First, 3 interesting recent articles…

New England Journal of Medicine – July 12, 2018, pg 197-8

#I. “Oropharyngeal Tularemia from Freshly Pressed Grape Must”

A German winery hand picked one bunch of grapes and used amechanical harvester for another lot. The grapes lots wereseparately pressed

6 of 8 workers who tasted the mechanically harvested “freshmust” and none that only tasted the hand picked lot developedoral tularemia. High levels of F. tularensis was found in themechanically harvested wine, none in the other batch

Rodent DNA also found only in the mechanically harvested wine

Nothing beats a cool glass of freshly pressed Wine de Rodent!

.

.

Open Forum Infectious Diseases July 10, 2018 in print #2.“Microbiology Comment Nudge Improves Pneumonia Prescribing”

From Dept of Pharmacy services, Henry Ford Hospital , Detroit MI

210 patients on anti- MRSA or antipseudomonal antibiotics for respiratory infection were studied . Studies have shown vanco/pip-tazobactam account for 20% of antibiotics prescribed for CAP

Baseline 6 month period – non- pathogen containing sputum cultures were reported as “normal flora” only

Next 6 month study period negative sputum were now reported as “ normal flora only, No S. aureus/MRSA or P. aeruginosa”. Also educated providers about this new reporting result

After adjusting for severity etc., during the study period as compared to the baseline period, the new Lab comment was associated with a 5.7 fold increased odd of antibiotic de-escalation. Median 2 day decrease in broad spectrum coverage (stopping vanco or zosyn) as compared to baseline period

No mortality difference , significant decrease in acute kidney injury

.

.

BMJ June 27, 20183. “Risk of MRSA and C. difficle in patients with a documented PCN allergy: population matched cohort study”

Mass General Hospital, Boston MA What was risk of these 2 infections developing in

patients given non-Beta lactam antibiotics due to reported PCN allergy

5 to 16% of patients state they are PCN allergic. Studies by allergists however show 95% of these patients are actually not allergic- has resolved over time, side-effect and not allergy, viral exanthem with their illness, etc

Often lead to use of broad spectrum antibiotics leading to drug resistance and toxicities

In this large study ,alternative drugs associated with adjusted hazard ratio of 1.69 for MRSA and 1.26 for C. difficle

As expected, bad actors were macrolides, clindamycinand fluoroquinolones

Addressing “PCN allergies” may be important public health strategy

.

.

2018 Update on Fluoroquinolones- Use at your own risk ! Charles Krasner , M.D.

Sierra NV Veterans Affairs HospitalUniversity of NV, Reno School of MedicineJuly 19, 2018Antibiotic Stewardship Program -ECHO

.

.

.

.

2016 FDA Warnings: Potential fluoroquinolone side-effects

Increased risk, greater than with most other antibiotics, for causing C. difficile colitis

Acute Tendonitis- particularly Achilles tendonitis and rupture, can be unilateral or bilateral, and can occur at any time with these antibiotics

QT prolongation- can cause Torsades. Some fluoroquinolones have been taken off the market because of this problem.

Peripheral neuropathy- may be irreversible

Central nervous system toxicities- particularly in older patients

.

.

FDA Drug Safety Communication- FDA advises restricting use for certain uncomplicated infections. Posted May 12, 2016

FDA recommends that: Serious side effects associated with fluoroquinolone

antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections (UTI) who have other treatment options.

For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options.

Providers should instruct patients to contact their health care professional immediately if they experience any serious side effects while taking fluoroquinolone medicine such as tendon, joint and muscle pain; a “pins and needles” tingling or pricking sensation; confusion; and hallucinations.

Providers should stop systemic fluoroquinolone treatment immediately if a patient reports serious side effects, and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course.

.

.

July 2018 FDA adds additional fluoroquinolone warnings:

Fatal hypoglycemia Report of at least 67 cases of life-threatening

hypoglycemic coma- including 13 deaths, 9 with permanent and disabling injuries

Occurred more frequently in the elderly and those with diabetes taking an oral hypoglycemic medicine or insulin.

Others had renal insufficiency as a risk factor (? Was dose renally adjusted)

4 of these antibiotics have labeled drug interaction already with sulfonylurea

Seen mostly with levofloxacin (44), cipro (12)

.

.

Also, new neuropsychiatric side-effects noted in 2018 update-new labeling to make these warnings more prominent and consistent across all the fluoroquinolones

Disturbances Memory in attention impairment

(new) (new)

Delirium Nervousness(new)

Agitation Disorientation

.

.

Diagnosis of Uncomplicated Cystitis

Symptoms only: +dysuria, +frequency, no discharge or irritation:

***as much as 95% chance of cystitis *** Dipstick: leukocyte esterase + and/or nitrite + only 75%

sensitive, so symptoms more important for diagnosis even if dip is negative

Culture : 10⁵ (100,000) bacterial CFUs – traditional criterion for UTI- 50% sensitive – will miss up to half the cases of UTI- counts of 100 to 10,000 colonies – all at levels that may be called as “no growth” by micro lab. Least sensitive diagnostic test.

