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1. SINUSITIS, BRONCHITIS, AND PNEUMONIA
SINUSITIS
Infection of the paranasal sinuses is a troublesome, often recurrent
condition estimated to occur in at least 25% of adults.3 Although these
patients rarely require hospitalization, we estimate, using estimates from
Great Britain, that more than 1,000,000 work days are lost in the United
States each year because of sinusitis.4 Often associated with chronic
bronchitis, some believe that sinusitis is a reservoir of organisms responsi-
ble for acute bronchial infections.
The diagnosis of acute sinusitis is usually based on clinical findings,
although radiologic studies may provide additional information. Gram
stain and cultures of nasal secretions are unreliable because they are often
contaminated by organisms resident in the nasopharynx. Thus, the antibi-
otic treatment of acute sinusitis is empirical, based on knowledge of the
likely pathogens and ability of the drug to concentrate in sinus mucosa and
secretions.
Streptococcus pneumoniae and Hemophilus influenzae have long been
implicated in acute and chronic sinusitis. In recent years, however, several
studies have demonstrated that in some instances anaerobic organisms also
play an important etiologic role.5'6 Frederick and Braude reported that 52%
of patients had anaerobic organisms in chronically infected sinus secre-
tions. These anaerobes-peptostreptococci, fusobacteria, Bacteroides, and
Veillonella-were commonly found mixed with the aerobic organism.
Fungi and viruses occasionally infect the sinuses. Mycoplasma sp. and
Chlamydia sp. may contribute to sinus infection, although their role is less
well defined. In addition to microorganisms, allergy, such congenital
abnormalities as a deviated nasal septum, or both are considered important
contributing factors. The newer analogues, doxycycline and minocycline,
have the advantage of higher activity against both aerobic organisms.2'7
They are more completely absorbed from the gastrointestinal tract and
achieve antibacterial levels in infected sinus muscosa and secretions, pre-
sumably because their high lipid solubility eases transport into and across
cell membranes.8'9 This property is important, because for an antibiotic to
be effective in sinusitis, concentration in the mucous membrane itself as
well as in secretions is important. Doxycycline is our antibiotic of choice
for sinusitis. Although minocycline has also proved effective, because
vestibular dysfunction is frequent we do not use it in outpatients.10
A favorable feature of doxycycline, as opposed to tetracycline hydro-
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157

2. 158 G. A.
PANKEY~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
chloride and the other analogues, is that it does not accumulate in the
presence of renal impairment. Thus, neither renal function studies nor
dosage adjustments before instituting therapy are necessary, as they are
with the other tetracyclines. However, dosage changes are necessary in
patients receiving such antiepileptic drugs as carbamazepine, diphenylhy-
dantoin, and phenobarbital. The metabolism of doxycycline by the liver is
enhanced by these agents and larger dosages are needed to maintain
effective blood and tissue levels.1"
Because its serum half-life is 18 to 22 hours, doxycycline can be taken
only once a day after the initial loading dose of 100 mg. twice the first
day. Depending on the patient's weight, we generally follow this with 100
mg., once or twice daily, for 14 days. This is longer than my previous
recommendation'2 but necessary to eradicate the more difficult anaerobic
bacteria.
We usually instruct patients to take doxycycline with meals, because this
reduces the chance of nausea and does not significantly impair the drug's
absorption. However, divalent cations such as the ferrous ion do impair
absorption, and two to three hours should separate the administration of all
tetracyclines and ferrous sulfate.
Most patients with acute sinusitis do very well on a combination of
doxycycline and local systemic decongestant therapy. However, surgical
drainage may occasionally also be necessary, particularly when symptoms
are severe and there is radiologic evidence of sinus clouding.
In patients with chronic sinusitis, surgical intervention is often required
for polyps, cysts, or other pathological changes that impair sinus drainage.
Following these procedures, treatment with doxycycline (100 mg./day)
may be initiated for four to six weeks. On the whole, results of antibiotic
therapy in chronic sinusitis are not as dramatic as in acute disease except
during periods of acute exacerbation.
BRONCHITIS
As with sinusitis, acute bronchial infection is common in the adult
population. Many elderly patients also suffer from chronic bronchitis,
emphysema, or both, and have acute exacerbations of bronchitis.
Because sputum cultures are frequently unreliable in defining etiologic
organisms, the initial diagnosis of acute bronchitis is usually clinical.
Sputum Gram stain and culture are of greater importance for the occasional
patient who does not rapidly respond to initial antibiotic therapy.
Bull. N.Y. Acad. Med.
