Download Reply to Chalmers and Hill To the Editor—We thank Chalmers and

Reply to Chalmers and Hill
To the Editor—We thank Chalmers and
Hill [1] for their comments. Although we
agree that simplicity is certainly desirable
for pneumonia severity assessment tools,
this is not necessarily practical. Patients
who require intensive respiratory or vasopressor support have a variety of indications for receiving such care. In the patient databases used in our study [2],
simpler severity assessment tools, such as
CURB-65 (or variations of it, such as
CRB-65, CURB, or CRB), resulted in either high sensitivity or high specificity but
not both. Thus, these simple tools will,
depending on the chosen cutoff score,
identify too many patients as having severe
pneumonia or, alternatively, identify only
a minority of patients with severe disease.
Because neither of these options is clinically useful, we developed our slightly
more complex tool to achieve a better balance of sensitivity and specificity.
Acknowledgments
Potential conflicts of interest. All authors: no
conflicts.
Patrick G. P. Charles,1,2 Rory Wolfe,3
and M. Lindsay Grayson1,2,3
1
Department of Infectious Diseases, Austin Health,
Heidelberg, 2Department of Medicine, University of
Melbourne, Parkville, and 3Department of
Epidemiology and Preventive Medicine, Monash
University, Clayton, Victoria, Australia
References
1. Chalmers JD, Hill TA. A powerful new severity
score for community-acquired pneumonia but
will anyone use it? Clin Infect Dis 2008; 47:1363
(in this issue).
2. Charles PGP, Wolfe R, Whitby M, et al.
SMART-COP: a tool for predicting the need
for intensive respiratory or vasopressor support
in community-acquired pneumonia. Clin Infect Dis 2008; 47:375–84.
Reprints or correspondence: Dr. Patrick G. P. Charles, Dept.
of Infectious Diseases, Austin Health, PO Box 5555, Heidelberg VIC 3084, Australia ([email protected]).
Clinical Infectious Diseases 2008; 47:1364
2008 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2008/4710-0024$15.00
DOI: 10.1086/592748
Use of a Serum (1r3)-b-dGlucan Assay for Diagnosis
and Follow-Up of
Pneumocystis jiroveci
Pneumonia
To the Editor—We read with great interest the letter by Pisculli and Sax [1]
about the diagnostic usefulness of the
(1r3)-b-d-glucan (BG) assay for the diagnosis of HIV-related Pneumocystis jiroveci pneumonia (PJP) in 3 patients with
negative results of microscopic examination of respiratory samples. Here, we report the prospective observation of BG
reactivity (Fungitell; Associates of Cape
Cod) in serum samples from 3 HIV-infected patients with positive results of immunofluorescence tests of respiratory secretions and 2 immunocompromised patients with negative results of immunofluorescence and positive results of real-time
PCR of bronchoalveolar lavage specimens
(table 1) [2].
Accurate and rapid diagnosis of PJP
may be difficult, because of nonspecific
symptoms and signs and because it requires positive microscopic examination
of respiratory secretion samples. However,
negative results of microscopy of respiratory secretions do not exclude the diagnosis of PJP, because the sensitivity is
variable and, in many instances, is !50%.
PCR has been shown to have greater sensitivity and specificity in evaluating induced sputum and bronchoalveolar lavage
fluid specimens, but the interpretation of
results may be conflicting, because asymptomatic P. jiroveci carriage is possible, in
both immunocompetent and immunocompromised individuals [3].
There are a number of commercially
available methods for the detection of BG
through use of different methodologies,
cut-off values, and sensitivity. The chromogenic BG test (Fungitell) has been approved by the US Food and Drug Administration as an adjunct for the diagnosis of invasive fungal disease, although
the initial validation of BG testing in
United States did not include patients with
PJP [4].
Currently, the information about the
1364 • CID 2008:47 (15 November) • CORRESPONDENCE
diagnostic potential of the Fungitell BG
test for the diagnosis of PJP is scarce; to
our knowledge, there have been only 2
published reports [1, 5] and a poster presented at a scientific meeting [6]. The kinetics of BG release from the infected sites
and of circulation of BG in blood, as well
as clearance of BG, are poorly understood.
The kinetics shown relative to patients 1
and 4 (table 1) suggest that decreasing levels of BG correspond with a favorable response to treatment, whereas increasing
levels are associated with treatment failure
(as for patient 3). The conditions of patients 2 and 5 deteriorated rapidly, and no
serum samples were obtained for followup. Decreasing BG values after treatment
with trimethoprim-sulfamethoxazole have
also been described in several patients with
confirmed PJP [5, 6]. These preliminary
results suggest that monitoring BG antigenemia would also be a valuable tool in
predicting therapeutic outcome in patients
with PJP, although more clinical and mycological experience is warranted.
It is important to stress that none of
our patients had received PJP prophylaxis,
for various reasons: (1) because PJP led to
the diagnosis of HIV infection, (2) because
of noncompliance with HIV treatment,
and (3) because of known patient allergy
to trimethoprim-sulfamethoxazole.
