelo to Galileo, authority has worked to protect itself and maintain its authority. This is no different in medicine or nutrition. We stay married to our positions even when they are not wholly correct. Here we see the headline that low carb/high protein is bad but what we ignore is that the epidemic of obesity greatly outweighs any negative inpact the food mix may show.
  
BMJ 2012 Jun 26; 344:e4026
The Search for the Perfect Diet Continues
A Swedish study suggests that the long-term cardiovascular consequences of a low-carb, high-protein diet are negative.
Short-term, rapid weight loss has made Atkins-type, low-carbohydrate, high-protein diets popular, but concerns about the long-term effects of these diets continue to mount. In a large, population-based sample of 43,396 Swedish women aged 30 to 49 who completed a dietary questionnaire, investigators assessed the impact of low carbohydrate intake, high protein intake, or both on cardiovascular outcomes during an average follow-up of 15.7 years.
  
Each 10% decrease in carbohydrate intake (20 g — a small roll — per day), each 10% increase in protein intake (5 g — one boiled egg — per day), or each 2-unit increase in low-carbohydrate/high-protein score (scale: 2–20, with 20 representing very low carbohydrate and very high protein intake) was associated with a significant 4%–5% increase in the risk for cardiovascular events. In absolute terms, this represents an additional eight or nine cardiovascular events per 10,000 patient-years in women with low-carbohydrate/high-protein scores of 16 or more, as compared with those with scores of 6 or less.
  
Comment: Although these findings suggest that low-carbohydrate, high-protein diets are associated with increased risk for cardiovascular disease, the effect size is small, and multiple confounders are probably in play. Until stronger evidence definitively identifies a harm — or benefit — of a particular approach, the best heart-healthy diet is probably one of overall moderation in which calories consumed are balanced with calories expended.
JoAnne M. Foody, MD Published in Journal Watch Cardiology July 11, 2012
  
Citation(s): Lagiou P et al. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: Prospective cohort study. BMJ 2012 Jun 26; 344:e4026.
(http://dx.doi.org/10.1136/bmj.e4026)
http://www.ncbi.nlm.nih.gov/pubmed/22735105?dopt=Abstract
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MM: In the musical Cabaret there is a song, Money Makes the World Go Around. There appears to be no statement truer than this when it comes to changing a paradigm in healthcare. Here we see a reduction in hospital stay of about 35% resulting in lower costs and improved patient care coming about due largely to the abyssmal condition of the Spanish economy.
  
Arch Intern Med 2012 Jun 25; 172:922.
Reducing the Length of Hospital Stay in Patients with
Community-Acquired Pneumonia

In a randomized, controlled trial, use of a three-step critical pathway reduced the durations of intravenous antibiotic therapy and hospitalization without increasing deaths or readmissions.
Today's focus on healthcare expenditures has prompted renewed interest in examining clinical practice and methods to maintain safety and improve outcomes while reducing costs. Various tools have been developed to alter clinician behavior, where needed, to achieve these goals. Investigators recently conducted a prospective, randomized trial at two tertiary care hospitals in Spain to evaluate the effect of a critical pathway on management and outcomes of patients with community-acquired pneumonia (CAP). The pathway had three steps:

Immunocompetent adults who were diagnosed with CAP in the emergency department were randomized to follow the three-step critical pathway or to receive usual therapy. Empirical therapy administered in the emergency department included a β-lactam with or without a macrolide or fluoroquinolone; combination therapy was recommended for patients with severe CAP. Levofloxacin was administered as monotherapy in select patients and those with legionellosis.
  
A total of 401 patients were randomized and included in the intent-to-treat analyses. Median hospital length of stay was 3.9 days in the 3-step group versus 6.0 days in the usual-care group (difference, –2.1 days; 95% confidence interval, –2.7 to –1.7). Reductions were also seen in median duration of intravenous antibiotic therapy (2.0 days vs. 4.0 days; difference, –2.0 days; 95% CI, –2.0 to –1.0) and rate of adverse drug reactions (4.5% vs. 15.9%; difference, –11.4 percentage points; 95% CI, –17.2 to –5.6 percentage points). Thirty-day readmission rates, 30-day all-cause death rates, and patient satisfaction were similar between groups.
  
Comment: Changing clinicians' behavior is difficult. As noted in an accompanying editorial, achieving even small changes in physician behavior with tools that include a critical pathway for managing CAP could result in impressive reductions in healthcare expenditures without sacrificing outcomes or patient satisfaction.
Larry M. Baddour, MD Published in Journal Watch Infectious Diseases July 11, 2012
  
Citation(s):Carratalà J et al. Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: A randomized controlled trial. Arch Intern Med 2012 Jun 25; 172:922.
http://www.ncbi.nlm.nih.gov/pubmed/22732747?dopt=Abstract
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MM: This may be a reason to hold back on the use of antibiotics, improve overall hygiene and not panic when antibiotic resistant strains come into play. It appears that the resistant strains may play theselves out under certain conditions.
  
J Antimicrob Chemother 2012 Jun; 67:1325
The Fitness Cost of Drug Resistance
The high fitness cost associated with multidrug resistance may help to explain the decrease in MRSA infections currently seen in Denmark and some other countries.
During the 1960s in Denmark, the proportion of Staphylococcus aureus blood culture isolates that were methicillin resistant (MRSA) increased rapidly, from <1% to >30%. S. aureus phage type 83A was the dominant staphylococcal blood isolate during that period, and 70% of such isolates were multidrug resistant. By 1980, the proportion of S. aureus blood isolates with methicillin resistance had dropped significantly, to <2%, paralleled by a significant decline in S. aureus phage type 83A. Improved hospital hygiene and changes in antibiotic policy have been proposed as explanations for the reduction, but the exact reasons remained unclear.
  
To explore this issue, researchers examined the relative fitness of 40 phage type 83A blood isolates (with and without methicillin resistance) from the period 1957–1980 in Denmark that had been freeze-dried upon collection. Growth competition assays revealed a significant negative correlation between the number of antibiotics to which an isolate was resistant and its fitness relative to fully susceptible isolates and a reference isolate (a penicillin-resistant S. aureus, phage type 80, collected in 1980). Isolates resistant to penicillin, methicillin, tetracycline, and streptomycin showed a relative fitness of 96%; those also resistant to erythromycin, a relative fitness of 92%.
  
To further evaluate the effect of bacterial fitness on the prevalence of resistant strains, the authors used a mathematical model that accounted for antibiotic selective pressure. The model predicted a decline of strains with <96% relative fitness if 6% of the population consumes antibiotics, and a greater decline — even in strains with 99% relative fitness — if 3% of the population uses antibiotics.
  
Comment: These findings suggest that reduced fitness of multidrug-resistant S. aureus, together with decreased antibiotic use, is sufficient to explain the disappearance of these strains in Denmark — and perhaps the decline in MRSA rates currently seen in several countries (JW Infect Dis Jul 3 2012). Other factors such as improved hospital hygiene may also play a role, but their relative effect was not estimated.
Thomas Glück, MD Published in Journal Watch Infectious Diseases July 11, 2012
  
Citation(s): Nielsen KL et al. Fitness cost: A bacteriological explanation for the demise of the first international methicillin-resistant Staphylococcus aureus epidemic. J Antimicrob Chemother 2012 Jun; 67:1325.
http://www.ncbi.nlm.nih.gov/pubmed/22378682?dopt=Abstract

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