|
|
Dr.
B. Srinivas Kakkilaya, MD
Antimicrobials are considered as the greatest discovery of the twentieth
century. In the pre-antibiotic era, infectious diseases accounted for
significant morbidity and mortality and invasive medical procedures were fraught
with the risk of infection.
All this changed with the use of antimicrobial agents. But the miracle seems to
be short lived. Irresponsible and erratic use of these life-saving instruments
has resulted in the development of drug resistance in many organisms and deaths due
to hospital-acquired infections is on the rise. It appears that our complacency
is leading us into bigger problems in the millennium that has just dawned.
The first antimicrobials were
discovered in the mid-20's and many new molecules were discovered between 1960
and 1980. This 'golden era of antibiotics' saw a dramatic fall in the mortality
from infections. Since the 80's, not many new class of molecules have been
discovered and the funding into antimicrobial research is on the decline and now
deaths due to resistant infections is slowly increasing; in the U.S., mortality
due to nosocomial infections is now 4 times that due to road traffic
accidents.
Antibiotics are Life Saving drugs..
As all infections are potential
threats to life, antibiotics are life-saving instruments,
comparable to mechanical ventilation, dialysis and other advanced
life-support devices. They are largely responsible for improved
quality of life and increased life expectancy. Being
weapons of such importance, they should be used with all the care and
caution.
Why do doctors over-prescribe
antibiotics?
70-80% of prescriptions for antimicrobials are probably
written unnecessarily
"Antibiotics have been given for everything from headaches to ingrown
toenails; they are swallowed, sucked, injected and smeared; they are painted on
cuts, dumped into wounds, fed to the chickens and pigs and spread on the floors
of the hospital wards."
-Dr. Richard Novick
The following are the reasons:
-
Lack of confidence: While it is very easy to scribble a prescription, it
takes a fair amount of courage to avoid unnecessary prescriptions. Inability to
make a fairly accurate clinical diagnosis is one of the most common causes for
over-drugging. Inability to convince the patient about the nature and simplicity
of the illness and about the non-requirement of antibacterials is another
reason. Some doctors may harbour a notion that it is better to give
"something powerful" for every patient so as to achieve
"dramatic" results (Shot Gun therapy). But the fact remains that most
patients do not demand any particular prescription from their doctor and many
are indeed happy if they are explained about their problem and prescribed as
less drugs as possible. Fear of law-suits for 'negligence' ('act of omission') and hence 'defensive'
practice may also be another reason.
-
Peer pressure: Some doctors may have a fear that if they do not
prescribe, their 'next door' colleague may prescribe these 'powerful' drugs and
get all the credit for 'curing' the patient. To avoid this 'loss of practice'
they tend to prescribe these 'powerful' remedies. This is another face of
'defensive' practice.
-
Patient pressure : Rarely, however, one may come across patients, some of
them with half-knowledge, who insist on a prescription for antibacterials so as
to "get better at the earliest" (because they are "very busy and
have no time to lie down in bed") or to "avoid any hassles",
particularly in cases of children and the elderly. Although in such situations it is the
duty of the doctor to resist any such pressures, some doctors may yield to
these pressures, often to appease the patients and to 'save' their practice.
-
Company pressure: With hundreds of pharmaceutical companies and
thousands of medical representatives, it is natural to come under some pressure
for prescribing these drugs, which earn handsome profits for the drug industry.
("Volume building products, Sir", the representative would tell us). With
competition hotting up, the companies seem to mislead the doctors about the
indications, suppress the facts on adverse effects and hide the facts on cost of
therapy. Recently there is a dangerous trend of 'combining' antibacterials and
marketing them for imaginary diseases. Many of the so called 'newer' antibiotics
(which are in fact nothing more than modifications of existing molecules) are
priced exorbitantly (even hundred times more than their older congeners) without
offering any benefits over the older, time tested drugs. But it has become
rather fashionable to prescribe these drugs, with many doctors feeling that
'costlier must be better'.
The Three Most Common
Situations For Antibiotic Abuse
It has been observed that the three commonest reasons for prescribing
antibacterials are fever, sore throat and diarrhoea. In all these three
situations, antibiotics are most often prescribed unnecessarily. Viruses being
more abundant, these diseases are also most often due to the viral infections
and antibacterials have no role to play in their management. Use of
antibacterials in non-bacterial illness results only in the destruction of
susceptible bacteria and selective proliferation of resistant bacteria, thus
aiding the propagation of bacterial drug resistance.
