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KEY WORDS: Nocardia spp., pulmonary nocardiosis, relative risk, trimethoprim/sulfamethoxazole, linezolid.
* Author to whom correspondence should be addressed. E-mail: sakina.fatima@jsmu.edu.pk
Latin American Journal of Pharmacy
(formerly Acta Farmacéutica Bonaerense)
Lat. Am. J. Pharm. 40 (10): 2420-4 (2021)
Received: June 2, 2021
Revised: August 9, 2021
Accepted: August 10, 2021
Antimicrobial Susceptibility to Nocardia Infection from 2015-2018 in a
Tertiary Care Hospital Diagnostic Laboratory from Karachi, Pakistan
Sakina FATIMA 1*, Subia JAMIL 2, Sumira ISHAQ 3,
Shahnaz USMAN 4, Humaira ANSER 5& Wafa OWAIS 6
1Department of Pharmaceutics, Institute of Pharmaceutical Sciences,
Jinnah Sindh Medical University, Karachi, Pakistan.
2Department of Pharmacology, 6Department of Pharmaceutics, Faculty of Pharmacy,
Jinnah University for Women, Karachi, Pakistan.
3Department of Pharmacognosy, 5Department of Pharmacology,
Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.
4Department of Pharmaceutics, RAK College of Pharmaceutical Sciences,
RAK Medical and Health Sciences University, Ras Al Khaimah, UAE
SUMMARY. The objective of this study was to investigate nocardiosis with focus on the incidence of pul-
monary nocardiosis and the role of antibiotics. A retrospective study was performed during the period of
January 2015 to June 2018. The collected data was analyzed statistically by using Pearson’s Chi square
test at the significance level p< 0.05. A total of n = 56 cases of nocardiosis were reported during the cited
period. The occurrence of pulmonary nocardiosis was 80.4% (45/56); 38 (38/45 = 84.45 %) were male gen-
der (OR = 3.102; 95% CI = 0.714-13.48; RR = 1.327; p0.130) and 37 (82.22 %) were patients from ICU
(OR = 2.643; 95% CI = 0.622-11.230; RR = 1.292; p0.172), both were found statistically non-significant.
On the other hand, in year 2018, pulmonary nocardiosis (OR = 8; 95% CI = 0.943-64.864; RR = 4.889; p=
0.029) was found with significant association with genders. Trimethoprim/sulfamethoxazole, amikacin,
linezolid, vancomycin and tetracycline were effective choices of antibiotics. It was concluded that the pul-
monary nocardiosis is more significant in male and the rate of cases were increased progressively during
2015-2018 in Karachi, Pakistan.
RESUMEN. El objetivo del estudio fue investigar la nocardiosis con especial atención a la incidencia de nocar-
diosis pulmonar y el papel de los antibióticos.Se realizó un estudio etrospectivo durante el período de enero de
2015 a junio de 2018. Los datos recopilados se analizaron estadísticamente mediante la prueba de Chi cuadrado
de Pearson en el nivel de significancia p< 0.05. Se notificaron un total de n = 56 casos de nocardiosis durante el
período citado. La ocurrencia de nocardiosis pulmonar fue del 80,4% (45/56); 38 (38/45 = 84,45%) eran del sexo
masculino (OR = 3,102; IC del 95% = 0,714-13,48; RR = 1,327; p0,130) y 37 (82,22%) eran pacientes de UCI
(OR = 2,643; IC del 95% = 0,622-11,230; RR = 1,292; p= 0,172), ambos se encontraron estadísticamente no sig-
nificativos. Por otro lado, en el año 2018 se encontró nocardiosis pulmonar (OR = 8; IC 95% = 0,943-64,864; RR
= 4,889; p= 0,029) con asociación significativa con los géneros. Trimetoprim/sulfametoxazol, amikacina, line-
zolid, vancomicina y tetraciclina fueron opciones eficaces de antibióticos. Se concluyó que la nocardiosis pulmo-
nar es más significativa en varones y la tasa de casos se incrementó progresivamente durante 2015-2018 en Kara-
chi, Pakistán.
