Adherence to Physicians' Instructions as a Factor in Managing Streptococcal Pharyngitis

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Adherence

to Physicians’

Instructions

as a Factor

in Managing

Streptococcal

Pharyngitis

Adnan S. Dajani, MD

ABSTRACT. Adherence to physicians’ instructions,

in-cluding taking medications as prescribed, is essential for

the proper treatment of streptococcal pharyngitis and the

prevention of rheumatic fever. Nonadherence can be in

many forms, including failure to have prescriptions

filled, omission of doses, errors in dosing or

administra-tion time, and premature discontinuation of medication.

Adherence is dependent on the physician, the patient,

the illness, and the medication. Proper communication by the physician and prescribing inexpensive medica-tions that can be taken once or twice daily are simple, yet important actions that improve adherence. Pediatrics

199697:976-980.

ABBREVIATION: GAS, Group A streptococci.

Op timal management of any infectious disease is

dependent on the physician arriving at a proper

diagnosis, including establishing an etiologic agent,

prescribing effective therapy, and on the patient

ad-hering to the physician’s instructions. The extent to

which a patient’s actions coincide with the medical

advice has been termed compliance. Because compli-ance implies a tendency to yield to others, especially

in a weak and subservient way, the term adherence

(fidelity, assent, concurrence) is preferred and will be

used in this article.

Frequency and Types of Nonadherence

Nonadherence to medical advice is as old as

re-corded history. Hippocrates stated “Keep watch also

on the fault of patients which often makes them lie

about the taking of things prescribed.” Many reports

suggest that more than 50% of patients are

nonad-herent to taking medications as prescribed.4

Non-adherence can be in many forms: not filling prescrip-tions at all; omission of doses; errors in dosage,

timing, or sequence; taking the wrong medication;

and premature discontinuation of the medication.

Measurement of Nonadherence

Assessment of patient adherence can be made in

different ways.

1. Interview of the patient or parent is commonly

used, but is very subjective. Furthermore, patients

responses may not reflect actual practices.

From the Division of Infectious Diseases, Children’s Hospital of Michigan and the Department of Pediatrics, Wayne State University School of Med-icine, Detroit.

2. Counting (or measuring) unused pills (or liquid

formulation) at certain times during the course of

treatment. Whereas this method is somewhat

more objective, it is also not a true representation

of adherence. Used up pifis or liquid may have

been diverted other than to the patient’s

gastroin-testinal tract.

3. Spot-testing of serum or urine for medication,

preferably without prior knowledge of the patient

that a sample wifi be obtained. Such testing

as-sures that medication had been taken, but will not

determine if the quantity was appropriate.

4. Medication-monitoring devices have been

devel-oped to measure patient adherence. The medica-tion monitor is a specially designed dispenser containing a minute amount of radioactive mate-rial and photographic film to record the regularity

with which medication is removed.5 The

Medica-tion Event Monitor Systems are standard pill

bot-ties with microprocessors in the cap to record

every bottle opening as presumptive dose.6 Both devices are very effective and objective methods for assessing adherence; unfortunately, they are expensive and not readily available.

TREATMENT OF STREPTOCOCCAL PHARYNGITIS

AND PREVENTION OF RHEUMATIC FEVER

Adherence to Oral Antimicrobial Treatment of Acute

Infections

Since the demonstration that penicillin treatment

prevents acute rheumatic fever,7’ several studies re-ported on patients’ (or parents’) adherence to treat-ment of streptococcal infections with oral penicillin preparations. A study in 1955 by Mohler et a!9

inves-tigated adherence in 245 children and adults with

Group A streptococci (GAS), pharyngitis, or otitis media who were being treated with 250 mg tablets of penicillin G three times daily for 7 days. Interview of patients and parents at the conclusion of treatment

showed that 84 (34.3%) failed to take the full 7-day

course. Of the nonadherent patients, 56% took

med-ications for less than 5 days. Adherence in children

was better than in adults (67.7% vs 50%). As the

study progressed, additional education and

instruc-tion of patients and parents was introduced, but this did not result in a significant improvement of

adher-ence. The most common reason for nonadherence (in

37% of instances) was the impression by the patient

or parent that they felt well and did not need the

medication any longer. Other reasons for

nonadher-ence included carelessness (27%), insufficient money

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(17%), refusal to swallow tablets (11%), and misun-derstanding of the instructions (8%).