158 G. A.PANKEY

3. SINUSITIS, BRONCHITIS, AND PNEUMONIA
Common pathogens associated with acute bronchitis in patients with
underlying chronic bronchitis or chronic obstructive pulmonary disease are
S. pneumoniae and H. influenzae. M. pneumoniae and various viruses also
play a role in some patients. All of these organisms may occur alone or in
combination.13 Anaerobic bacteria do not appear to be associated with
acute exacerbations of chronic bronchitis. 14
While ampicillin is widely used, unlike doxycycline, it is ineffective
against M. pneumoniae, penetrates purulent sputum poorly, must be taken
frequently, may sensitize the patient to penicillin, and causes an idiosyn-
cratic rash in some hyperuricemic patients receiving allopurinol. Amoxicil-
lin penetrates purulent sputum and apparently does not have the idiosyncra-
tic rash problem, but adults usually must take 500 mg. every eight hours,
and we prefer to reserve it for the rare patient who fails to respond to
doxycycline. Chodosh has demonstrated that doxycycline and amoxicillin
appear to be equivalent in efficacy.15 Perhaps this is related to the bron-
chial mucosal concentration as well as to purulent and mucoid secretion
concentration of these drugs. 16,17
The safety of doxycycline in patients with renal impairment is signifi-
cant in patients with chronic bronchitis, many of whom have some degree
of renal dysfunction.18 The progressive decrease in renal function with
aging (already 30% at age 65)19 also must be considered when selecting an
antibiotic for these outpatients. Thus, in my view, tetracyclines other than
doxycycline should be avoided in such cases.
Like most physicians treating chronic bronchitis, it is our practice to
write a prescription for patients to use with acute exacerbations, instructing
them to start antibiotic therapy as soon as signs of infection develop, such
as increased cough and purulent sputum production. Rather than ampicil-
lin, doxycycline is used to treat these acute exacerbations. We use 100 mg.
every 12 hours for two doses, followed by 100 mg./day for at least 10 days
or for several days after the sputum has become nonpurulent. Patient
compliance is usually satisfactory with this once-daily dosage schedule. If
symptoms do not improve within 48 hours, patients are instructed to report
for examination and sputum evaluation. In such cases there is the chance
that a virus or tetracycline-resistant Gram-negative bacilli such as
Pseudomonas aeruginosa, Klebsiella, and Proteus are the pathogens. Al-
though bronchial infections due to the latter organisms are infrequent, the
physician should always be alert to the possibility. In our experience, they
are most likely in adult cystic fibrosis patients, patients with bronchiectasis
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4. 160
G. A. PANKEY
associated with chronic bronchitis, and patients with chronic obstructive
pulmonary disease who develop acute bronchitis while in the hospital.
The role of intermittent or continuous antibiotic therapy in suppressing
acute exacerbations of chronic bronchitis is still not established. There is
some evidence that this therapy reduces morbidity, but insufficient data are
available to answer whether it helps retard destruction of lung tissue. A
major concern is that continuous antibiotic therapy may result in bacterial
strains resistant to antibiotics.
ADJUVANT THERAPY
Obviously, the importance of preventing or lessening bronchial irritation
must be emphasized. Especially important is the avoidance of air pollu-
tants (including cigarette, cigar, and pipe smoke), humidification of in-
haled air, and postural drainage. Bronchodilators are useful in some pa-
tients, but the role of expectorants is less well established.
MYCOPLASMAL PNEUMONIA
The organism M. pneumoniae is estimated to cause more than one third
of all pneumonias among civilian populations. It is also an etiologic agent
in pharyngitis and bronchitis. Mycoplasmal pneumonia can occur at any
age, but it is more common among adolescents and young adults and is
unusual after the age of 50. The clinical course is usually self-limiting, but
it can result in prolonged disability and, occasionally, serious complica-
tions such as meningitis and hemolytic anemia.21
Like sinusitis and bronchitis, the initial diagnosis of mycoplasmal
pneumonia is clinical, and its antibiotic treatment is empirical because
culture techniques may not be available and serologic tests require both
acute and convalescent sera to confirm the diagnosis.
It is characteristic of mycoplasmal pneumonia that symptoms such as
fever, cough, malaise, and headache develop slowly over a period of days.
Sputum Gram stains reveal insignificant numbers of bacteria, although the
sputum may be purulent. Certainly, any adolescent or young adult who
presents with such symptoms and signs should have a chest roentgeno-
gram. If a diagnosis of a "walking" pneumonia is made, M. pneumoniae
is the most likely agent, although other organisms, such as Mycobacteri-
um tuberculosis, must be considered in the differential diagnosis.
The tetracyclines and erythromycin are the most appropriate antibiotics
to treat mycoplasmal pneumonia. Both have in vitro activity against M.
Bull. N.Y. Acad. Med.
160 G. A.PANKEY

5. SINUSITIS, BRONCHITIS, AND PNEUMONIA
pneumoniae and are equally effective clinically. Clindamycin has been
shown to be ineffective,22 but the in vitro development of resistance
against erythromycin has not been a problem clinically.23
Unlike many bacterial infections, antibiotic therapy of M. pneumoniae
appears to have no effect on eradication of the organism, but it does
shorten the duration of symptoms and signs, which results in decreased
morbidity. Whether tetracycline or erythromycin prevents complications of
mycoplasmal pneumonia has not been determined.