INTRODUCTION
Nocardia is an opportunistic pathogen but
can infect immune-compromised patients 1. The
pathogen is an aerobic prokaryotic, gram-posi-
tive bacteria having a filamentous structure,
mostly found in soil, dust, sand and stagnant
waters 2, that permit the pathogen to endure in
the hospital environment and thus to infect the
susceptible hosts 3-5.
The review of literature showed that more
than 85 species of Nocardia species are identi-
fied and around 25 species are related with hu-
man infections 6,7. Pulmonary nocardiosis is the
most common form of infection, however, the
incidences are rare but out of 500-1000 Nocar-
dia spp. cases, 85% were serious pulmonary
systemic infection in USA 8. Nocardia spp.
caused pulmonary infections may be acute or
ISSN 0326 2383 (printed ed.)
ISSN 2362-3853 (on line ed.)
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chronic. In some developing countries where
chronic lung diseases are prevalent nocardiosis
is often confused with chronic lung diseases
such as tuberculosis 9,10. Recent report on pul-
monary nocardiosis indicated that major risk
factor was immune-compromising and pul-
monary co-morbidities in elderly males 11. It was
also reported that the cases were rare in China
but susceptible with linezolid, imipenem and
amikacin 12.
The study regarding pulmonary nocardiosis
defined that its prevalence is low in Pakistan as
total of 41 cases were reported between 2000-
2010 13 and 70 cases were during 1990-2005 14.
In simple words we can say that only few stud-
ies were conducted on pulmonary nocardiosis
in Pakistan, the new one revealed 41 cases dur-
ing 2014-2016 15. The less number of cases
could be due to the lack of awareness or low
socioeconomic condition of majority of popula-
tion. In addition, the people do not approach
doctors in time and ignore the presenting symp-
toms that lead to serious complications of dis-
ease. Self-medication and treatment from quakes
also contribute in changing the real aspect of
the studies. The present study was aimed to in-
vestigate the reported cases of nocardiosis in
hospitalized patient, but with an especial focus
on pulmonary nocardiosis along with effective
antibiotic choices. The study also focused on in-
cidence of pulmonary nocardiosis during the
years 2015-2018 in Karachi, Pakistan.
MATERIAL AND METHODS
Study layout
A retrospective cross-sectional study was de-
signed to investigate the frequency of Nocardia
infection in patients admitted in a low socio-eco-
nomic tertiary care hospital setup. The data of pa-
tients were collected based on a retrospective re-
view of cases from January 2015-June 2018 from
Karachi, Pakistan. The Nocardia species were iso-
lated from clinical specimen of sputum, broncho-
alveolar lavage and tracheal aspirates.
Inclusion criteria
All patients were eligible to be included in
the study if they were treated with documented
evidence of Nocardia infection such as symp-
toms and signs, culture reports along-with medi-
cal record.
Data collection
The data of patients were stratified in to two
groups i.e., pulmonary Nocardiosis and Non-
pulmonary nocardiosis. Pulmonary nocardiosis
group included patients with symptoms of dysp-
nea, cough and sputum production.
Phenotypic identification
The isolates were investigated at genus level
for phenotypic identification of aerobic actino-
mycetes according to UK Standards for Microbi-
ological Investigations (SMIs). On microscopy
Nocardia isolates were resulted as partial acid-
fast, Gram-positive, branching rods and aerobic
growth of chalky white, catalase positive
colonies.
Antimicrobial susceptibilities
On availability of medical records, the preva-
lence of pulmonary Nocardiosis was determined
along-with antimicrobial treatment choices ef-
fective against Nocardia infection in patients ad-
mitted in various wards. The study focused on
antimicrobial susceptibilities of various antibi-
otics such as ampicillin (AMP), amoxicilin/clavu-
lanic acid (AMC), ceftriaxone (CRO), cefotaxime
(CTX), cefepime (CFM), pipracillin/tazobactam
(PTZ), amikacin (AMK), tobramycin (TOB),
trimethoprim/sulfamethoxazole (SXT), doxycy-
cline (DOX), tetracycline (TCN), clarithromycin
(CLN), vancomycin (V), ciprofloxacin (CIP), lev-
ofloxacin (LEV), imipenem (IMP) and linezolid
(LZD). The antimicrobial susceptibilities were
carried out by interpretive breakpoints of mini-
mum inhibitory concentration (MIC) under rec-
ommended CLSI guidelines 16.