In a subsequent, often cited study, Bergman and Werner,’#{176}studied adherence to penicillin given three

times daily for 10 days by mouth (liquid formulation

of penicillin V in children under 6 years of age and penicillin G tablets for children over 6 years) to treat

presumed GAS infections. Medications were

dis-pensed free of charge. Home visits were made on

days 3 or 4, 6 or 7, and 9 or 10 at which time parents

were interviewed, pills (or liquid) counted (mea-sured), and urine was obtained to assay for the pres-ence of penicillin. Interviews with families indicated

that the overwhelming majority knew the proper

directions for giving the medications (95%), knew that the medication was penicillin (90%), claimed all

the doses were given (83%), and had adequate

knowledge of the diagnosis (80%). Only 22%

indi-cated that they had difficulty in giving the

medica-tions. However, results of pill counting (or liquid

measurement) and urine testing were at sharp vari-ance with the results of the interviews. Even as early

as 3 or 4 days after starting therapy, >50% of patients

were nonadherent, and nonadherence increased with

time. There was a good correlation between pill

count and urine testing. A striking relation between

age and adherence was noted: the median age for

adherent patients was 5 years, for nonadherent pa-tients, it was 2 years.

Table I summarizes data from five studies

be-tween 1963 and 1969 that addressed adherence to 10

days of oral penicillin for GAS infections.104

To-wards the end of therapy (day 9), adherence varied from 8% to 89%. In the two studies where sequential

observations were made, adherence declined with

time. In at least one study,14 there was a correlation of

therapeutic failure with failure to take medications.

In a subsequent study by Colcher and Bass,’5 ad-herence to three penicillin regimens was compared. The results are summarized in Table 2. The normally

informed group were instructed to give the

medica-tion three times daily for 10 days. The optimally informed group received more detailed counseling outlining the necessity that penicillin be given for 10 days to best effect a cure and prevent relapses, and were also handed written instructions. Bacteriologic

eradications were comparable for the three regimens.

However, relapses were significantly more in the

normally informed group compared with the group

receiving injectable penicillin (P .029) or the group

who was optimally informed (P = .004). The

nor-mally informed group also had the lowest adherence

rates; when compared with the optimally informed

group, the differences in adherence rates (58% and

80%) were statistically significant (P = .001).

In a recent report by Raz et a!,16 penicillin V given

as I .0-g twice daily was compared with the same

medication given as 0.5-g four times daily in the

treatment of streptococcal pharyngitis in 104 patients

older than 12 years of age. Both regimens were given

for 10 days. Adherence to prescribed medication was

90% in the group that received penicillin twice daily,

but only 58% in the group that received the

medica-tion four times daily. Resolution of symptoms at the

end of treatment was significantly better with the

twice daily regimen than with the four times daily

regimen (92% vs 77%, respectively). Similarly, erad-ication of GAS from the pharynx was significantly higher in the group that received penicillin twice

daily than in the group that received the medication

four times daily (90% vs 73%, respectively).

An additional study assessed adherence to

eryth-romycin administration to treat acute GAS

pharyn-gitis and the effect of adherence on eradication of the

organism from the pharynx.’7 Patients were

pre-scribed erythromycin estolate suspension at 20 mgI

kglday to be given twice daily for 10 days. In 75

patients who received 90% of the medication, GAS

were eradicated in 89%. The eradication rate was

reduced to 76% if about 75% of the mediation was

consumed, and to 60% if only about 50% of the

medication was consumed. This study confirms the

earlier observation by Green et aP4 that there is a

correlation of improved therapeutic efficacy with

better adherence to medication consumption. Adherence to Penicillin Prophylaxis in Patients With Rheumatic Fever

Individuals who have had a previous attack of

rheumatic fever are at very high risk of subsequent attacks if they develop GAS tonsillopharyngitis.

Therefore, secondary prevention of GAS infections is

particularly important in these patients. Injectable

benzathine penicillin G is the preferred regimen to

use,’8 but oral penicillin prophylaxis is acceptable

and widely used. Adherence to oral penicillin

pro-phylaxis wifi be reviewed.

