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NEWS FLASH |
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SWITCH THERAPY |
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GLOBAL ANTIBACTERIAL DRUGS IN THE
PIPELINE |
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AMAZING FACTS |
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HUMOR CORNER |
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NEWS FLASH |
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NEW INSIGHTS ON THE EMERGENCE
OF RESISTANCE IN THE COMMUNITY
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The worldwide
emergence of resistance has received a great deal of attention
and is causing considerable among both clinicians and
laypersons. Hospital based physicians have long been aware of
increasing resistance in microbial pathogens causing nosocomial
infections. For example of the staphylococcus aureus isolates
from bacteraemic patients in the intensive care unit are
resistant to methicillin. These MRSA strains typically are multi
- drug resistant and require vancomycin for therapy. The recent
41st Inter Science Conference on Antimicrobial Agents and
Chemotherapy (ICAAC 2002) meeting provides some new insights on
the emergence is resistance in the community and suggests that
complacency will not be justified in the near future.
Two types of MRSA
In 1999, the CDC reported 4 deaths from MRSA in health children
from Minnesota and North Dakota. These children had none of the
traditional risk factors for MRSA infection and clearly had
community acquired infections.
Dr.Fey and colleagues from the University of Minnesota,
presented at the ICAAC a new extremely important information on
community acquired MRSA (CA-MRSA) that differentiates from the
more common hospital acquired MRSA (HA-MRSA). CA-MRSA strains
produce super antigens (virulence factors of both Staphylococci
and Streptococci and is important because super antigen
production by these microbes in immunological-naive persons can
cause toxic shock syndrome). The HA-MRSA strains usually do not
produce super antigens.
This new
information can now be put in perspective for the practising
physician. There are 2 important types of MRSA infection: HA-MRSA
and CA-MRSA. HA-MRSA infections are nosocomial, usually involve
multi-drug resistant strains and are rarely associated with
toxic shock syndrome. The newer type of MRSA is CA-MRSA, which
involves strains that are resistant to beta-lactam agents and
may be associated with toxic-shock syndrome. |
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CIPROFLOXACIN REMAINS MOST
ACTIVE IN FIGHTING URINARY TRACT INFECTIONS
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"Ciprofloxacin is still highly active in vitro against UTI
causing pathogens even after 14 years of use." |
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This data was presented at the
Inter Science Conference on Antimicrobial Agents and
Chemotherapy (ICAAC) December. The study covering data
gathered from 33 centres in 14 European countries, is one of
the largest of its type carried out to date in Europe.
Urinary Tract Infections are
among the most common reasons for adults to seek medical
attention, and are among the most frequently occurring
infections arising in the hospital setting. Common UTIs
include cystitis (inflammation of the urinary bladder) and
prostatitis (inflammation of the prostate). Each year, UTIs
account for more than five to seven million physician office
visits, 20 percent of all prescriptions, and require or
complicate more than one million hospital admissions . UTIs
affect women more frequently than men; about 40 to 50
percent of women report experiencing at least one UTI in
their lifetime. Left untreated or improperly treated, some
UTIs can lead to pyelonephritis, an infection of the kidneys
that can require hospitalization. Frequently caused by a
bacterial infection, UTIs are usually treated with
antibiotics.
In the study, participating
medical centres collected 50 or more samples of bacteria
from each of four groups of patients : those with community
acquired UTIs without complications, hospital acquired UTIs,
pyelonephritis, or UTIs in the elderly. The resulting 5750
samples were identified by the type of bacteria, and a
standardized laboratory test assessed each sample's
susceptibility to ciprofloxacin and other antibiotics.
Unlike most such studies, all UTI bacterial samples were
included in the
analysis rather than a certain, pre-selection of specific
bacteria types. Therefore, susceptibility to various
antibiotics were available for analysis.
Overall, ciprofloxacin was the most active in vitro of the
oral antibiotics tested. |
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| Susceptibility
of UTI pathogens to various antibiotics |
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Escherichia coli was the most
frequently isolated pathogens, accounting for 58.7 percent of
the 5750 UTI samples. Ciprofloxacin and nitofurantoin were the
most active oral antimicrobials against E. coli, with 92.2
percent and 93 percent of samples, respectively, demonstrating
susceptibility, followed by amoxycillin clavulanate (81
percent), trimethoprim (76.3 percent). Of E. coli isolates and
of all isolates combined, 20 percent were resistant to
trimethoprim while 30 percent were resistant to
sulfamethoxa zole.