Statistical analysis
Pearson’s Chi square or Fischer’s exact test
were used to analyze the statistical association
between pulmonary nocardiosis with gender,
wards and number of cases reported in each
year. To analyze Odds ratio and confidence in-
terval (CI) were calculated at 0.05 level of signif-
icance using SPSS version 20.
RESULTS
Frequency of Nocardia infection
Total 56 patients were identified with one or
more cultures positive for Nocardia during Jan-
uary 2015-June 2018; 6 from 2015, 4 from 2016,
25 from 2017 and 21 from 2018. The index of
years has described an increasing number of
cases over time. This increase was, may be due
to an increase in the population, or due to in-
crease number of patients with compromised
immune systems. In total 56 patients, male pre-
ponderance was 80.4% (n = 45) and 19.6% (n =
Latin American Journal of Pharmacy - 40 (10): 2420-4 (2021)
2422
FATIMA S., JAMIL S., ISHAQ S., USMAN S., ANSER H. & OWAIS W.
11) were females. The outcomes of various
wards analysis indicated that the Nocardia spp.
were reported highest from intensive and critical
care units i.e. n = 44, whereas in internal
medicine n = 6; n = 2 in nephrology and pedi-
atrics, and n =1 in each oncology and operation
theater.
Pulmonary nocardiosis
Of 56 cases of Nocardiosis, 80.4% (n = 45)
were pulmonary nocardiosis with various speci-
mens of sputum, bronchoalveolar lavage, endo-
tracheal Aspirate and Non pulmonary specimens
were abscess, pleural fluids and blood i.e., 11
out of 56 cases (Table 1). Pulmonary nocardio-
sis was found statistically non-significant with
gender and wards; however, male gender (OR =
3.102; 95% CI = 0.714-13.48; RR = 1.327; p
0.130) and patients from ICU (OR = 2.643; 95%
CI = 0.622-11.230; RR = 1.292; p0.172) were
dominant with 38 and 37 cases of pulmonary
nocardiosis respectively (Table 2). The number
of cases reported each year were found to be
statistically non-significant i.e., p > 0.05, whereas
Specimen source n (%)
Pulmonary 45 (80)
Sputum 37 (66)
Bronchoalveolar lavage 4(7)
Tracheal aspirates 4 (7)
Non Pulmonary 11(20)
Abscess 7 (12.5)
Pleural fluids 3 (5.35)
Blood 1 (1.78)
Table 1. Specimen distribution of Nocardia spp. (n =
56).
Pulmonary Non Pulmonary p-value odds ratio (95% C.I) RR
Gender Male 38 7 0.130 3.102 (0.714-13.48) 1.327
Female 7 4
Wards ICU 37 8 0.172 2.643 (0.622-11.230) 1.292
Other wards 7 4
Cases reported in 2015 3 3 0.083 0.190 (0.032-1.118) 0.244
Years Cases reported in 2016 3 1 0.594 0.714 (0.067-7.610) 0.733
Cases reported in 2017 19 6 0.343 0.609 (0.162-2.294) 0.744
Cases reported in 2018 20 1 0.029* 8 (0.943-64.864) 4.889
Table 2. Statistical association between pulmonary/non-pulmonary nocardiosis with gender, wards and no. of
cases in each year *significant p < 0.05; C.I: Confidence interval; RR: Relative risk.
number of cases in year 2018 were significantly
associated with Pulmonary nocardiosis with
greater risk (OR = 8; 95% CI = 0.943-64.864; RR
= 4.889; p0.029).
Antimicrobial susceptibilities
The sensitivity and resistance pattern of No-
cardia spp. is illustrated in Fig. 1. Fifty-six (56)
cases were resistant to ampicillin, cefepime,
piperacillin/tazobactam, doxycycline and clar-
ithromycin (56/56 = 100%) followed by
ciprofloxacin 60.75 (34/56), amoxicillin/clavu-
lanic acid 41.1% (23/56), ceftriaxone 41.1%
(23/56), tobramycin 39.3% (22/56), cefotaxime
32.1% (18/56) and imipenem 23.2% (13/56). In
the present study, all the collected Nocordia
spp. isolates were susceptible (100%) to
amikacin, linezolid, tetracycline and van-
comycin. Other effective choices were imipen-
em (76.8%), levofloxacin (87.5%) and trimetho-
prim / sulfamethoxazole (85.7%).