We regard one of the tetracyclines as the antibiotic of choice because
these drugs are effective against such rickettsial and chlamydial disease as
Q fever and psittacosis, which can mimic mycoplasmal pneumonia. Our
pneumococcal isolates have remained susceptible in vitro to tetracycline.
In addition to the safety factors, doxycycline concentrates well in the
lung and is our tetracycline of choice for mycoplasma pneumonia. The
dosage in ambulatory patients is 100 mg. every 12 hours for one week.
Symptomatic improvement usually occurs within 48 to 72 hours, although
clearing of chest roentgenograms is frequently slower. Although equally
effective, erythromycin tends to cause more gastrointestinal side effects
and requires a dosage schedule of four times a day.
In the patient who requires hospitalization, intravenous doxycycline (200
mg./day administered in a 400 cc. infusion) may be used if there are
symptoms of nausea and vomiting. However, because oral administration
of this drug provides equivalent serum and tissue levels, the usual oral
dosage is resumed once gastrointestinal symptoms have abated.
DISCUSSION
DR. L. D. SABATH. You commented that it was worthless to examine
the purulent postnasal drip for selecting therapy, and then later you men-
tioned that patients who failed to respond to therapy prescribed over the
phone for bronchitis should come into the office to have the sputum
examined. Just how helpful is it to culture purulent secretions in selecting
therapy?
DR. PANKEY. If patients with sinusitis do not respond, we ask them to
come back in 48 hours for roentgenograms of the sinuses. Frequently,
surgical drainage is required. In chronic bronchitis, where the acute
exacerbation does not respond, we frequently find that we are dealing with
other Gram-negative rods, as in the cystic fibrosis patient. Perhaps we are
dealing with an area of bronchiectasis associated with chronic bronchitis,
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6. 162
G. A. PANKEY
and the patient, in fact, now has Pseudomonas aeruginosa or resistant
Klebsiella sp. or Proteus sp. Obviously, the immunosuppressed patient is
entirely different, as is the patient who has been in the hospital. Most of
the time the cultures done in 48 hours for the patient who does not respond
initially are not helpful, as you have suggested.
DR. HAROLD C. NEU. You did not mention how long you treat these
various entities: the sinusitis, the mycoplasmal pneumonia, and the bron-
chitis.
DR. PANKEY. With the recognition of the role of the anaerobes in
sinusitis, we prolong our treatment to two weeks because anaerobic infec-
tions, by nature, require long therapy. Obviously, some patients are going
to have surgery, which is the prime therapy with very few exceptions for
any anaerobic infection. With bronchitis we treat 10 days, or at least two
or three days beyond the disappearance of the purulent sputum. We treat
mycoplasmal pneumonia for one week. Of course, the length of therapy is
arbitrary for all of these infections.
DR. NEU. If the patient's sputum becomes purulent during a time of
year when this is common, would you arbitrarily tell them to resume
therapy?
DR. PANKEY. Yes. The hospital or office visit for culture and sensitivity
testing for one organism may cost the patient $20 to $30. If patients do not
have a prescription to fill in order to start therapy, they will not come into
the office until they get seriously ill. Many of our patients travel a lot; they
may be in another city when the acute exacerbation occurs and not know
where to go for treatment. From a practical standpoint, giving them a
prescription has worked very nicely. One has to be careful about what
antibiotics one prescribes in a refillable prescription. We do not like to
prescribe ampicillin or any of the penicillins in refillable prescriptions
except for people who receive prophylaxis for rheumatic fever.
DR. FRANK M. CALIA. It may be that I see a different patient population
at a Veterans Administration hospital, but when our patients fail to re-
spond to tetracycline, very often it is not entirely due to the infection. We
get all kinds of aerobic Gram-negative rods and occasionally Staphylococ-
cus aureus from sputum cultures, which are the result of colonization, but
our patients do not respond, because they continue to smoke or have a very
poor pulmonary toilet. If we manipulate those situations rather than the
chemotherapy, they do respond.
DR. PANKEY. I think that is critical. The other therapy is just as
Bull. N.Y. Acad. Med.
162 G. A.PANKEY

7. SINUSITIS, BRONCHITIS, AND PNEUMONIA 163
important as the antibiotic therapy. We have great difficulty with smoke
and other air pollutants. We use bronchodilators if patients are wheezing,
and we try to have air humidified.
DR. NEU. It seems to me that one of our failures in administering these
drugs in bronchitis is not giving a large enough dose to decrease the
inflammatory response significantly. For instance, some of the Hemophilus
MIC values are up around 1 to 1.5 ,ug./ml. With some people, if one is
using a drug like doxycycline, perhaps the dosage should be 200 mg./day
for the first two or three days. As for tetracycline hydrochloride, according
to my review of the literature, if 2 gm. are not given for the first several
days, it is no wonder that the regimen is not effective. Bronchial drainage,
smoking cessation, bronchodilators, and air humidification are also very
important, of course. But effective antibiotic therapy at the beginning of an
illness decreases the number of bacteria and thus allows the secretions to
become more viscid.
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