PNEUMOCYSTIS PROPHYLAXIS OVERVIEW
IntroductionIn spite of recent improvements in treatment, pneumocystis
pneumonia remains the most frequent cause of death in people with
HIV infection. In addition, all currently available treatments
have potentially serious toxicities associated with them.
Therefore, the best approach to dealing with pneumocystis is to
avoid getting it by properly using an effective prophylaxis
(preventive treatment) in all persons at risk of developing the
infection.
This article provides an overview of current information and
controversies about approved and experimental prophylaxis for
pneumocystis. Because no currently available option is ideal, we
discuss the potential advantages and disadvantages of each
approach.
When to Use Pneumocystis Prophylaxis
The official recommendation of the U. S. Public Health
Service is that adults should use a prophylaxis against
pneumocystis if they have: (1) a T-helper count of 200 or less,
or (2) a T-helper cell percent of less than 20, or (3) a previous
episode of pneumocystis.1 (The T-helper cell percent is a
laboratory marker of disease severity that doctors often take
into account when recommending various treatments or prophylaxis.
It measures the percent of all the white blood cells known as
lymphocytes that are T-helper cells.)
There are additional situations in which prophylaxis may be
helpful, although there is no consensus among physicians in this
area. A recent survey of over 80 physicians and other health-
care providers practicing in the San Francisco Bay Area
demonstrated the following trends in pneumocystis prophylaxis:2
* Seventy-seven percent of the responding health-care
providers would offer prophylaxis to patients with any AIDS-
defining opportunistic infection, even if they did not meet the
criteria outlined in the official recommendations described
above.
* Fifty-eight percent would offer prophylaxis to patients
with any AIDS-related malignancy irrespective of whether or not
they met the official criteria.
* While approximately 80-90 percent would offer prophylaxis
to patients with under 200 T-helper cells, whether symptomatic or
not, less than half of those responding would do so for patients
with less than 20 percent T-helper cells and no other reason for
prophylaxis.
* Approximately half would offer prophylaxis to symptomatic
patients with more than 200 but less than 300 T-helper cells;
only about 30 percent would offer prophylaxis to asymptomatic
patients in that range. Few would recommend prophylaxis for
patients with more than 300 T-helper cells.
A Note About Infants
Current recommendations suggest that all infants and
children should receive pneumocystis prophylaxis when their T-
helper cell count falls below 500. However, an important study
presented at the Sixth International Conference on AIDS suggests
that some infants (those who were infected with HIV perinatally
as opposed to those infected by transfusion) may be at high risk
of developing pneumocystis with well over 500 T- helper cells.3
A chart review of 38 infants in Los Angeles showed that 41
percent of the infants who acquired their HIV infection
perinatally were diagnosed with pneumocystis with a T-helper cell
count greater than 500. Of those who acquired their infection
perinatally and developed pneumocystis when they were less than
one year old, all had greater than 500 T-helper cells; in fact,
many had more than 1000 T-helper cells.
Although 93 percent of the infants who acquired their HIV
infection via transfusion and were diagnosed with pneumocystis
did have less than 500 T-helper cells, the official
recommendation for prophylaxis in some categories of infants, it
seems, should be reassessed.
Which Prophylaxis?
There are currently two different drugs for pneumocystis
prophylaxis in widespread use in the U. S: aerosolized
pentamidine, and Bactrim (also known as Septra, trimethoprim-
sulfamethoxazole, TMP-SMX, or cotrimoxazole). Both have been
officially recommended by the U. S. Department of Health and
Human Services in the Center for Disease Control's Morbidity and
Mortality Weekly Report, although neither was suggested to be the
better choice in this document.1 In addition to aerosolized
pentamidine and Bactrim, dapsone and dapsone plus pyrimethamine
are currently being used or considered by clinicians and patients
and are being tested in clinical trials. These drugs may have the
additional advantage of preventing toxoplasmosis.
Bactrim was the first successful pneumocystis prophylaxis
used in adults and children with cancer or organ transplants. It
was routinely used for this purpose in the late 1970s,4,5 before
AIDS was recognized. It was also the first drug used to prevent
pneumocystis in people with HIV infection, before the development
of aerosolized pentamidine. Even though it was shown to be very
effective in preventing pneumocystis,6 its toxicities (severe
rash, anemia, neutropenia, nausea, etc.) encouraged doctors,
researchers, and patients to search for alternative approaches.