Fever: It is a manifestation of hundreds of diseases, infective and
non-infective. Antibacterials DO NOT have any beneficial effects in cases of
fever due to non-bacterial causes. Self-limiting viral infections are the
commonest infectious causes for fever and antibacterials have no role to play in
their management, neither do they shorten the duration of the illness nor do
they "prevent secondary infections". Premature, presumptive and
indiscriminate use of antibacterials in all cases of fever adds to the cost of
therapy, adverse effects (ampicillin rash in infectious mononucleosis being a
classic example!), development of drug resistance and may mask the signs of
bacterial infection, making a proper diagnosis difficult. Therefore, the urge to
prescribe antibacterials in all cases of fever should be curbed. All attempts
should be made to localize the site and type of the infection. Empirical
antibacterial therapy should be reserved only for emergencies (see below).
High grades of 'fever' may be managed with antipyretics like paracetamol or mefenamic acid (and not NSAIDs
or their combinations, the 'wonder pills' for
'pain and fever'!) and it should never be forgotten that antimicrobials are
NOT antipyretics.
Sore throat: It is probably the commonest illness where antibacterials
are misused the most. Although it accounts for 13% of all office visits, it has
been found in various studies that only 8 to 20% of persons with a sore throat
make a visit to a general practitioner (and in the other 80-90% it cures
spontaneously!). Streptococcal sore throat is almost unknown in children below
the age of 2 years and uncommon below 4 years. Roughly 10 to 20% of persons who
present to an out-patient department will have group A Streptococci on throat
culture and the other 80 to 90% with a sore throat will have a negative throat
culture. But using clinical judgment alone will mean that 20 to 40% (or even
more) of this large group of persons will receive antibiotics. Randomized trials
designed to show the benefits of antibiotics over aspirin or acetaminophen in
adults with sore throat have shown either no difference or a modest benefit. In
most trials, the fever difference was one degree Celsius or less and it was not
determined if patients felt this as an important difference. A survey of
physicians in 17 European countries reported that fever in patients with
tonsillitis resolved itself in two or three days, with or without antibiotic
treatment. Therefore routine use of antibacterials in cases of sore throat is
often uncalled for.
The Sore Throat Score developed by a group of American emergency room
physicians for the clinical diagnosis of Group A Streptococcal (GAS) pharyngitis
in adults can be useful in making a clinical diagnosis of Streptococcal
infection (particularly in adults) and may help in decisions about antibacterial
use. It includes the following four signs: 1. Tonsillar exudate 2. Swollen
anterior cervical nodes 3. A history of a fever of more than 380 C.
4. Lack of a cough.
|
The Sore Throat
Score for Group A Streptococcal (GAS) infection |
|
Score |
Chance of GAS |
% of patients |
Treatment |
|
None |
2.5% |
15% |
Only symptomatic |
|
One |
6-7% |
30% |
,, |
|
Two |
14-17% |
25% |
Throat swab; antibiotics after report |
|
Three |
30-34% |
20% |
,, |
|
Four |
56% |
10% |
Throat swab and antibiotics |
If the score is one or less (about 45% of patients and chance of GAS less
than 10%), only symptomatic treatment is indicated. For scores 2 and 3 (45% of
patients, and chance of GAS 14-34%), a throat swab culture should be taken and
only symptomatic treatment should be prescribed until the culture report is
available. Antibiotics should be prescribed only if the culture shows a
bacterial infection. If the score is four (only 10% of patients and chance of
GAS 56%), a throat swab culture should be obtained and antibiotics can be
started if the situation demands. By following this simple method, 70-80% of
antibacterial prescriptions for sore throat can be avoided, saving crores of
rupees every year.
Diarrhoea: It is another condition where antibacterials are often
over-prescribed. While there are many causes for diarrhoea, infective and
non-infective, the fact remains that most of them are self-limiting and require
only adequate rehydration. In all doubtful cases, a stool examination should be
done for ova, cyst, blood and hanging drop if cholera is suspected. Stool
culture can be done in the presence of severe and/or bloody diarrhoea, fever and
systemic toxicity. Presence of polymorphonuclear leukocytes on Wright’s or
Methylene blue staining usually suggests infection with Salmonella, Shigella,
invasive E. coli, Yersinia, or E. histolytica. Indications for antimicrobial
therapy in diarrhoeal diseases would include patients with high fever, bloody
diarrhoea, severe dehydration, systemic toxicity, extremes of age, malignancy,
immunocompromise, abnormal heart valve, vascular or cardiac prosthesis and
hemolytic anemia, history of recent antibiotic use, recent travel, outbreak of food poisoning in the community and in patients
suffering from Shigellosis, cholera, traveler's diarrhoea, parasitic diarrhoeas
and pseudomembranous enterocolitis.
The recent trend of the drug companies
marketing combinations of quinolones and nitroimidazoles (like tinidazole) for
"mixed diarrhoeas" should not only be discouraged, but also opposed.