Gordis et al’9 studied adherence in 136 children

TABLE 1. Adherence to 10 Days of Oral Penicillin for GAS

Reference Number Method Adherence (%) on Days

3 6 9

Bergman and Werner1#{176}

Leistyna and Macauly

59

162

Pill count and urine testing

Pill count and urine testing

44 46 29 31 18 8 89

Charney et al’2 Rosenstein et al*13 Green et alt14

459 331 198 Urine testing Urine testing Urine testing 81 56 88 68 Abbreviation: GAS, Group A streptococci.

* No correlation of therapeutic failure with failure to take medication.

FCorrelation of therapeutic failure with failure to take medication.

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TABLE 2. Comparison of Three Penicillin Regimens

Regimen Bacteriologic Relapsest Adherences

Failures*

Procaine and benzathine penicillin 1.2 3/100 11/100 87%

million U, IM, single dose

Penicillin V, 250 mg three times daily I /100 24/100 58%

for 10 days. Normally informed

Penicillin V. 250 mg three times daily 2/100 8/100 80%

for 10 days. Optimally informed Abbreviation: IM, intramuscular.

* Positive cultures at 9 days.

tPositive cultures at 3 and/or 6 weeks.

:1:Antibiotic present in urine at 9 days. (Data adapted from Colcher and Bass’5).

and adolescents regularly attending a rheumatic

fe-ver clinic. Patients had been placed on a regimen of

125 mg oral penicillin G daily. Random urine testing

for penicillin was performed weekly by school

nurses over a 5-month period, and also at scheduled

clinic visits. An individual was considered adherent

if 75% of urine samples had detectable penicillin,

intermediately adherent if 26% to 74% of urine

sam-pies contained penicillin, and nonadherent if 25%

of urine samples were positive. Only 32% of the

patients were adherent; 32% were intermediately

ad-herent, and 36% were nonadherent. No significant

change in individual adherence was noted over the 5-month period. There was an excellent correlation between school and clinic screening suggesting that

clinic testing is an adequate venue for assessing

ad-herence. An association was found between unkept

clinic appointments and nonadherence.

A subsequent study by the same group#{176}

at-tempted to identify demographic and medical

fac-tors that influence adherence to oral penicillin

pro-phylaxis. Among demographic factors, gender, age,

and family size had significant effects on adherence.

Males were more adherent than females (41 % versus

29%). Adherence decreased with increasing age:

cM!-dren 9 years old or younger were 46% adherent,

those 10 to 12 years old were 36% adherent, and

children 13 years or older were 31% adherent. Ad-herence was best in children from smaller families:

adherence was 42% in families with one to three

children, 33% in families with four to five children,

and only 28% in families with six or more children. There were no significant effects noted for annual

family income, educational and occupational levels,

family structure (single versus two parents), or the

presence of family problems.

Among medical factors, previous hospitalization

for the acute attack and the presence of rheumatic heart disease were significantly associated with ad-herence. A previously hospitalized patient was less

apt to be nonadherent (32%) than a nonhospitalized

patient (58%). Patients without rheumatic heart

dis-ease were 42% nonadherent, whereas patients with

heart disease were only 16% nonadherent. Patients

with rheumatic heart disease who had restricted

ac-tivity were never nonadherent. No significant effects were noted for duration of hospitalization, duration

since last attack, or maternal knowledge about

rheu-matic fever or penicillin.

DISCUSSION Factors Assodated With Nonadherence

Adherence by a patient to advice by a physician

depends on several interdependent variables: the

physician, the patient, the illness, and the medication

(Figure). These and other factors have been

dis-cussed in detail previously;’6 discussion here will be

limited to aspects relevant to streptococcal infections

and their complications.

The Physician. Physicians’ competence and

corn-munication skills are important factors in reflecting patients’ adherence. Marked variation exists among

physicians in their comprehensive knowledge of

streptococcal infections and their complications.2’

Recognition of symptoms and signs, knowledge of

streptococcal epidemiology, the appropriate

diagno-sis of streptococcal pharyngitis, knowledge of

poten-tial poststreptococcal complications, selection of ap-propriate antimicrobial agents, and the appreciation for the need (or lack of) for repeat throat cultures are essential components of a physicians’s competence.

Adequate explanation of the above components to

the patient or parent is likely to improve adherence.