Thomas Hooton, M.D. UTI review NEJM 3/15/2012-don’t do dip stick, u/a or culture- can be negative or misleading- just treat on basis of classic symptoms in uncomplicated UTI

.

.

Why treat Acute cystitis?

*** Rarely progresses to severe disease even if untreated:

goal of treatment is to ameliorate symptomsIn selecting therapy, efficacy as well as “ecologic collateral

damage” (selecting for antibiotic resistant bacteria, causing C. difficile colitis ) should be considered equally- fluoroquinolones should be avoided, except in pyelonephritis

Avoid Quinolones and use First line agents whenever possible:Washoe County 2016 E. coli susceptibility:

98% Nitrofurantoin (Macrodantin) for 5 days75% Trimethoprim/sulfa (Bactrim) for 3 days approx. 90% cefdinir BID for 5 days

Fosfomycin for one dose (ciprofloxacin was only 78% susceptible)

.

.

Recent Study of antibiotic use in uncomplicated cystitis in 2 large private FP clinics with well insured patients

1546 visits –all women with any possible complicating factor were excluded- pregnancy, recurrent infection, antibiotic allergy, fever

Prescribed Antibiotics:52 % Fluoroquinolones- Cipro or levofloxacin (71 % of these

prescriptions were for 5 to 10 days of therapy, only 29% were for recommended 3 days)

36% nitrofurantoin (70% were for one week of therapy)12%- trimeth/sulfa (50% were for more than 5 days)

Conclusion- primary care physicians strongly prefer fluoroquinolones and prescribe longer courses of therapy than recommended in Guidelines

.

.

Clinical Inf Disease 2018 Kabbani et al. “Opportunities to improve Fluoroquinolone Prescribing in the U.S. for Adult Ambulatory Care Visits”

2014 National Ambulatory Medical Care Survey

31.5 million Fluoroquinolone Rx’s dispensed

7.9 million FQ rx (approx. 25% of total) given for either viral URI or bronchitis (conditions not requiring antibiotics) or not recommended for first line therapy ( uncomplicated UTI or sinusitis)

.

.

JAMA Internal Medicine – eprint Palms et. al. “Comparison of Antibiotic prescribing in Retail Clinics, Urgent Care Centers, Emergency Depts, and Traditional Ambulatory Care Settings in the U.S.”

CDC funded study of millions of patient visits and prescribing patterns prescription rates by care setting for visits for antibiotic inappropriate respiratory

diagnoses (viral URI, bronchitis, asthma, non-suppurative otitis media, etc)1. Urgent Care Center- 45.7%2. Emergency Dept- 24.6%3. Medical offices – 17.0%4. Retail clinics- 14.4%

Conclusion : “unnecessary prescribing practice in outpatient settings likely to exceed reported 30% of all dispensed antibiotics”

.

.

Guidelines for management of acute sinusitis

Antibiotics indicated for either symptoms for > 10 days, or severe symptoms with purulent nasal drainage and fever, or worsening symptoms after initial improvement

Empiric treatment suggestions:

1. Augmentin /high dose in adults

2. doxycycline if PCN allergic. Give 200mg initial loading dose to get effective blood levels

3. Levofloxacin only as alternative, No more than 5 days should be adequate.

Do not use azithromycin given high incidence of resistant strep pneumoniae

.

.

56 year old female with asymptomatic bacteruria

56 year old female has pre-op evaluation prior to elective hip replacement

Noted on urinalysis to have bacteriuria and positive culture but no symptoms

Surgeon prescribed one week of ciprofloxacin, completed day before surgery

Uneventful surgery, discharged

Readmitted next day with fulminant c.diff colitis and dies

.

.

77 year old male with “ penicillin allergy” and dog bite

4 days prior to ER visit bite in thenar aspect of hand when separating 2 dogs

Came to ER c/o progressive onset redness and swelling of hand and arm

Given oral levofloxacin 750mg daily for 5 days

One week later – develops severe unilateral Achilles tendonitis

.

.

What’s on line for patients to view

https://youtu.be/IMZoJAzNuUI

.

.

Bottom line

There is growing medical and public awareness that the fluoroquinolones are potentially toxic drugs. New serious toxicities are still being identified

Highest risk patients are elderly, on treatment for diabetes, have renal insufficiency , PPI use, hospitalized patients

The greatest overuse of these drugs are in treatment of uncomplicated UTIs and asymptomatic bacteriuria, both in using them in the first place and then prescribing them for a longer course than indicatedShould also not be first line treatment for sinusitis or acute bronchitis

Would be difficult to defend a fluoroquinolone Rx. in court if prescribed outside of guidelines and a serious complication develops

.

.