The 'Combined Antibacterial'
Wonder Pills From India!
|
Combination |
Number of brands available |
|
Ciprofloxacin + Tinidazole |
37 brands |
|
Nalidixic acid + Metronidazole |
13 brands |
|
Norfloxacin + Metronidazole |
6 brands |
|
Ofloxacin + Tinidazole |
2 brands |
|
Furozolidone + Metronidazole |
14 brands |
"Mixed infections" with bacteria and amoeba are never known to
occur and this 'mixing' is done by the drug industry to sell two drugs for
indications where none may be needed. It is a matter of shame for all of us if
the claims of the drug industry that these 'combined, easy-for-the-doctor pills'
(now totaling more than 70 brands!) have a market share of nearly Rs.200 crore
should be true.
Rational Use of Antibiotics
Antibiotics are the most important weapons in our hands. Each
one of them have been invented after spending considerable amount of time,
energy and money. Therefore, we cannot afford to lose them. We must exercise considerable restraint in prescribing
antibacterials and restrict the use of antibacterials to only certain definite
indications.
Indications for antibacterial therapy:
-
Definitive therapy:
This is for proven
bacterial infections. Antibiotics (read antibacterials) are drugs to tackle
bacteria and hence should be restricted for the treatment of bacterial
infections only. This may sound silly, but most doctors seem to forget this
simple fact! Attempts should be
made to confirm the bacterial infection by means of staining of
secretions/fluids/exudates, culture and sensitivity, serological tests and
other tests. Based on the reports, a narrow spectrum, least toxic,
easy-to-administer and cheap drug should be prescribed.
Empirical therapy: Empirical antibacterial therapy
should be restricted to critical cases, when time is inadequate for
identification and isolation of the bacteria and reasonably strong doubt of
bacterial infection exists: septicemic shock/ sepsis syndrome,
immunocompromised patients with severe systemic infection, hectic temperature,
neutrophilic leukocytosis, raised ESR etc. In such situations, drugs that
cover the most probable infective agent/s should be used.
Prophylactic therapy: Antimicrobial prophylaxis is administered to susceptible
patients to prevent specific infections that can cause definite
detrimental effect. These include antitubercular prophylaxis, anti rheumatic
prophylaxis, anti endocarditis prophylaxis and prophylactic use of
antimicrobials in invasive medical procedures etc. In all these situations, only
narrow spectrum and specific drugs are used. It should be remembered that
there is NO single prophylaxis to 'prevent all' possible bacterial infections.
What antibacterial?
There are more than 100 antibacterials available today, and each one has its
own spectrum of activity, adverse effect profile and cost. The doctor should
consider many factors before prescribing an antibacterial agent so as to make
the treatment most effective with least adverse effects and cost.
The following factors should be considered while prescribing an antibacterial
agent:
Site of infection:
As a Rule Of The Thumb, it can be remembered that the infections above
the diaphragm are caused by Cocci and Gram positive organisms and infections
below the diaphragm are caused by Bacilli and Gram negative organisms, although
there are exceptions.
Examples:
Infections above the diaphragm: Upper respiratory tract infections like
pharyngitis, tonsillitis, sinusitis, otitis, epiglottitis etc. are commonly caused by
organisms like Streptococcus pyogenes, S. pneumoniae, Fusobacteria,
Peptostreptococci (rarely Mycoplasma, H. influenzae) etc. and can be treated with
drugs like Penicillins, Cephalosporins and Macrolides. Lower respiratory tract
infections like bronchitis, pneumonitis, pneumonia, lung abscess etc. are
generally caused by the organisms Streptococcus pyogenes, S. pneumoniae,
Fusobacteria, Peptostreptococci, Staphylococcus aureus (rarely Mycoplasma, H.
influenzae, Moraxella, Klebsiella) etc. and can be also managed with
Penicillins, Cephalosporins, Macrolides and Tetracyclines.
Infections below the diaphragm: Examples include urinary tract infection, intra-abdominal
sepsis, pelvic infections etc. and these are caused by the organisms like E.
coli, Klebsiella, Proteus, Pseudomonas, Bacteroides etc. Quinolones,
Aminoglycosides, 3rd generation cephalosporins
and Metronidazole, alone or in combination are useful in these infections.
There are certain sites where the infection tends to be difficult for
treatment: meningitis (impenetrable blood-brain barrier), chronic prostatitis
(non-fenestrated capillaries), intra-ocular infections (non-fenestrated
capillaries), abscesses (thick wall, acidic pH, hydrolyzing enzymes etc.),
cardiac and intra-vascular vegetations (poor reach and penetration),
osteomyelitis (avascular sequestrum) etc. In such cases higher dose, more
frequent administration, longer duration, antibacterial combinations and
lipophilic antibacterials may have to be used.