This comprehensive study of the susceptibility of UTI
pathogens from Europe to a wide variety of antimicrobials,
together with current and past surveillance studies in the
U.S. indicate that Ciprofloxacin continues to be highly active
against gram -negative bacteria that are commonly associated
with UTIs. This data would be useful in Indian scenario as
ciprofloxacin is still the most widely used antibacterial in
treating urinary tract infections.
Ciprofloxacin 86.9%
Cefuroxime 80.1%
Amoxycillin - clavulanate 76.5%
Nitrofurantoin 72.8%
Trimethoprim 71.5%
Tetracycline 57.8%
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| SWITCH
THERAPY |
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COST-EFFECTIVE PRESCRIBING OF
ANTIBIOTICS |
| Introduction |
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Antimicrobial therapy is a concern
for all physicians who treat bacterial infections. Intelligent
use of antibiotics minimizes the incidence of side effects and
applies pharmacokinetic principles to assure the best patient
care as well as the most cost effective treatment.
Economic necessity has altered prescribing habits and hospital
formularies all over the globe. Intravenous- to-oral switch
therapy is probably the most talked about topic in antimicrobial
therapy today. Use of oral antibiotic therapy for all but the
most severe infectious diseases and, in cases demanding a course
of intravenous therapy initially making a switch to oral agents
as quickly as possible is what switch therapy is all about.
Although economic pressures have hastened this change, it is a
simple and medically sound manoeuvre.
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| Switch therapy :
definitions |
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Replacing intravenous antibiotics with effective oral
antibiotics in the treatment of serious infections (community
acquired pneumonia, nosocomial pneumonia and urinary tract
disease) is known as "switch therapy". If the change is
accomplished with the same antibiotic as that administered
intravenously then the change is labeled "step down therapy". If
a different drug is used (i.e. as in switching from an I.V. 3rd
generation cephalosporin to oral erythromycin), the concept is
labeled as "sequential therapy".
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When should switch therapy be initiated? |
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Typically, infections have been
categorized into 3 distinct stages once antibacterial treatment
has been instituted. (figure 1) |
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Figure 1: The recovery phase of most
patients with infections involves three stages |
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For the first 24
to 72 hours, most patients do not show further deterioration.
During this period, I.V. treatment should not be changed, unless
there is marked deterioration. Thereafter, at the stage of
"early improvement", the patient's condition begins to stabilize
as he/she shows evidence of early progress: improvement in
symptoms, signs and laboratory abnormalities. Finally the
patient enters the stage of 'definite improvement' during which
there is great improvement in the clinical condition; for many,
hospitalization continues during this phase as I.V. therapy
persists. However, supporters of early switch therapy advocate a
step-down to oral treatment much earlier, that is, at the start
of the early improvement phase of recovery. At this time the
switch to oral therapy (Figure 2) can be successfully made
without jeopardizing the recovery process and the patient can be
discharged much earlier than in the conventional approach to
therapy. |
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Figure 2: Switch therapy approach to
treatment |
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| Benefits of
Switch therapy |
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Assuming equivalent clinical
efficacy, switching patients from I.V. to oral therapy has
numerous advantages, both to the patient in terms of increased
comfort and reduced risk of I.V. line-associated complications,
and to the hospital in terms of decreased costs (see table 1).
Hospital savings
occur both directly (reduced drug acquisition and administration
costs and fewer days in hospital) and indirectly (diminished
risk of complications),
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Table 1: Benefits of switch
therapy
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Patient benefits
Improved comfort and clinical outcome from: |
- More
rapid mobilisation
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Avoidance of pain/phlebitis associated with indwelling
intravenous I.V. catheter
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Reduced likelihood of catheter sepsis/bacteraemia
Hospital
Benefits
Reduced costs secondary to:
- Lower drug
acquisition costs
- Reduced in
pharmacy drug preparation
- No need for
I.V. delivery systems to administer antibacterials
- Shorter
hospital stays
- Reduction in
hospital infections (especially bacteraemia associated with
line sepsis)
- Decreased
nursing time associated with I.V. line care/I.V. drug
administration.