We concur with Pisculli and Sax [1] that
the BG assay is a noninvasive serological
marker that can be used as an adjunct for
the diagnosis of PJP, particularly in patients with severe disease, profound
thrombocytopenia, or pulmonary condition so poor that the use of fiberoptic
bronchoscopy with bronchoalveolar lavage specimens is often precluded because
of the trauma that may be caused by the
procedure.
Acknowledgments
We thank Dr. Malcolm A. Finkelman for critical
reading of the manuscript.
Financial support. Fondo de Investigación
Sanitaria, Instituto de Salud Carlos III (PI070107
to A.d.P., PI070134 to M.S.C., and PI070376 to
J.P.), and Pfizer Spain (to A.d.P.).
Potential conflicts of interest. All authors: no
conflicts.
298
670
Lactate dehydrogenase level, U/L
794
Yes
M
45
Patient
745
No
No
No
356,253
28
Known advanced HIV disease,
noncompliant with HIV treatment, 4 months of dyspnea,
fever, coughing, constitutional
syndrome
3
Cured
TMP-SMX
W 1, 402; W 4, 217; W 6, 59
525
BAL (IFA)
Died
TMP-SMX, pentamidine
Not available
231
Induced sputum (IFA)
Died
TMP-SMX
W 2, 9198
4409
BAL (IFA)
b
a
Cutoff value, 1230 U/L.
Cutoff value, ⭓80 pg/mL.
NOTE. BAL, bronchoalveolar lavage; IFA, immunofluorescence assay; TMP-SMX, trimethoprim-sulfamethoxazole; W, week.
Clinical outcome
Treatment
b-d-Glucan level during treatment, pg/mL
Initial b-d-glucan level, pg/mL
b
Positive type of respiratory sample
(technique used)
Chest radiograph type and finding(s)
b
No
Cytomegalovirus coinfection
No
No
Not available
116
Known advanced HIV disease,
noncompliant with HIV treatment, 3 weeks of dyspnea,
high-grade fever, coughing,
expectoration, constitutional
syndrome
F
35
2
300
Yes
Yes
Yes
Not applicable
217
Renal transplant in previous 2 months, dyspnea,
low-grade fever, dry coughing
M
77
4
746
No
Yes
Yes
Not applicable
Not available
Advanced follicular lymphoma for
2 years, severe dyspnea,
high-grade fever
F
76
5
Cured
Pentamidine
W 2, 410; W 4, 193; W 6, 94
2563
BAL (RT-PCR)
Died
TMP-SMX
Not available
599
BAL (RT-PCR)
CT, bilateral ground-glass opacities Radiography, bilateral consolidation Radiography, bilateral consolidation CT, bilateral ground-glass opacities and pleural effusion CT, bilateral ground-glass opacities
No
a
No
Corticosteroids
79,432
Chemotherapy or immunosuppressive drugs
Plasma HIV RNA load, copies/mL
Absolute CD4 cell count, cells/mm3
New diagnosis of HIV infection, 4
weeks of dyspnea, high-grade
fever, dry coughing, weight
loss
M
Sex
Clinical syndrome
44
1
Age, years
Variable
Table 1. Demographic and clinical findings for 5 patients with Pneumocystis jiroveci pneumonia.
Marı́a Soledad Cuétara,1 Almudena Alhambra,2
Fernando Chaves,2 Marı́a Dolores Moragues,3
José Pontón,4 and Amalia del Palacio2
1
Servicios de Microbiologı́a, Hospital Severo Ochoa,
and 2Hospital Universitario 12 de Octubre, Madrid,
and Departamentos de 3Enfermerı́a I and
4
Inmunologı́a, Microbiologı́a y Parasitologı́a,
Facultad de Medicina y Odontologı́a, Universidad
del Paı́s Vasco, Bilbao, Vizcaya, Spain
References
1. Pisculli ML, Sax PE. Use of a serum b-glucan
assay for diagnosis of HIV-related Pneumocystis
jiroveci pneumonia in patients with negative
microscopic examination results. Clin Infect
Dis 2008; 46:1928–9.
2. Larsen HH, Masur H, Kovacs JA, et al. Development and evaluation of a quantitative, touchdown, real-time PCR assay for diagnosing
Pneumocystis carinii pneumonia. J Clin Microbiol 2002; 40:490–4.
3. Morris A, Lundgren JD, Masur H, et al. Current
epidemiology of Pneumocystis pneumonia.
Emerg Infect Dis 2004; 10:1713–20.
4. Ostrosky-Zeichner L, Alexander BD, Kert DH,
et al. Multicenter clinical evaluation of the
(1r3) b-D-glucan assay as an aid to diagnosis
of fungal infections in humans. Clin Infect Dis
2005; 41:654–9.
5. Marty FM, Koo S, Bryar J, Baden LR. (1r3)bd-Glucan assay positivity in patients with Pneumocystis (carinii) jiroveci pneumonia. Ann Intern Med 2007; 147:70–2.