Type of infection: Infections can be localised or extensive; mild or
severe; superficial or deep seated; acute, sub acute or chronic and
extracellular or intracellular. For extensive, severe, deep seated, chronic and
intracellular infections, higher and more frequent dose, longer duration of
therapy, combinations, lipophilic drugs may have to be used.
Severe infections (bacteremia / pyemia / sepsis syndrome / septic shock;
abscesses in lung/ brain/ liver/ pelvis/ intra-abdominal; meningitis/
endocarditis/ pneumonias/ pyelonephritis/ puerperal sepsis; severe soft tissue
infections / gangrene and hospital acquired infections) can be life threatening
and rapidly fatal. In such situations the drug absorption, distribution and
excretion could be altered due to tissue hypoxia, changes in hemodynamics, renal
and hepatic perfusion, GI absorption etc. The drug dynamics can also be altered
due to acidosis, altered permeability, presence of hydrolysing enzymes at the
site of infection etc. Also in such situations, possibility of infection with
multiple organisms and of drug resistance make the choice difficult. In all such
situations therefore, attempts should be made to identify and isolate the
infecting organism from the site as well as blood by staining (of infected
specimen and buffy coat smear) and culture (of infected specimen and two
specimens of blood). In treating the severe infections, drugs should be
administered by only intravenous route to ensure adequate blood levels. Only
bactericidal drugs should be used to ensure faster clearance of the infection.
If the site of infection is known, narrow spectrum drugs should be used. If the
site is unknown, attempt should be made to cover all possible organisms,
including drug resistant Staphylococcus, Pseudomonas and anaerobes. A
combination of penicillins/3rd generation cephalosporins,
aminoglycosides and metronidazole may be used. The dose should be higher and
more frequent. Whenever possible, a switch to oral therapy should be made.
Isolate and sensitivity: Ideal management of any significant bacterial
infection requires culture and sensitivity study of the specimen. If the
situation permits, antibacterials can be started only after the sensitivity
report is available. Narrow spectrum, least toxic, easy to administer and
cheapest of the effective drugs should be chosen. If the patient is responding
to the drug that has already been started, it should not be changed even if the
in vitro report suggests otherwise.
Source of infection: Community acquired infections are less likely to be
resistant whereas hospital acquired infections are likely to be resistant and
more difficult to treat (e.g. Pseudomonas, MRSA etc.).
Host factors: Age of the patient, immune status, pregnancy and lactation,
associated conditions like renal failure, hepatic failure, epilepsy etc. should
be considered in choosing the antibacterial agent.
Age:
Infants: Chloramphenicol (can cause grey baby syndrome) and sulfa (can cause kernicterus)
are contraindicated.
Below the age of 8 years: Tetracyclines are contraindicated because they are known to discolour the teeth.
Below the age of 18 years: All fluoroquinolones are contraindicated because they are known to
cause arthropathy by damaging the growing cartilage.
Elderly: In the
elderly, achlorhydria may affect absorption of antibacterial agents. Drug elimination is
slower, requiring dose adjustments. Ototoxicity of aminoglycosides may be
increased in the aged.
Compromised immune status:
In patients with extremes of age, HIV infection, diabetes mellitus, neutropenia, splenectomy,
using corticosteroids or immunosuppressants, patients with cancers / blood
dyscrasias, ONLY bactericidal drugs should be used. And it is indeed debatable
whether antibacterials should be used to treat infections like aspiration
pneumonia, UTI, catheter infections, infections through life support systems,
pressure sores etc. in patients who are terminally ill (brain dead, patients
with massive stroke, terminal cancers, advanced age, terminal AIDS etc.).
Pregnancy:
Drugs with known toxicity or un-established safety like tetracyclines,
quinolones, streptomycin, erythromycin estolate and clarithromycin are
contraindicated in all trimesters and sulfa, nitrofurantoin and chloramphenicol
are contraindicated in the last trimester. Drugs with limited data on safety
like aminoglycosides, azithromycin, clindamycin, vancomycin, metronidazole,
trimethoprim, rifampicin and pyrazinamide should be used with caution when
benefits overweigh the risks. Penicillins, cephalosporins, INH and ethambutol
are safe in pregnancy. In lactating mothers sulfa, tetracyclines, metronidazole,
nitrofurantoin and quinolones are contraindicated.
Renal failure:
Tetracyclines are absolutely contraindicated; aminoglycosides,
cephalosporins, fluoroquinolones and sulfa are relatively contraindicated; and
penicillins, macrolides, vancomycin, metronidazole, INH, ethambutol and
rifampicin are relatively safe. It is better to avoid combinations of
cephalosporins and aminoglycosides in these patients because both these classes
of drugs can cause nephrotoxicity.