By the late 1980s, the apparent effectiveness of aerosolized
pentamidine, and the relatively fewer and milder side effects
associated with it, made it the drug of choice among many
patients and clinicians. Aerosolized pentamidine was preferable
to some from a theoretical standpoint because delivering a toxic
drug directly to the site of action seemed safer than delivering
it to the whole body. This theory assumed, however, that
pneumocystis only causes disease in the lungs, which we now know
is not true.
Recently the following questions have been raised in an
attempt to understand which of these two regimens, aerosolized
pentamidine or Bactrim, may be best as a first choice for
prophylaxis: (1) Is one drug more effective than the other? (2)
Is there an increased incidence of pneumocystis infections in
organs other than the lung (extrapulmonary pneumocystis) in
patients using aerosolized pentamidine compared to those using
the systemic drug Bactrim? (3) Is there an increased incidence
in collapsed lungs (spontaneous pneumothorax) associated with the
use of aerosolized pentamidine? (4) Can Bactrim be used more
safely but just as effectively by using it less often? (5) Does
the use of aerosolized pentamidine make diagnosis of break-
through pneumocystis by chest x-ray, sputum, and bronchoalveolar
lavage (fluid collected during a bronchoscopy) more difficult
than does a systemic prophylaxis? (6) How do the issues of cost
and convenience fit into the risk/benefit equation? While
aerosolized pentamidine costs an average of $1,200 per year for
the drug alone, not including the significant costs associated
with administering the treatment, Bactrim (or generic
equivalents) may cost as little as $12 per year.
Aerosolized Pentamidine vs. Bactrim: Relative Safety and
Efficacy
The ideal way to determine which prophylaxis works best is
to compare the two directly in a large, controlled, prospective
clinical trial. Unfortunately, no such data is yet available.
An ongoing government-sponsored trial comparing these two drugs
is completing enrollment of patients at this time (ACTG 021).
According to David Hardy, M. D., one of the principal
investigators overseeing the study, the results are not expected
to be available in the next several months. The data will be
looked at periodically by a panel of experts (called a Data and
Safety Monitoring Board), however, and significant results will
be publicized if they are found before completion of the study.
Many physicians suspect that dapsone is comparably effective
to aerosolized pentamidine or Bactrim. Enrollment of a large
government-sponsored trial comparing these three drugs has been
completed (ACTG 081). This trial is scheduled to run until June
of 1992. The principal investigator, Sam Bozette, M. D., of the
University of California at San Diego, does not expect the trial
to be completed early because he does not expect to see a large
difference in the incidence of pneumocystis or adverse reactions
among the three groups.
Results of these two clinical trials should provide
important information about the relative efficacy of these three
approaches. In addition to the relative incidence of both
pulmonary and extrapulmonary pneumocystis, the incidence of
toxoplasmosis and bacterial infections among the different groups
will also be analyzed, with the expectation that the systemic
drugs may decrease the incidence of those infections as well.
Finally, the incidence of anemia will be compared among the
groups to see if the systemic drugs cause a significantly greater
incidence of anemia than does aerosolized pentamidine.
The only controlled trial of Bactrim for prophylaxis of
AIDS-related pneumocystis published in a peer-reviewed journal
to date is a Bactrim vs. no-treatment trial in patients with
Kaposi's sarcoma which was published in 1988.6 The treated group
(2 tablets a day plus 5 mg of leucovorin calcium) experienced no
pneumocystis, whereas 53 percent in the no-treatment group were
diagnosed with pneumocystis. Although effective, 50 percent of
those receiving Bactrim experienced toxicities (rash, nausea),
and 17 percent had to discontinue the prophylaxis.
Several uncontrolled studies were presented in San Francisco
at the Sixth International Conference on AIDS in June. Results
from a Danish trial of 122 people who had previously had at least
one episode of pneumocystis showed relapse in 8 of the 122
patients, who were using one double-strength tablet of Bactrim
daily, in a mean time of 13.1 months.7 In another study, a
retrospective chart review found no pneumocystis in patients
taking Bactrim once per day for 3, 6, 9, and 12 months.8 The
authors concluded that Bactrim was effective in preventing
pneumocystis when compared to an expected rate of 13 percent at 6
months and 24 percent at 12 months in patients not using a
prophylaxis. This study was small (21 patients at 12 months and
45 patients at 6 months) and uncontrolled, but strongly
suggestive of Bactrim's efficacy.
