Indian ft. Pediat. $9: 246, 1972

FOR GENERAL PRACTITIONERS:

ANTIBIOTICS IN PEDIATRIC PRACTICE*

ME~RBAS SINOH

New Delhi

Antibiotics are among the most widely misused drugs. They are often

used without any definite indication. I f a child develops fever, irrespective of cause, an antibiotic is prescribed as if it was an antlpyretic. It is a common observation these days to see a child with viral upper respiratory catarrh receiving

erythromycin; a child with measles being given tetracycline to prevent secondary bacterial infection; an infant with viral pneumonitis receiving chloramphenicol; and a patient with pyrexia of undeter- mined cause receiving a cocktail of

antibiotics and so on. Unfortunately, when the use of an antibiotic is indi- cated, many times a wrong agent is

prescribed or administered in a subopti- mal dose. Moreover, there is need for constant periodic re-evaluation for the choice of antibiotics in different clinical situations. As fast as manufacturers produce newer antibiotics against resis- tant bacteria, bacteria breed still newer strains to resist them. The chemotherapy o f tuberculosis and antibiotics for various viral, fungal and parasitic infections are not being discussed in this communica- tion.

The Choice o f Antibiot ics The choice is often influenced by

local fashion, advertising pressure, financial and emotional interest in a

*From the Department of Pediatrics, All-India Institute of Medical Sciences, New Delhi-16.

particular drug and perhaps even worse

by "clinical impressions". The following factors should be considered in selecting an antibacterial agent:

1. Age of the patient.

9. Nature of symptomatology, site and severity of infection.

3. Effectiveness of the agent against the suspected pathogen.

4. Availability. 5. Toxicity. 6. Cost. 7. Ease of administration.

8. Stability of the agent.

Survey o f C o m m o n l y Used and S o m e N e w e r Ant lmlcrobla l Agents

Sulfonamides

Many strains of gonococci, menin- gococci, shigella and coliform organisms

have become resistant to sulfas. Sulfa- t r iad and sulfi-soxazole (gantr is in)are safest while long acting sulfas should be avoided because of their increased toxicity. They should not be used in the neonate due to their ability to dislodge bilirubin from albumin binding sites. Sulfonamides are the drug of

choice in acute urinary tract infections and may be used for prophylaxis of rheumatic fever i f the patient is sensitive to penicillin or for economical reasons. They may also be used as an adjunct in the treatment of brucella and toxoplas-

mosis.

5 I N O H ~ A N T I B I O T I C S IN PEDIATRIC PRACTICE 247

2. Benzyl penicillin This is the drug of choice for in-

fections caused by streptococcus haemoly- ticus, pneumococci, gonococci, spiro- chaetes, diphtheria bacilli, Clostridia tetani, anthrax bacilli and non penicil- linase producing staphylococci. It is a very effective and safe antibiotic and can be administered orally as phenoxy methyl penicillin (penicillin V). Penicil- lin sensitivity may occur in 1%-2% children after parenteral use while reactions to oral penicillin are rare. When using massive doses, it should be remembered that 1.5 mEq of K or Na is contained in every I0,00,000 units of benzyl penicillin.

3. Erythromycin It has become fashionable to use

,erythromycin these days although its antibacterial spectrum is similar to penicillin and rather it is less effective, being bacteriostatic, it is safe but organisms develop resistance very fast. Its use is indicated in a patient allergic to penicillin and for the treatment of infections caused by penicillin resistant staphylococci.

ft. Tetracydines They are very widely used but are

toxic and relatively ineffective antibio- tics. Many organisms including group A beta haemolytic streptococci, entero- cocci and gram negative bacilli have become resistant to them. Tetracyclines become deposited in the enamel and bone causing disfiguration of the teeth and growth retardation. Their oral absorp- "don is very erratic and unpredictable. They frequently produce gastro-intestinal upsets and anorexia with alteration of ~he bacterial flora and superinfection

with staphylococci and Candida albicans. They occasionally produce fatty infiltration of the liver, pseudo- tumour cerebri, photosensitivity and renal tubular defects. Their use should be avoided below the age of 6 years. The definite clinical indications of tetracyclines include rickettsial infec- tions, psittacosis, lymphogranuloma venereum, primary atypical pneumonia, brucella and listeria monocytogenese meningitis in the newborn.