Hepatic failure:
No
drugs are absolutely contraindicated; chloramphenicol, erythromycin estolate,
fluoroquinolones, pyrazinamide, rifampicin, INH and metronidazole are relatively
contraindicated and penicillins, cephalosporins, ethambutol and aminoglycosides
are safe.
Drug factors (see):
1. Hypersensitivity: If the patient has
prior history of hypersensitivity the concerned antibacterial agent should be
avoided. It is therefore important to elicit this history in all patients.
2.
Adverse reactions: Certain adverse reactions warrant discontinuation of therapy
and the doctor should adequately educate the patients on these adverse effects.
3. Interactions: Interactions with food and other concomitant drugs should be
considered before instituting antibacterial therapy so as to maximize efficacy
and minimize toxicity.
4. Cost: Lastly, but not the least, the cost of therapy should be considered
in choosing the antibacterial agent and in a developing country like India with
limited spending on healthcare, this does assume significance. It should always
be remembered that just because a particular drug is expensive, it need not be
superior than the cheaper ones. For example, cheaper drugs like doxycycline or
co-trimoxazole would be as effective as the costlier clarithromycin or
cephalosporins in the management of LRTI.
Choice
of
Antibiotics
|
Site of infection |
Type of infection |
Drugs of choice |
Duration of treatment |
|
Upper respiratory tract infection |
Throat infections |
Erythromycin or amoxycillin or
penicillin V |
10 days for Group A Streptococcal infections, 10-14 days for mycoplasma. |
|
Sinusitis |
Amoxycillin or doxycycline or erythromycin |
2 weeks |
|
Otitis media |
Amoxycillin or erythromycin |
7 days |
|
Lower respiratory tract infection |
Bronchitis |
Amoxycillin or co-trimoxazole or tetracycline |
7 days |
|
Uncomplicated pneumonia |
Amoxycillin or benzyl penicillin or erythromycin |
7 days |
|
Severe pneumonia of unknown aetiology |
Erythromycin plus cefuroxime or cefotaxime |
7-10 days |
|
Suspected atypical pneumonia |
Erythromycin |
10-14 days |
|
Hospital acquired pneumonia |
Cefotaxime or ceftazidime or an antipseudomonal penicillin plus an
aminoglycoside |
7-10 days |
|
Urinary tract infection |
Lower urinary tract infection |
Fluoroquinolone or Co-trimoxazole or amoxycillin or nitrofurantoin |
3-7 days |
|
Upper urinary tract infection, pyelonephritis or prostatitis |
Fluoroquinolones or co-trimoxazole or gentamicin or cephalosporins |
10-28 days |
|
Pelvic inflammatory disease |
Doxycycline plus metronidazole |
Metronidazole for 7-14 days and doxycycline for 14-21 days |
|
Skin infections |
Impetigo |
Topical fusidic acid or mupirocin; erythromycin if wide spread |
7-10 days |
|
Cellulitis |
Amoxycillin plus cloxacillin or erythromycin or co-amoxyclav |
7-10 days |
|
Surgical |
Clean (cardiac, vascular, neurologic or orthopaedic) |
Cefazolin |
Before and during procedure |
|
Clean-contaminated (head and neck, high-risk gastroduodenal or biliary
tract surgery; caesarian section; hysterectomy) |
Cefazolin |
Before and during procedure |
|
Clean-contaminated (colorectal surgery or appendicectomy) |
Cefoxitin or 3rd gen. Cephalosporins plus metronidazole |
Before and during procedure |
|
Dirty (ruptured viscus) |
Cefoxitin plus gentamicin or 3rd gen. Cephalosporins plus
metronidazole |
Before and 3-5 days after procedure |
|
Dirty (traumatic wound) |
Cefazolin |
Before and for 3-5 days after trauma |
Antimicrobial agents for common use
|
Drug |
Route of administration |
Dose and frequency of administration |
Contra indications/ caution |
Interactions |
Adverse effects |
|
Penicillin G |
Intramuscular, Intravenous |
10-20 L Units every 2 to 6 hrs. |
Hypersensitivity |
None significant |
Hypersensitivity- rashes, anaphylaxis, fever, joint
pains, angioedema, serum sickness like reaction, blood disorders, C.N.S.
toxicity in high doses; colitis and diarrhoea; ampicillin rashes are more
common in infectious mononucleosis, chronic lymphatic leukemia and HIV
infection. |
|
Penicillin V |
Oral |
400-800 mg every 6-8 hours |
|
Ampicillin |
Oral, intravenous |
New born (<1 wk): 25-50 mg/kg 12 hrly 1-4 wks: 100-200
mg/kg/day 8th hrly Older children: Same dose 6 hourly Adults:
1-12 g/day, 6 hourly |
|
Amoxycillin |
Oral, intravenous |
Oral: 250 mg-1g every 8 hourly; Severe RTI: 3 g 12 hourly
Intravenous: 500 mg -1 g every 6-8 hrs., Children-
50-100
mg/kg in 3-4 doses. |
|
Cephalexin
(1st gen.) |
Oral |
250mg-1 g every 6 hours |
Hypersensitivity, renal failure, porphyria |
Hypersensitivity rashes, joint pains, rarely
anaphylaxis; abdominal discomfort; colitis; erythema multiforme;
reversible interstitial nephritis; transient hepatitis; blood disorders;
dizziness etc. |
|
Cefazolin
(1st gen.)