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| Factors that
influence antimicrobialswitch therapy |
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Several factors influence the choice
of antibiotics and the decision concerning if or when to switch
from intravenous to oral antibiotic.
These factors
include :
- Patient
influences
- Pathogen
characteristics
- Antibiotic
properties
Patient
factors that traditionally influence antibiotic decisions
include :
- Severity of
illness
- patient age
- Comorbid
medical illness
- Mental status
or vital sign abnormalities
- Organ
dysfunction
- Laboratory
abnormalities, such as white blood cell count, arterial blood
gas abnormalities
- Elevated
blood urea nitrogen levels
- Bacteraemia
and radiographic findings
Pathogen characteristics that have an impact on the route and
duration of antibiotic therapy include virulence and resistance
patterns, and whether the pathogen is intracellular or
extracellular. For. example a virulent and resistant S. aureus (MRSA),
acquired in a nursing home, usually necessitates a more
prolonged course of intravenous antibiotics as compared to
infections caused by the less virulent and more antibiotic
sensitive pathogen.
Antibiotic properties that allow initiation of switch therapy
include dosing schedule, bioavailability, patient tolerance and
cost -- all of which influence compliance. It is also important
that an oral agent with the appropriate antimicrobial spectrum
is available. An ideal oral antibiotic for switch therapy should
have the following characteristics:
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Table 2: An ideal oral
antibiotic for switch therapy
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- Antimicrobial
coverage identical to the intravenous agent
- Once or
twice- a- day dosing to improve compliance
- High level of
bioavailability
- No adverse
side effects
- Low
acquisition cost
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| Gatifloxacin - an
excellent candidate for switch therapy for patients with
Community Acquired Pneuminia (CAP) |
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CAP accounts for approximately 10
million physician visits and 500,000 hospitalizations in the
United States. With these large numbers, the ease of antibiotic
administration including possible intravenous to oral switch --
becomes a vital consideration. The Infectious Diseases Society
of America recommends use of a -- lactam antibiotic with a
macrolide or a respiratory-active fluoroquinolone alone for
treatment of hospitalized patients with CAP.
-lactam antibiotics have limited coverage of potential pathogens
because they are inactive against atypical pathogens. Third
generation cephalosporins are active against S. pneumoniae, but
in vitro resistance to these drugs have been reported. Whether
in vitro data have clinical relevance is not entirely clear;
however the potential for resistant may be of concern.
The newer
fluoroquinolones like gatifloxacin fulfills the criteria for
switch therapy. |
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| Favourable
characteristics of gatifloxacin for switch therapy |
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Antimicrobial activity
Gatifloxacin has a broad spectrum of activity, allowing use in a
variety of infections affecting the respiratory tract, urinary
tract, skin and soft tissue. Gatifloxacin is active against gram
positive cocci, including S. pneumoniae, the most common
pathogen in CAP. It also covers H. influenzae and the atypical
pathogens in respiratory infections.
Pharmacokinetic properties
- Gatifloxacin
is rapidly absorbed and reaches maximum concentrations in less
than 2 hours.
- Gatifloxacin
is about 96% bioavailable.
- Oral and
intravenous formulations of gatifloxacin has nearly
identical plasma concentration versus time profiles;
therefore, intravenous formulations of gatifloxacin may be
considered therapeutically interchangeable.
- Gatifloxacin
also penetrate tissues well (volume of distribution 2 L/kg)
often with higher concentrations in tissues than in serum.
Tolerability
In general, the respiratory active fluoroquinolones like
gatifloxacin have favourable side effect profile with treatment
related adverse events that are usually mild and reversible with
cessation of therapy. |
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| Clinical
experience of gatifloxacin in CAP |
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Figure 3: Ideally suited as a START therapy
in hospitalized patient
Ref. : J
Resp Dis 1993;20(Suppl):560-569 |
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Summary |
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In today's
economic climate, streamlining antibiotic therapy (moving
patients expeditiously from intravenous to oral antibiotics,
often within 2-4 days of admission) must be considered part of
the treatment strategy from the time of admission. In the
treatment of CAP, the newer fluoroquinolone gatifloxacin
fulfills the criteria for good candidate for switch therapy.