A recently published controlled, randomized, dose-comparison
study of aerosolized pentamidine initiated by the San Francisco
County Community Consortium (now the Community Consortium) in
1987 showed a significant decrease in the incidence of
pneumocystis in patients receiving 300 mg of aerosolized
pentamidine once a month as compared to those receiving 30 mg
every two weeks.9 According to the principal investigator of this
study, Gifford Leoung, M. D., of San Francisco General Hospital,
the use of 300 mg of aerosolized pentamidine once a month reduced
the incidence of pneumocystis to approximately 12 to 15 percent
of that previously seen in patients who used no prophylaxis.
This study, which was completed in December, 1988, was
instrumental in obtaining official FDA approval of aerosolized
pentamidine, making prophylaxis widely available to many people
with AIDS for the first time.
Clearly, both Bactrim and aerosolized pentamidine are
effective in decreasing the incidence of pneumocystis. But
neither is 100 percent safe and effective. Although aerosolized
pentamidine has become the most common prophylactic choice in
many areas of the U. S., researchers and clinicians have raised a
number of concerns about its use. We spoke with Sam Bozette, M.
D., the principal investigator on the U. S. government- sponsored
study of aerosolized pentamidine vs. Bactrim vs. Dapsone,
discussed above. Although data from that study is not yet
available, and Dr. Bozette has not seen any of it, he shared the
following thoughts with us based on clinical experience and his
understanding of the biology of the disease and the mechanisms of
the drugs available:
* He believes Bactrim should be the first line prophylaxis.
In his opinion, a systemic approach makes more sense than a local
approach. While acknowledging that aerosolized pentamidine is
effective, Dr. Bozette doubts the ability to deliver the drug to
all the areas in the lung where it is needed. He pointed out the
increased incidence of pneumocystis in the top portions of the
lungs in patients on aerosolized pentamidine prophylaxis.
* Dr. Bozette also pointed out the increased incidence of
extrapulmonary pneumocystis associated with the use of
aerosolized pentamidine, which he believes would be prevented
with the use of a systemic drug like Bactrim. Although several
small studies presented at the Sixth International Conference on
AIDS addressed the issue of extrapulmonary pneumocystis in
patients using aerosolized pentamidine, none compared the
incidence in those using aerosolized pentamidine with those using
a systemic drug like Bactrim or Dapsone.10 Therefore, while it
may seem likely that delivering the prophylactic treatment to the
whole body (as with Bactrim or dapsone) instead of only to the
lung (as with aerosolized pentamidine) would reduce the incidence
of extrapulmonary pneumocystis, we cannot be sure that this is,
in fact, the case.
* Dr. Bozette also noted, with the same reservation about a
lack of comparative data, the potential increased incidence of
spontaneous pneumothorax (collapsed lung) in patients on
aerosolized pentamidine. Clinicians and researchers disagree on
whether aerosolized pentamidine directly causes this problem. A
recent study found 12 pneumothoraces in 327 patients on
aerosolized pentamidine; of these, 83 percent required a chest
tube, and 6 of the 12 patients died. Seventy-five percent of
those with pneumothorax had evidence of active pneumocystis. The
researchers concluded that the pneumothorax was not directly
caused by use of aerosolized pentamidine, but rather "represents
a prophylaxis failure with a high mortality rate...[Their]
pathologic and clinical observations in patients receiving
aerosolized pentamidine with spontaneous pneumothorax indicate
that there are areas of the lung with inadequately controlled
infection with P. carinii ."11 The problem remains that there is
no data to compare the rate of pneumothorax in patients treated
with systemic drugs like Bactrim or dapsone to that in patients
using aerosolized pentamidine.
* Dr. Bozette also addressed the concern that the use of
aerosolized pentamidine might make diagnosis, and thus
management, of pneumocystis more difficult, as the number of
organisms would be decreased by the aerosolized pentamidine even
if they are not eliminated completely. At the Sixth
International Conference on AIDS in June, researcher Henry Masur,
M. D., reported that both sputum yield and the ability to
diagnose pneumocystis using bronchoalveolar lavage fluid are
decreased with the use of aerosolized pentamidine. However, a
study presented at the recent Thirtieth Interscience Conference
on Antimicrobial Agents and Chemotherapy (ICAAC, October 21-24,
1990, in Atlanta) found no difference in the ability to detect
the organism in sputum samples or bronchoalveolar lavage fluid of
patients using or not using aerosolized pentamidine.12 The
question remains open.