|
Intravenous |
1-1.5 g every 6 hours |
|
Cefadroxil |
Oral |
1 g every 12 hours |
|
Cefuroxime
(2nd gen) |
Intravenous, oral (axetil) |
Up to 3 g every 8 hours i.v.
250-500 mg 12 hourly oral
|
|
Cefotaxime
(3rd gen.) |
Intravenous |
1-2 g every 4-8 hours |
|
Ceftriaxone
(3rd gen.) |
Intravenous |
1-2 g every 12-24 hours |
|
Ceftazidime
(3rd gen., anti pseudomonal) |
Intravenous |
1-2 g every 8 hours |
|
Cefoperazone
(3rd gen., anti pseudomonal)
|
Intravenous |
1.5 to 4 g, 6-8 hrly |
|
Gentamicin |
Intramuscular, intravenous |
Adults: 2 mg/kg loading dose, then 3-5 mg/kg per day,
every 8 hours
Age < 2 yrs: 2-2.5 mg/kg every 8 hrs. |
Renal failure; myasthenia gravis; |
Ototoxicity may worsen with potentially ototoxic diuretics like
furescemide |
Ototoxicity, nephrotoxicity, more common in the elderly
and in renal failure; may impair neuromuscular transmission and may cause
transient myasthenia |
|
Amikacin |
Intramuscular, intravenous |
15 mg/kg/day in 2-3 equally divided doses |
|
Tetracycline |
Oral |
Adults: 1-2 g/day in 2-4 doses.
Children >8 years:
25-50 mg/kg/day in 2-4 doses |
Pregnancy, lactation; renal impairment; children below 8
years; SLE |
Antacids reduce absorption; anticonvulsants increase metabolism of
doxycycline, calcium salts, oral iron and zinc reduce absorption;
sucralfate and bismuth salts reduce absorption. |
Nausea, vomiting diarrhoea; erythema (discontinue);
benign intracranial hypertension; colitis |
|
Demeclocycline |
Oral |
150 mg 6 hourly or 300 mg 12 hourly in adults |
|
Doxycycline |
Oral |
100 mg twice daily on the first day, then 100 mg once or
twice a day depending on the severity of infection |
|
Erythromycin |
Oral |
>8 years: 250-500 mg every 6 hours or 0.5-1 g every
12 hrs
2-8 years: 250 mg every 6 hours
< 2years: 125 mg every 6 hours |
Hepatic and renal impairment; prolonged QT interval;
porphyria; estolate in liver disease |
Avoid use with astemizole, terfenadine, pimozide, midazolam, zopiclone,
cisapride; increases theophylline levels |
Nausea, vomiting, abdominal discomfort; diarrhoea;
rashes; arrhythmias; cholestatic jaundice |
|
Norfloxacin |
Oral |
400 mg twice daily for 3-7 days for UTI |
Age less than 18 years; pregnancy and lactation;
epilepsy; hepatic and renal impairment |
Increased risk of convulsions with NSAIDs; antacids reduce absorption;
anticoagulant effects of coumarins enhanced; iron and zinc reduce
absorption; increases levels of theophylline, avoid concomitant use. |
Nausea, vomiting, diarrhoea, headache, dizziness, sleep
disorders, rash, pruritus, anaphylaxis, increase in urea, creatinine and
liver enzymes, arthralgia and myalgia, blood disorders, restlessness,
hallucinations, depression, tendon damage |
|
Ciprofloxacin |
Oral,
intravenous |
Oral: UTI: 250-500 mg twice daily
LRTI: 500-750 mg twice a day
Intravenous: 200-400 mg over 30-60 minutes, twice a day |
|
Co-trimoxazole |
Oral |
Adult: 960-1.44 g twice daily; 480 mg twice daily if
used for >14 days.
Children:120-480 mg 12 hourly |
Hepatic and renal impairment; blood disorders; G6PD
deficiency; breast feeding |
Enhanced effects of warfarin, sulfonylureas, phenytoin |
Nausea, vomiting, rash, Steven Johnson syndrome
(discontinue), blood disorders (discontinue), glossitis, arthralgia, liver
damage, colitis, eosinophilia, tinnitus, interstitial nephritis |
|
Metronidazole |
Oral, intravenous |
800 mg initially, then 400 mg 8 hrly; Intravenous: 500
mg 8 hrly.