6. Marty FM, Koo S, Bryar J, Baden LR. (1r3)b-d-Glucan assay positivity in oncologic patients with Pneumocystis jiroveci pneumonia
(PCP) [abstract M-1606]. In: Program and abstracts of the 46th Interscience Conference on
Antimicrobial Agents and Chemotherapy (San
Francisco). Washington, DC: American Society
for Microbiology, 2006:425.
Reprints or correspondence: Dr. José Pontón, Departamento
de Inmunologı́a, Microbiologı́a y Parasitologı́a, Facultad de
Medicina y Odontologı́a, Universidad del Paı́s Vasco, Apartado
699, 48080 Bilbao, Spain ([email protected]).
Clinical Infectious Diseases 2008; 47:1364–6
2008 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2008/4710-0025$15.00
DOI: 10.1086/592753
Routine HIV Testing in Jails
Is Critical for the Early
Diagnosis of HIV Infection
in Men
Keruly et al. [1] recently published a discouraging article that demonstrated that
the mean CD4 cell count of persons who
presented to the Moore Clinic at Johns
Hopkins University (Baltimore, MD) decreased from 371 cells/mm3 during 1990–
1994 to 276 cells/mm3 during 2003–2006.
Given remarkable advances in HIV treatment during this period, it is disheartening
to learn that the immune status of persons
with newly diagnosed HIV infection is
worse now than it was in the mid-1990s.
Late presentation for care was associated
with black race and male sex. The authors
emphasized the need for development of
new HIV testing and referral strategies that
would facilitate patients entering care
earlier.
The Centers for Disease Control and
Prevention recently recommended routine
opt-out HIV screening in health care settings [2]. This recommendation is laudable but may miss many men aged 18–45
years. A considerable number of men in
this age group do not receive routine medical care. This is particularly true for innercity black men, who have an increased
likelihood of being poor and less educated
and who often lack health insurance. Black
men are also disproportionately incarcerated and afflicted by HIV infection, compared with men of other races. In 2006,
4.8% of black men were in custody; the
highest rates of incarceration were among
black men aged 25–29 years [3]. At the
end of 2006, 47% of persons living with
HIV/AIDS were black [4]. The correctional system represents an important
venue for delivering HIV services (including testing, treatment, and linkage to community HIV care) to minority men,
because of the high frequency of incarceration, increased rates of HIV infection,
and marginalization from the health care
system in this population.
Until recently, routine HIV testing was
not performed in the Baltimore City jail
system. However, in May 2008, rapid HIV
testing began to be performed as part of
the medical intake for persons processed
in the jail. This testing intervention has
the potential to significantly increase the
number of diagnoses of HIV infection
among Baltimore residents, thus facilitating earlier entry into care for persons who
are found to be HIV infected. The expansion of testing is accompanied by referral
mechanisms for HIV care. The Baltimore
1366 • CID 2008:47 (15 November) • CORRESPONDENCE
City jail system and its collaborators
should be commended for this important
response. The use of rapid HIV testing is
particularly important, because it will enable efficient delivery of test results, and
jail incarceration is often brief and unpredictable. It is critical that individuals
have the opportunity to receive their test
results quickly, such that confirmatory
testing and linkage to care can be initiated
for persons with reactive rapid test results.
Expansion of routine HIV testing
within jails is occurring in a few cities
across the United States, although broader
implementation has yet to occur. In this
time of limited resources and shrinking
budgets, interventions with maximum
public health impact need to be prioritized, and the Baltimore City jail has taken
an important step in addressing the city’s
epidemic of HIV infection. Other jails
around the nation should follow suit.
Acknowledgments
Potential conflicts of interest. T.P.F. and
C.G.B.: no conflicts.
Timothy P. Flanigan and Curt G. Beckwith
Alpert Medical School of Brown University,
Providence, Rhode Island
References
1. Keruly JC, Moore RD. Immune status at presentation to care did not improve among antiretroviral-naive persons from 1990–2006. Clin
Infect Dis 2007; 45:1369–74.
2. Centers for Disease Control and Prevention.
Revised recommendations for HIV testing of
adults, adolescents, and pregnant women in
health-care settings. MMWR Morb Mortal
Wkly Rep 2006; 55(RR-14):1–17.
3. Sabol WJ, Minton TD, Harrison PM. Prison
and jail inmates at midyear, 2006. Document
NCJ 21675. Washington, DC: US Department
of Justice, 2007.
4. Centers for Disease Control and Prevention.
Cases of HIV infection and AIDS in the United
States and dependent areas, 2006. Available
at:
http://www.cdc.gov/HIV/topics/
surveillance/basic.htm. Accessed 25 July 2008.
Reprints or correspondence: Dr. Curt G. Beckwith, Div. of
Infectious Diseases, The Miriam Hospital, 164 Summit Ave.,
Providence, RI 02906 ([email protected]).
Clinical Infectious Diseases 2008; 47:1366
2008 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2008/4710-0026$15.00
DOI: 10.1086/592754