When asked which prophylactic treatment he would recommend
if a patient failed Bactrim, Dr. Bozette said that the following
factors should be taken into account: 1) if the patient does not
want to take more pills or is anemic or otherwise intolerant of
anti-retroviral therapy, he would recommend aerosolized
pentamidine; 2) if, however, the patient were allergic to
Bactrim, and did not have any of the other problems, he would
recommend dapsone as the second choice. Dr. Bozette emphasized
that the patient's preference is a very important variable in
this decision-making process.
Dr. Leoung, principal investigator for the San Francisco
aerosolized pentamidine study referred to above, suggested
several circumstances in which aerosolized pentamidine may be a
better first choice than one of the systemic drugs. Because
aerosolized pentamidine does not get into the circulation, it may
be a better choice in pregnant women, as there is some risk to
the fetus associated with the use of the systemic drugs. Also,
the government only pays for aerosolized pentamidine, because
Bactrim is not FDA-approved for pneumocystis prophylaxis.
Although Bactrim is much less expensive than aerosolized
pentamidine, this bit of bureaucratic logic may pose a problem
for some patients. Also, some patients may be taking other
medication which should not be combined with Bactrim. And for
some, the convenience of a monthly treatment is an important
factor.
If Bactrim, How Much? How Often?
Official US recommendations suggest that Bactrim should be
used twice a day, together with daily leucovorin. Most
physicians do not prescribe leucovorin, and many use Bactrim less
often than every day. The data on Bactrim use in pediatric
cancer patients demonstrated that there was no difference in its
effectiveness when used daily as opposed to three times a
week.4,13 In AIDS TREATMENT NEWS issue #106, Dr. Marcus Conant
reported on the successful use of Bactrim two times a day, twice
a week by Cooper, from Australia. A study published but not
presented at the Sixth International Conference on AIDS reported
a decrease in the incidence of moderate and severe side effects
(rash, nausea) with one tablet per day as opposed to two tablets
every day or two tablets three times a week; this study included
almost 200 participants.14
Four studies presented at the recent ICAAC conference
suggest that one tablet taken three times a week is safe and
effective in preventing pneumocystis. Two of these studies were
retrospective chart reviews which looked at the incidence of
pneumocystis and side effects in patients taking one tablet
thrice weekly. The first study15 found no pneumocystis in 115
patients followed for an average of 20 months (range 3-46); the
second16 found one case of pneumocystis in 64 patients followed
for approximately 8 months (primary prophylaxis) or over 9 months
(secondary prophylaxis). Twenty-nine percent of the people in
the first study experienced side effects (rash, nausea, vomit,
rare fever) and 13 percent discontinued therapy; only three of
the 64 patients discontinued therapy in the second study.
A third study17 compared, via retrospective chart review,
daily (18 patients) vs. thrice weekly (35 patients) Bactrim.
There was one case of pneumocystis. There was a higher incidence
of anemia in the thrice weekly treatment group but higher
incidences of neutropenia, nausea, and vomiting in the daily
treatment group. The incidence of toxicity which required
discontinuation of Bactrim was approximately equal in the two
groups.
The fourth study, also a chart review,18 demonstrated a
lower incidence of pneumocystis in patients on thrice weekly
Bactrim than those on aerosolized pentamidine (7 percent vs. 20
percent with a total of almost 100 patients). All of these
studies were relatively small chart reviews, as opposed to large,
controlled studies, and thus provide strong suggestive, though
not conclusive, data about the effectiveness of one Bactrim
tablet three times per week.
Dapsone With or Without Pyrimethamine
The general consensus in the medical community is that there
is not enough data to determine the efficacy of dapsone in
preventing pneumocystis, but that it is expected to be
approximately as effective as Bactrim. The most serious toxicity
associated with dapsone is hemolytic anemia; patients should have
their G6PD (glucose-6-phosphate dehydrogenase, an enzyme) levels
tested before taking dapsone because the anemia can be severe in
patients with a G6PD deficiency.
A study with almost 200 people presented at the June, 1990,
Sixth International Conference on AIDS found a statistically
non-significant difference in the incidence of pneumocystis and
the length of time to infection between a group treated with
aerosolized pentamidine (100 mg every two weeks) and dapsone (100
mg twice a week). Although not statistically significant, the
dapsone group did have a slightly lower incidence and a slightly
longer disease-free interval.19
Dapsone was compared with Bactrim in a study presented at
the Fifth International Conference on AIDS in Montreal;20 two out
of 173 in the dapsone group vs. none of 48 in the Bactrim group
developed pneumocystis. Only 10 percent of the dapsone group
experienced adverse reactions requiring termination of therapy,
as opposed to 38 percent of the Bactrim group. Treatment was
studied for an average of eight to nine months. Importantly,
patients who were allergic to one drug generally tolerated the
other.