Children: 7.5 mg/kg 8 hourly |
Hepatic failure, pregnancy and lactation, |
Disulfiram like reaction with alcohol; enhances effect of
anticoagulants, phenytoin; increases toxicity of lithium |
Nausea, unpleasant taste, furred tongue, headache,
drowsiness, anaphylaxis, rashes. |
|
Nitrofurantoin |
Oral |
50-100 mg every 6 hours |
Renal impairment; G6PD deficiency; full term pregnancy and lactation;
major organ failure |
Magnesium trisilicate retards absorption |
Anorexia, nausea, vomiting, acute and chronic pulmonary
reactions; SLE like syndrome; rashes etc. |
Methods of
administration of
antimicrobials
Route of administration: The route of administration depends on the site,
type and severity of the infection and the availability of a suitable drug.
Oral
route is the most preferred, easy and cheap, but it may not be reliable in all
circumstances, particularly in patients with severe infections, non-compliant
patients, in the presence of vomiting etc. Certain drugs like the
aminoglycosides and most 3rd generation cephalosporins are not available for
oral administration.
Intramuscular route should be generally restricted for the
administration of procaine and benzathine penicillin and single shot of
ceftriaxone; the absorption is not very reliable and it is painful and disliked
by the patients.
Intravenous route is the best for the management of severe
and deep-seated infections since it ensures adequate serum drug levels. Procaine penicillin
and benzathine penicillin should never be given I.V. However, some drugs are
not available for parenteral use (e.g. most macrolides, sulfa, tetracyclines).
Topical: Antibacterials are also
used topically, but drugs used for systemic administration should not be used in
skin ointments.
Dosage:
Dose depends on the age of the patient, weight of the patient,
associated conditions like pregnancy, renal and hepatic failure and site, type
and severity of infection. Generally the dose should be higher in cases of
severe, deep-seated infections and in pregnancy and lower in cases of renal
failure. While unnecessary overdosage only adds to the cost and
adverse effects, there should not be any compromise on adequate
dose.
See Dose
Frequency of administration: The drug should be administered 4-5 times the
plasma half-life to maintain adequate therapeutic concentrations in the serum
throughout the day. Frequency can be increased in cases of severe, deep seated
and sequestrated infections and reduced in cases of renal and hepatic failure.
Duration: Duration of therapy depends on the site, type and severity of
infection. (e.g. Tonsillitis-10 days; bronchitis-5-7 days; UTI-single shot to 21
days; lung abscess-2-8 weeks; tuberculosis-6-24 months etc.).
See Duration
Combinations: Judicious and
intelligent combination of different antibiotics can be very useful in treating
certain difficult infections and in preventing or overpowering resistance. On
the other hand irrational and unnecessary combinations can add to the cost and
adverse effects and help in the development of drug resistance.
Antibacterial combinations can be useful in the following
situations:
1. To sharpen the effect: Synergistic combination of two static drugs - e.g.
Combination of Trimethoprim and Sulfamethoxazole - Co-Trimoxazole
2. Treatment of infections with multiple organisms: Mixed
infections in lung abscess, peritonitis, soiled wounds etc., naturally require
multiple antibiotics for complete clearance of the infection - Penicillins (for
gram positive and certain anaerobes) + Aminoglycosides (for gram negative); metronidazole for bacteroides etc.
3. To prevent resistance: Use of combinations is a well known method
of preventing drug resistance. The classic example is the antitubercular therapy.
4. To overcome resistance: Combination of specific drugs can be useful
in overcoming the resistant infections. Examples include Penicillins + b
lactamase inhibitors/b
lactamase resistant penicillins for S. aureus; Penicillins/cephalosporins
+ aminoglycosides for Pseudomonas etc.
The following combinations are irrational, not useful or even harmful:
Combinations of bactericidal with bacteristatic drugs (e.g. Penicillins with
tetracyclines);
Combinations of drugs with similar toxicity (e.g. chloramphenicol and sulfa)
Combining drugs for non-existing ‘mixed infections’ (e.g. tablets of
ciprofloxacin
+ metronidazole/tinidazole).
Response to treatment:
It depends on the
nature and sensitivity of the agent,
specificity of the drug, bio-availability and dosage. Longer the doubling time
of the organism, longer the time it takes to respond. Thus a Streptococcal
pneumonia can respond within 24 -48 hours, but tuberculosis may take 2-8 weeks
to respond. One should have the
patience to wait for the adequate period before changing the drug (e.g. S. pneumoniae infections - 24-48 hours;
E. coli - 24-48 hours; S. typhi - 4-7 days;
M. tuberculosis - 2-8 weeks etc.). Drugs should be changed midway only when
there is absolutely no response or there is no expected response and the
sensitivity report also suggests resistance.