5. Chlor amphenicol Most gram positive and negative

organisms are susceptible to chloramphe- nicol except Pseudomanas pyoc.yaneus, proteus and Aerobacter aerogenese. It may cause serious bone marrow depression in 1:10,000 to 100,000 cases and ifused in a dose of 100 mg/kg in the newborn it causes fatal cardio-circulatorycollapse termed the "gray syndrome". Its use is indicated in typhoid fever, bacterial meningitis of unrecognized pathogen after the age of 6 months and acute epiglottitis and suspected infections with penicillin resistant staphylococci. Ampi- cillin is a safer and fairly effective alter- native for the above conditions except in the treatment of infections with penicillin resistant staphylococci.

6. Ampicillin It is a broad spectrum synthetic

penicillin. In addition to the antibacter- ial spectrum of penicillin, it is effective against gram negative bacilli especially H. influenzae. It is ineffective against penicillinase producing staphylococci, Pseudomonas pyocyaneus, the Klebsiella- aerobacter group and some strains of E. eoli.It is very safe and can be used both orally and pxrenterally but the solution

248 INDIAn JOURNAL OF PEDIATRICS VOL. 39, No. 294

for parenteral use is stable for 4 hours only. Ampicillin is indicated in patients with septicaemia and meningitis above the age of 6 months, typhoid fever, urinary tract infections and lower respiratory infections in infants.

7. Kanamycin It has a broad antibacterial spec-

trum except against Pseudoraonas pyocyaneus, pneumococcus, streptococcus and H. influenzae. There are reports to suggest that some strains of E. coli and proteus have become resistant to kanamycin. It is potentially nephro-and ore-toxic but relatively better tolerated in the newborn and infants. In combination with penicillin it is the drug of choice as initial therapy for septicaemia and/or meningitis in infants below the age of 6 months.

8. Gentamicin sulfate It provides the broadest possible

antibacterial spectrum and is effective against most gram positive and nega- tive organisms including penicillin resistant staphylococci and P~eudomonas pyocyaneus. Like kanamycin it is nephro- and oto-toxic (vestibular dysfunction) and there are no problems regarding storage and stability. It is expensive and should be reserved for life threaten- ing situations.

9. Antistaphylococcal agents The infection with penicillin resis-

tant organisms should be suspected if it is acquired in the hospital or through personnel working or visiting the hospital, in cases of pyoderma in associa- tion with septicaemia and bronchopneu- monia unresponsive to peniciUin or ampicillin and showing characteristic

radiological appearances. The effective antibiotics are listed in the order of their preference:

(a) Methicillin followed by oral cloxacillin.

(b) Bacitracin in infants below the age of 1 year.

(c) Cephalosporidine and cepha- lothin.

(d) Chloramphenicol and erythro- mycin.

(e) Oleondomyein. (f) Kanamycin.

a and b are not easily available in India.

10. Antibiotics for Pseudomonas pyocyaneus infections

Pseudomonas pyocyaneus infection should be suspected in a baby who has been nursed in the incubator and becomes sick, in hospital acquired in- fection of meningo-myelocoele and following surgical procedures. The appearance of grayish-black gangrenous lesions on the skin are characteristic of Pseudomonas pyocyaneus septicaemia. Gentamicin, carbenicillin and polymyxins in that order are the drugs of choice. While treating Pseudomonas pyocyaneus meningitis with polymyxin, the drug must be administered intratheeally since it does not cross the blood brain barrier.