Gatifloxacin can be administered once/day, is available in both
intravenous and oral formulations, cover the most common
pathogens, and has proven effectiveness. |
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| References |
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Pharmacotherapy 2001; 21(1):35-59
- Drugs and
Therapy Perspectives 1997; 10(3): 10-13
- Annals of
Pharmacotherapy 1998; 32: S22-S26
- Hospital
Medicine; 1998: 13-24
-
Pharmacotherapy 2001; (7 Pt 2): 100S-104S
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GLOBAL ANTIBACTERIAL DRUGS IN THE
PIPELINE |
| A novel compound
for preventing ventilator associated pneumonia (VAP) |
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Iseganan is a
synthetic analog of a protegrin, an antimicrobial peptide that
has broad activity against cocci, rods and yeast. The compound
is inactivated in the proximal small bowel, making it an
intriguing agent for oral decontamination. Administration of the
drug topically, every 4 hours for up to 5 days, to the oral
cavity of orally intubated patients decreased the oral microbial
burden. There are no adverse effects noted. This compound is
thus an interesting candidate for oral decontamination as a
method for decreasing the incidence of VAP. A clinical endpoint
study will be of interest to determine if there is an important
clinical benefits. |
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| Faropenem : A new
carbapenem in development |
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Faropenem
daloxate is a carbapenem in development. It is an orally active
agent being investigated in community acquired infections.
Against a variety of beta-lactamase Enterobacteriaceae faropenem
displayed potent activity. High potency was also found against
the 3 major pathogens (S. pneumoniae, H. influenzae and M.
catarrhalis). |
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AMAZING FACTS |
| The Respiratory System |
- The
capillaries in the lungs have a total area as a tennis court.
- A person at
rest usually breathes betwee 12 and 15 times a minute.
- The highest
recorded "sneeze speed" is 165 km/hr.
- At rest, the
body takes in and breathes out about 10 litres of air each
minute.
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| HUMOR
CORNER |
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1. At an
international conference, an American, a British, and a Russian
were discussing the shortcomings of their diagnoses.
"I can't
stand it sometime. We treat people for cancer, and then they die
of AIDS."
"I know what you mean," said the British. "We treat them for
yellow fever, and it turns out they had malaria. Then, of
course, they die."
"That is not a problem in our country," said the Russian doctor.
"When we treat people for a disease, they die of that disease."
2. Sam and John were out cutting wood, and John cut his right
arm off. Sam wrapped the arm in a plastic bag and took it and
John to a surgeon. The surgeon said, "You're in luck! I'm an
expert at reattaching limbs! Come back in four hours. "So Sam
came back in four hours and the surgeon said, "I got done faster
than I expected to, John is down at the local pub." Sam went to
the pub and saw John throwing darts with his right arm.
A few weeks later, Sam and John were out again, and John cut his
leg off. Sam put the leg in a plastic bag and took it and John
back to the surgeon. The surgeon said, "Legs are a little
tougher -- come back in six hours." Sam returned in six hours
and the surgeon said, "I finished early- John's down at the
soccer field and there was John, kicking goals.
A few weeks later, John had a terrible accident and cut his head
off. Sam put the head in a plastic bag and took it and the rest
of John to the surgeon. The surgeon said," "Heads are really
tough. Come back in twelve hours." So Sam returned in twelve
hours and the surgeon said, "I am sorry, John died." Sam said,
"I understand heads are toughest. "The surgeon said, "Oh, no!
The surgery went fine! John suffocated in that plastic bag!"
3. A man goes to the doctor and says to the doctor:
"It hurts when I press here"
(pressing his side)
"And when I press here" (pressing the other side)
"And here" (his leg)
"And here, here and here" (his other leg, and both arms)
So the doctor examined him all over and finally discovered what
was wrong ...
" You have
got a broken finger
4. A man finally
invested in a hearing aid after becoming virtually deaf. It was
one of those invisible hearing aids.
"Well, how do you like your new hearing aid?" asked his doctor.
"I like it great. I've heard sounds in the last few weeks that I
didn't know existed."
"Well, how does your family like your hearing aid?"
"Oh, nobody in my family knows I have it yet. Am I having a
great time! I've changed my will three times in the last two
months." |
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