Resistance to Antimicrobial
Agents
Resistance to antimicrobial agents is one of the greatest problems faced by
the medical community. These powerful weapons, developed by spending millions of
dollars and years of dedicated research, have been rendered less effective or
totally ineffective only because of our own negligence and complacence. This is
indeed frustrating.
The following table provides on overview of
some of the recent examples of resistance to antimicrobials:
|
Organism |
Resistance |
|
Gram Positive cocci |
Methicillin resistant Staph. aureus and coagulase negative Staphylocci,
penicillin resistant Pneumococci, macrolide resistant Streptococci,
vancomycin resistant Enterococci. |
|
Gram negative cocci |
Penicillin, quinolone resistant gonococci. |
|
Gram negative bacilli |
Enterobacteriaccae resistant to B lactams and B lactamase inhibitors,
multi drug resistant pathogens include Shigella, E. Coli, Salmonella. |
|
Acid fast bacilli |
Multi drug resistant M. tuberculosis. |
Factors contributing to antimicrobial resistance:
Antimicrobial
resistance, initially a problem in hospitals and developing countries, today
affects the world at large. The reasons for resistance are many. The WHO reports
that the antimicrobial agents are used by too many people to treat the wrong
kind of infection in the wrong dosage and for the wrong period of time in both
industrialized and developing countries. Increase in poverty, over crowded
living areas, crowded day care centers have all contributed in spreading the
resistant bacterial infection. The tremendous increase in the size of the high
risk populations because of immunocompromise, the increased frequency of
invasive medical interventions and prolonged survival of patients with chronic
debilitating disease have amplified the problem.
Resistance to antimicrobial agents can be due to various mechanisms:
-
Inability of the drug to reach the organisms
-
Inactivation of the drug
-
Alteration in the target
Resistance may be acquired by mutation and passed onto the next generations.
It may also be acquired by horizontal transfer from a donor cell by
transformation, transduction or conjugation.
Control of use of antimicrobial agents: The following methods can be used
to control the use of antimicrobial agents in hospitals: Education programmes like staff conferences, lectures and
audiovisual programmes; availability of clinical pharmacist consultants; control
of contact between pharmaceutical representatives and staff physicians and of
various sponsorships from companies; restriction of hospital formulary to
minimum number of agents needed for most effective therapy; availability of
diagnostic microbiology laboratory sensitivity tests and appropriate selection
of sensitivity tests for organism and site; automatic stop orders for specific
high-cost agents and written justification for high-cost agents etc.
Further
Reading:
- McIsaac WJ, White D, Tannenbaum
D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients
with sore throat. Can Med Assoc J 1998;158(1) Full Text at
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1228750&blobtype=pdf
- Danchin MH, Curtis N, Nolan
TM, Carapetis JR. Treatment of sore throat in light of the Cochrane verdict:
is the jury still out? MJA 2002;177(9):512-515 Full text at
http://www.mja.com.au/public/issues/177_09_041102/dan10028_fm.html
- Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 1997, Issue 3. Art. No.: CD000023.
Available at http://www.cochrane.org/reviews/en/ab000023.html
- Linder JA, Bates DW, Lee GM, Finkelstein
JA. Antibiotic Treatment of Children With Sore Throat JAMA. 2005;294:2315-2322.
Full Text at http://jama.ama-assn.org/cgi/content/full/294/18/2315
- Bharathiraja R, Sridharan S, Chelliah LR, Suresh S, Senguttuvan M. Factors affecting antibiotic prescribing pattern in pediatric practice. Indian J Pediatr [serial online] 2005 [cited 2008 Apr 22];72:877-9. Available from:
http://www.ijppediatricsindia.org/text.asp?2005/72/10/877/17027
- De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for travellers' diarrhoea. Cochrane Database of Systematic Reviews 2000, Issue 3. Art. No.: CD002242.
Available at http://www.cochrane.org/reviews/en/ab002242.html
- Study shows excessive, inappropriate antibiotic
prescriptions for sore throats
Antibiotics needed in only 10 percent of adult sore throats
Available at
http://www.massgeneral.org/pubaffairs/releases/091101sorethroats.htm
- Prasad K, Kumar A, Singhal T, Gupta PK. Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD001832.
At http://www.cochrane.org/reviews/en/ab001832.html
- Lewis R. The Rise of Antibiotic-Resistant Infections Available at
http://www.fda.gov/Fdac/features/795_antibio.html
- Antimicrobial resistance. WHO Fact sheet N°194
(Revised January 2002) Available at
http://www.who.int/mediacentre/factsheets/fs194/en/
- Antibiotic / Antimicrobial Resistance. CDC Website At
http://198.246.98.21/drugresistance/index.htm
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