The Patient. Errors and nonadherence occur more often at extremes of life. Children have to depend on others to administer medications; the elderly may

have lapses of memory or suffer self-neglect.

Women, particularly under the age of 30 years, seem

Figure. Interdependent variables that influence adherence.

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TABLE 3. Potential Outcomes of Nonadherence

Increase in treatment failures. Increase in relapses and recurrences. Increase in complications.

Increase in return visits to physicians. Increase in number of prescriptions. Increase in hospitalizations.

Increase in morbidity and mortality. Increase in health care costs. Increase in antimicrobial resistance.

to be less adherent than men.3 Education, economic,

and ethnic factors may also play a role in adherence.

In general, the less educated and the less

economi-cally privileged the individual, the lower the

adher-ence. Knowledge of the disease process and previous experience with a similar illness improve adherence. Rapidity of clinical improvement of chronic

condi-tions (gratification) may improve adherence,

whereas chronicity and severity of the illness

(de-spair) may hinder adherence. Greater attention to

educating the patient or parent regarding the illness

and the benefits of medications may contribute to

better adherence.

The illness. Because symptoms of streptococcal

pharyngitis are usually self-limited, many patients

discontinue medications a few days after starting

treatment but before completion of the

recom-mended 10-day period for oral penicillin or

erythro-mycin. The marked reduction in the incidence of

acute rheumatic fever and poststreptococcal

glomer-ulonephritis in the United States has resulted in a

more relaxed attitude about streptococcal infections,

both by patients and physicians.

Patients who had a previous attack of rheumatic

fever require prolonged, perhaps lifelong,

prophy-laxis. Patients with chronic illnesses are prone to

lapses in adherence, especially if the treatment is

prophylactic rather than therapeutic. The

observa-tions of Gordis et a!2#{176}are of special interest because

they pointed out two important medical factors that

contributed significantly to improved adherence to

rheumatic fever prophylaxis. The presence of

rheu-matic heart disease, particularly if associated with

restricted activity, resulted in excellent adherence to

prophylaxis. Previous hospitalization for the acute

attack also improved adherence. These observations

suggest that the severity of the ifiness improves

pa-tient adherence.

The Medication. A number of factors related to the medication itself are important determinants of

ad-herence. The mode of administration (oral versus

parentera!) is important. A single injection of

benza-thine penicillin is therapeutic for streptococcal

phar-yngitis and obviates concerns about adherence for

that specific infection. Unfortunately, because this

injection can be painful, adherence to subsequent use

of this regimen may be suboptimal. Palatability of oral medications is critical, particularly in children. Tablets and capsules are usually more palatable than

liquids or suspensions but not practical for younger

children. The smell, taste, and consistency of the

liquid formulation are all important variables that

influence adherence.

The frequency of daily administration of a

medi-cation has been shown to contribute substantially to

poor adherence. Two studies indicated that once

daily administration of medications resulted in

ad-herence in about 90% of patients, whereas four times

daily administration resulted in adherence in only

30% to 40% of patients. Administration two to three

times daily resulted in intermediate adherence rates,

with twice daily administration being superior to

three times daily administration.2’6 The report by Raz

et al’6 suggests that for the treatment of acute

strep-tococcal pharyngitis in adult patients, penicillin V

given twice daily was significantly superior to

peni-cillin V given four times daily in eradication of the

organism from the pharynx and in resolving

symp-toms. For children attending school, and for parents

who work during the day, any medication given

more than twice daily will probably not be taken as

often as desired.

The rate of nonadherence becomes greater when

the treatment period is prolonged. For oral penicillin

and erythromycin, 10 days of treatment for GAS

pharyngitis are necessary.’8 Because most patients

feel better within a few days of starting treatment,

there is a tendency by patients and parents not to

complete a full course. The larger the number of

medications a patient takes, the higher the risk of

nonadherence. If a patient is to receive several

med-ications, it is imperative to explain the importance of

each and the reason for its use. The development of

adverse or unpleasant side effects is a deterrent to

adherence. Although some of these adverse effects

may not be medically serious (such as loose stools,

rashes, and abdominal discomfort), patients often

become nonadherent as a result of a perceived

prob-lem. Finally, the cost of a medication is a major factor

in adherence; expensive medications are less apt to

be purchased and less likely to be taken for the total

duration.