Two short, small studies presented at the Sixth International
Conference on AIDS looked at the safety and effectiveness of
dapsone plus pyrimethamine.21 Anemia was the primary toxicity and
was usually tolerable. Nausea, vomiting, and rash also occurred
in a small number of participants. No pneumocystis developed in
20 patients with a mean follow up of 6.5 months (range 4-16
months).
Preventing Toxoplasmosis Too?
Dapsone may have the additional advantage of preventing
toxoplasmosis, especially when used with pyrimethamine, one of
the standard treatments for this disease. When asked by a doctor
in the audience at the Sixth International Conference on AIDS if
he believed Bactrim could prevent toxoplasmosis, Dr. Henry Masur
from the National Institutes of Health replied that Bactrim was
not effective against toxoplasmosis in animals or in the test
tube, but that he expected that dapsone plus pyrimethamine or the
new Burroughs-Wellcome drug 566C80 (see below) would have broad
anti-parasitic activity against it, as well as against
pneumocystis. Another combination he suggested for further study
is dapsone plus trimethoprim for those who are allergic to the
sulfamethoxazole in Bactrim. (Note that some physicians and
researchers do expect that Bactrim may also prevent
toxoplasmosis; this question is being addressed in the two
government-sponsored trials discussed above.)
A Note on Fansidar
Fansidar (sulfadoxine-pyrimethamine) continues to be studied
in some European countries, but has largely fallen out of favor
as a pneumocystis prophylaxis in the U. S. because of its rare
but potentially fatal side effects. It has been associated with
a severe allergic reaction called Steven's-Johnson syndrome. For
more information, consult the Physicians' Desk Reference.
Experimental Prophylaxis
A Promising New Drug: 566C80
566C80 is a member of an anti-parasitic class of drugs
called naphthoquinones. Unlike the treatments now in use, it may
be able to destroy the cysts in which pneumocystis lives in a
latent state in the human body. It may also be useful in the
prevention and treatment of other parasitic opportunistic
infections in AIDS, such as toxoplasmosis and cryptosporidiosis.
The drug has been demonstrated by researchers at Burroughs-
Wellcome and St Jude's Children's Research Hospital in Memphis,
Tennessee, to be effective in test-tube and animal studies.22,23
An early human study24 examined the safety of increasing
doses of 566C80 in six groups of four people each. The only
adverse reaction was a rash in one person at the highest dose;
the rash cleared after the drug was discontinued. More studies
are currently underway or being designed to examine the safety
and efficacy of this drug in the treatment and prophylaxis of
pneumocystis. Those who are interested in more information about
these studies can call 800/TRIALS-A for eligibility information
and referrals to the appropriate study sites.
For a more complete discussion of the research on this
compound, see Treatment Issues, volume 4, number 7 (published by
Gay Men's Health Crisis, Department of Medical Information, 129
West 20th Street, New York, NY 10011).
Other Experimental Approaches
The pneumocystis carinii organism which causes pneumocystis
has characteristics of both protozoa and fungi. Several
preliminary animal studies presented at the ICAAC conference
examined the effectiveness of a group of compounds that are
believed to be effective against the fungal properties of the
organism. Researchers from Merck Sharp and Dohme and Eli Lilly
presented data on beta-1,3-glucan synthase inhibitors. Beta
glucan is a structural component of many fungal cell walls.
The most compelling data25 compared the effects of one of
these drugs, L671,329, with Bactrim and pentamidine in treating
rats with pneumocystis. More than 98 percent of the cysts were
eliminated in those rats treated with L671,329 after 4 days;
those rats treated with the other two drugs showed no significant
differences in cyst load after 4 days as compared to control
rats. A second beta-1,3-glucan synthase inhibitor, L687,781, was
shown to be less potent, but effective, in eliminating cysts
(greater than 83 percent after five days of treatment).26
L671,329 was also reported to be an effective prophylaxis in the
immunosuppressed rats.
A third study27 evaluated cilofungin and echinocandin B in
rats and found that the cysts in the lungs were swollen and that
the nuclei indicated cell death. The authors of this study
suggested that these compounds were effective in both treatment
and prophylaxis.