Pract ica l Approach T o w a r d s Choice o f Ant ibiot ics in Var ious Clinical condi t ions

Since there are difficulties in making an aetiologieal diagnosis due to non availability of bacteriological facili- ties to most general practitioners, emphasis shall be placed on the choice of initial therapy prior to identification

SlNGH-- ANTIBIOTICS IN PEDIATRIC PRACTICE 5 4 9

of micro-organisms. In any case, in

many serious infections, therapy must be started immediately after taking cultures but without awaiting their reports.

1. Neonatal infect,ons The response of the neonate to an

infection is very different from that of an older child and common pathogens are gram negative bacilli including E. coli, proteus, klebsiella, paracolon, Streptococcus faeealis, Pseudoraonas pyocya- neus and gram positive staphylococci.

Medications should not be administered more frequently than 12 hourly during 0-14 days of age due to poor hepatic conjugation and slow renal excretion. Sulfonamides, chloramphenicol, nitro- furantolns and novobiocin should be avoided in the neonatal period.

Kanamyein 15 mg/kg/day for 10o14 days along with crystalline penicillin 50,000 units/kg./day is the drug of choice for

acute systemic infections and septicaemia in the newborn. Ampicillin may be

substituted for pen:'cillin. I f response to this combination is poor and if Pseudo- monaspyocyaneus or staphylococci are the suspected pathogens, gentamicin 5-6 rag/ kg/day or methicillin should be used. In infants beyond the neonatal period, ampicillin alone or with kanamycin is desirable to ensure effective coverage against H. influenzae. Penicillin with chloramphenicol is the second alter- native.

2. Respiratory infections In recent years it has been increa-

singly realized that most acute respira-

tory illnesses in children are due to

viruses rather than bacteria. This has necessitated a critical reassesment of the use and the limitations of antibiotics in

the treatment of these infections. The critical question, however, is how to

distinguish reliably whether one is dealing with viral or bacterial respira- tory infections ?

(a) Upper Respiratory Infections I. Acute nasopharyngitis

(common cold)

There is no role of anti- biotics here.

II . Acute tonsillo-pharyngitis

I f a child above the age of 3 years develops high fever, sore throat and

cough without coryza he should be suspected of having streptococcal pharyngitis. The presence ofpetechiae

and marked redness over the soft palate,

follicular exudates and cervical lympha"

denopathy would support the diagnosis. Although certain viruses may produce a similar clinical picture, to be on the safe side, such a patient should receive oral penicillin for a period of I0 days to safe- guard against the development of acute lheumatic fever and glomerulonephritis.

III. Acute otitis media

Penicillin alone or in combination

with sulfonamide is the drug of choice.

(b) Acute Laryngo-tracheo-bron- chitis

Acute epiglottitis as evidenced by a beefy red appearance of the epiglottis is

caused by H. influenzae and should be treated with ampicillin or chlorampheni- col. The majority of other cases of acute laryngo-tracheo-bronchitis are due to viruses and antibiotics should be with~ held for a period of 48 hours. I f the condition worsens or a bacterial

pathogen is isolated, an appropriate antibiotic should be administered.

250 INDIAN JOURNAL OF PEDIATRICS VOL. 39, No. 294

(c) Lower Respiratory Infections

I. Acute bronchiolitis. There is no evidence to suggest

that antibiotics modify the course of acute bronchiolitis.

II, Pneumonias

In infants pneumonia may be

caused by staphylococcus, H. influenzae and other gram negative organisms. The combination of ampicillin and cloxacillin or chloramplmnicol with e~ythromycin are the preferred antibio- tics in this age group. Pulmonary in- fections in older children should be managed with penicillin alone. If the patient is unresponsive to penicillin, chloramphenicol should be used and if Mycoplasma pneumoniae is suspected as the aetiologic agent, oxytetracyclin may be substituted.

3. Acute gastro-enteritis The role of antibiotics in children

with acute gastraenteritis is in dispute since no pathogens are isolated in the stools in 80-85% cases and double blind therapeutic trials have shown that placebos are as effective as antibiotics. In the management of acute diarrhoeal disorders, emphasis should be placed on prevention and correction of fluid and electrolyte disturbances, biochemical control and dietary treatment of tem- porary lactose intolerance. The non- specific harmless agents like Lomotil and Piptal are recommended. If an infective aetiology is suspected, neomycin or colistin (walamycin) is recommended.