Consequences of Nonadherence

Nonadherence to physicians’ instructions,

indud-ing the inappropriate consumption of medications,

has a potential to cause a number of problems that

affect the patient and society. Some of these potential problems are listed in Table 3. Several of these areas

have been discussed in previous publications”’4 and

wifi not be discussed further here.

ACKNOWLEDGMENTS

Dr Floyd W. Denny kindly reviewed the manuscript and

Deborah F. Riley provided excellent secretarial assistance.

REFERENCES

1. Hussar DA. importance of patients compliance in effective antimicro-bial therapy. Pediatr Infect Dis J.19876:971-975

2. Ayd FJ. Once-a-day neuroleptic and tricyclic antidepressant therapy. mt

Drug Ther Newslett. 1972;7:33-40

3. Blackwell B. Patient compliance. N Engl IMed. 1973289:249-232 4. Stewart RB, Cluff LE. A review of medication errors and compliance in

ambulant patients. Clin Pharm Ther. 1972;13:463-468

5. Moulding T, Onstad D, Sbarbaro JA. Supervision of outpatient drug therapy with the medication monitor. Ann mt Med. 1970;73:559-564 6. Cramer JA, Mattson RH, Prevey ML, Scheyer RD. Ouellete VL. How

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often is medication taken as prescribed? A novel assessment technique. JAMA. 1989261:3273-3277

7. Denny FW, Wannamaker LW, Brink WR, Rammelkamp CH, Custer EA. Prevention of rheumatic fever. Treatment of the preceding streptococci infection. JAMA. 1950;143:151-153

8. Wannamaker LW, Rammelkamp CH, Denny FW, et al. Prophylaxis of

acute rheumatic fever by treatment of the preceding streptococcal

in-fection with various amounts of depot penicillin. Am IMed. 1951;10:

673-695

9. Molder DN, Wallin DG, Dreyfus EG. Studies in the home treatment of

streptococcal disease. I. Failure ofpatients to take penicillin by mouth as prescribed. N Engi JMed. 1955;252:1116-1118

10. Bergman AB, Werner RJ. Failure of children to receive penicillin by mouth. N Engl IMed. 1963268:1334-1338

11. Leistyna JA, Macauly JC. Therapy of streptococcal infections. Am IDis Child. 1966;111:22-26

12. Charney E, Bynum R, Eldredge D, et a!. How well do patients take oral penicillin: a collaborative study. Pediatrics. 1%7;40:188-195

13. Rosenstein BJ, Markowitz M, Goldstein E, et al. Factors involved in treatment failures following oral penicillin therapy of streptococcal pharyngitis. IPediatr. 1968;73:513-520

14. Green JL, Ray SP, Charney E. Recurrence rate of streptococcal pharyn-gitis related to oral penicillin. IPediatr. 1%9;75:292-294

15. Coicher IS, Bass JW. Penicillin treatment of streptococcal pharyngitis. A comparison of schedules and role of specific counseling. JAMA. 1972;

222:657-659

16. Raz R, Elchanan G, Colodner, et al. Penicillin V twice daily vs. four times daily in the treatment of streptococcal pharyngitis. Infect Dis Clin Pract. 1995;4:50-54

17. Derrick CW, Dillin HC. Erythromydn therapy for streptococcal

phar-yngitis. Am IDis Child. 1976;130:175-178

18. Dajani AS, Bisno AL, Chung KJ, et al. Special report Prevention of

rheumatic fever. A statement for health professionals by the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young. Circulation. 1988;78:1082-1086

19. Gordis L, MarkOWitZ M, Ulienfeld AM. Studies in the epidemiology and preventabifity of rheumatic fever. IV. A quantitative determination of compliance in children on oral penicillin prophylaxis. Pediatrics. 1969;43:173-182

20. Gordis L, Markowitz M, Lilienfeld AM. Why patients don’t follow

medical advice: a study of children on long-term antistreptococcal prophylaxis. IPediatr. 1969;75:957-968

21. Gordis L, Desi L, Schmerler HR. Treatment of acute sore throats: a comparison of pediatricians and general physicians. Pediatrics. 197657:

422-424

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1996;97;976

Pediatrics

Adnan S. Dajani

Pharyngitis