We expect continuing improvement in pneumocystis prevention
and treatment, as more information becomes available through
pre-clinical research (laboratory and animal studies) and
clinical trials.
References
1. U. S. Department of Health and Human Services, Public Health
Service. Guidelines for prophylaxis against Pneumocystis carinii
pneumonia for persons infected with human immunodeficiency virus.
Morbidity and Mortality Weekly Report (MMWR) Recommendations and
Reports. June 16, 1989; volume 38, number S-5.
2. Pneumocystis prophylaxis survey results reported in The
Synopsis of the Community Consortium. July 3, 1990; volume 3,
number 7. [The Community Consortium is a group of health-care
providers who are involved in community-based clinical research.
The majority of these providers practice in the San Francisco Bay
Area.]
3. Kovacs A, Church J, Mascola L, and others. CD4 counts as
predictors of Pneumocystis carinii pneumonia in infants and
children with HIV infection [abstract F. B. 24]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
4. Hughes WT, Kuhn S, Chaudhary S, and others. Successful
chemoprophylaxis for Pneumocystis carinii pneumonia. The New
England Journal of Medicine. December 29, 1977; volume 297,
pages 1419-1426.
5. Harris RE, McCallister JA, Allen SA, Barton AS, and Baehner
RL. Prevention of pneumocystis pneumonia. Use of continuous
sulfamethoxazole-trimethoprim therapy. American Journal of
Diseases of Children. 1980; volume 134, number 1, pages 35-38.
6. Fischl M A, Dickinson G M, and La Voie L. Safety and efficacy
of sulfamethoxazole and trimethoprim chemoprophylaxis for
Pneumocystis carinii pneumonia. Journal of the American Medical
Association. February 26, 1988; volume 259, pages 1185-1189.
7. Nielsen T L, Jensen B N, Nelsing S and others.
Sulfamethoxazole/trimethoprim as secondary prophylaxis against
Pneumocystis carinii pneumonia [abstract Th.B. 412]. Sixth
International Conference on AIDS, San Francisco, June 20- 24,
1990.
8. Kelly J, Keyes C, Marte C, Wolbert J, and Chieffe R. Once
daily trimethoprim/sulfamethoxazole as prophylaxis for
Pneumocystis carinii pneumonia [abstract Th.B. 413]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
9. Leoung GS, Feigal DW, Montgomery AB, and others. Aerosolized
pentamidine for prophylaxis against Pneumocystis carinii
pneumonia. The New England Journal of Medicine. September 20,
1990; volume 323, number 12.
10. McCabe R and Edelstein H. Atypical Pneumocystis carinii
pneumonia in patients receiving inhaled pentamidine prophylaxis
[abstract 426]. Also Denis M, Guidet B, and Lebas J. Clinical
data of disseminated Pneumocystis carinii infection in 6 AIDS
patients receiving secondary prophylaxis with aerosolized
pentamidine [abstract 427]. Also Noskin G, Murphy R L, Finn W G,
and Timins M. Extrapulmonary Pneumocystis carinii in patients
receiving aerosolized Pentamidine [abstract 428]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
11. Newsome GS, Ward DJ, and Pierce PF. Spontaneous pneumo-
thorax in patients with acquired immunodeficiency syndrome
treated with prophylactic aerosolized pentamidine. Archives of
Internal Medicine. October 1990; volume 150, pages 2167-2168.
12. Geaghan S, Fahey J, McGinty E, and others. Impact of
prophylactic aerosolized pentamidine on the laboratory diagnosis
of Pneumocystis carinii pneumonia [abstract 850]. 30th
Interscience Conference on Antimicrobial Agents and Chemotherapy,
Atlanta, October 21-24, 1990.
13. Hughes, WT and others. Successful intermittent
chemoprophylaxis for Pneumocystis carinii pneumonia. New England
Journal of Medicine. 1987; volume 316, pages 1627-1632.
14. Wolbert J, Keyes C, Chieffe R, Marte C, Kelly J, and Holzman
R S. Side effects of prophylactic trimethoprim/sulfamethoxazole
are diminished with once daily dosing [abstract 2086]. Sixth
International Conference on AIDS, San Francisco, June 20-24,
1990.
15. Lariviere M and Ruskin J. Low dose
trimethoprim/sulfamethoxazole prevents Pneumocystis carinii
pneumonia [abstract 8]. 30th Interscience Conference on
Antimicrobial Agents and Chemotherapy, Atlanta, October 21-24,
1990.
16. Stein D
source: AIDS Treatment News