4. Urinary tract infections (a) Acute urinary tract infection.

Sulfa triad or sulfisoxazole 120-150/ mg/kg]day in 4 divided doses for 3-6

weeks. Urine culture should be repeated after 8-12 weeks. Ampicillin and nitro- furantoins are other alernatives depending upon the sensitivity reports. In the newborn, kanamycin or ampicillin

are the drugs of choice for urinary tract infection.

(b) Recurrent urinary tract in- fections.

These patients must be investigated fully to determine any structural defect which may be perpetuating the infection and must be corrected surgically. After eradicating the organisms by using specific bactericidal agent, the urinary antiseptics like nitrofurantoin, mandela- mine, or nalidixic acid should be given for a period of a few weeks to years.

5. Pyogenic meningitis In the neonate the same schedule

as outlined for septicaemia should be followed. The common pathogens caus- ing meningitis beyond 3 months of age are pneumococci, menlngococci, and H. influen~ae. Ampicillin alone in the dose of 100 mg.ikg. I.V. stat and then 50 mg./kg. I.V. 6 houryl is the drug of choice. A combination of benzyl peni- cillin 250,000 units/kg./day and chloram- phenicol 100mg/kg]day I.V. 6 hourly is an alternative.

Prophylac t i c use o f Ant ib iot ics There is considerable evidence to

suggest that the disadvantages of prophy- lactic antibiotics far outweigh their ad- vantages except in a few well defined situations. Their hazards include mask- ing of infection without its eradication, emergence of resistant strains, alteration, of bacterial flora of the gut with superin- fection and drug toxicity.

SINGH~AN't ' IBIOTIC IN PEDIATRIC PRACTIC1g '~51

(a) Prophylactic antibiotics are not only use- less but dangerous in tke fotlowing situa- tions: Viral exanthemata, severe malnu-

trition, patients on steroids, unconscious child, indwelling catheter, prematurity and routine pre- and post-operative care.

In these situations effective epide- miologic measures for asepsis and isola- are more useful than antibiotics.

(b) Doubtful value Early rupture of the membranes

with more than 24 hours delay in the bkrth of the baby, intubation and difficult resuscitation, following exchange trans- sion and open heart surgery, before bowel surgery.

(c) D~nite value The use of long acting penicillin

(benzathin pencillin 12,00,000 units after every 3-4 weeks uptil the age of 20 years) is established in the prophylaxis of rheumatic fever. Penicillin is also indi- cated for prevention of endocarditis in susceptible patients and immediately before or after exposure to gonorrhoea. Sulfonamides are also recommended for close contacts of patients with meningo- coccal septicaemia.

Conclusions

It nceds to be emphasized that no antibiotic is entirely safe. They should

be used only when indicated because un. necessary exposure to the antibiotic results in the evolution of resistant bacte- ria with cross infection in susceptible in- dividuals and loss of utility of the parti-

cular antibiotic. Lastly, if a patient on antibiotics fails to respond or his clinical condition worsens, the tollowing possibi. lities should be seriously considered:

I. Wrong diagnosis or wrong sus- picion of the offending patho- gen. The possibility of tuber- culosis and noninfective illnes- sess like allergic, collagen and malignant disorders should be considered.

2: Wrong antibiotic.

3. Suboptimal dose of appropriate antibiotic.

4. Complications of original disease eg. embolization in bacterial endocarditis rupture of pneumatocoele in staphylo- coccal pneumonia.

5. Complications of the antibiotic especially in the newborn.

6. Presence of an underlying an- atomical defect i.e. obstructive uropathy, pneumonitis in atelactatic lung.

7. Collection of pus--unless it is drained, no amount of antibio- tics are likely to dry it.