DISCUSSION
The diagnosis of nocardiosis is a big chal-
lenge. Usually the sign and symptoms for nocar-
diosis patients are not very specific. It develops
a doubtful opinion regarding the pulmonary in-
fections with different etiologies 17. The review
of literatures show that in last three decades, the
incidence of nocardiosis in Pakistan is low i.e.
6-10 cases per year 8but more frequently as
pulmonary nocardiosis 13,14. The reasons for this
low rate of isolation might be due to difficulties
in clinical diagnosis and their identifications.
The major risk factor in the study of population
was their initial diagnosis and treatment that
were usually dealt as bacterial infection and fun-
gal disease. The average incidence progressively
increased during January 2015 to June 2018, out
2423
of 56 cases of nocardios, 80.4% were pulmonary
nocardiosis. The results are supported by the
study reported by Farooqui et al. 15.
Overall the gender was not found statistically
significant and non-significant association was
reported between pulmonary nocardiosis and
male gender 2. Similarly, another study was re-
ported from Karachi, Pakistan that also revealed
the non-significant association 13. However, the
present investigation shows that the males are
more susceptible for pulmonary nocardiosis as
compared to females. Results are supported by
previously published studies 2,15,18,19. However,
the treatment choices were remained effective.
Total n = 21 cases were reported in year
2018 up to the month of June and 20 of them
were pulmonary nocardiosis with a significant
association (p < 0.05). The relative risk of pul-
monary nocardiosis is five times more in 2018 in
comparison with previous years. This finding is
to some extent related with the current environ-
mental condition of the Karachi because the city
undergoes massive diggings for various civil
construction projects in major populated areas
which pollute and increase the risk of pul-
monary nocardiosis.
In clinical practices, currently trimethoprim/
sulfamethoxazole (co-trimoxazole; SXT) is used
as first-line treatment option against nocardiosis
20. The present analysis shows the susceptibility
profile of Nocardia spp., to trimethoprim/sul-
famethoxazole (SXT) was 85.7%, supporting the
drug as first line of agent of treatment. Howev-
er, it seems that the resistance rate increased in
comparison with previously published reports
reveled 90.4% 15, 98% 21 and 100% 22. The in-
creased resistance of Nocardia spp., against SXT
was also reported in various studies 14,23,24.
Figure 1. Antimicrobial susceptibilities in Nocardia isolates (n =56); ampicillin (AMP), amoxicilin/clavulanic acid
(AMC), ceftriaxone (CRO), cefotaxime (CTX), cefepime (CFM), pipracillin/tazobactam (PTZ), amikacin (AMK),
tobramycin (TOB), trimethoprim/sulfamethoxazole (SXT), doxycycline (DOX), tetracycline (TCN), clar-
ithromycin (CLN), vancomycin (V), ciprofloxacin (CIP), levofloxacin (LEV), imipenem (IMP) and linezolid
(LZD).
In present investigation, Nocardia spp., were
100% susceptible to amikacin, linezolid, tetracy-
cline and vancomycin. The previous studies re-
ports also supported the finding that the linezol-
id and amikacin are the effective choices for the
treatment of nocardiosis 15,22,25,26.
The frequency of pulmonary nocardiosis is
increasing globally and it is more dominant in
tropical and subtropical environments. There-
fore, the environmental sampling studies are
suggested to identify the actual cause of the in-
cidence. In Iran, a study was performed to iso-
late the Nocardia spp., in hospital environment
24. On the other hand, the recurrent uses of dif-
ferent medicines such as corticosteroids or im-
munosuppressive agents due to newer diseases
like HIV, AID or cancers may also be the risks
of Nocardial infections.
CONCLUSION
Nocardiosis is a serious infection that has an
ability to make changes in its susceptibility
profile. The present study concluded that the in-
creasing incidence of pulmonary nocardiosis is
one of the alarming situations for the re-
searchers and clinicians. The occurrence of the
diseases is increasing in Karachi, Pakistan. It is
required to perform the study continuously and
follow standard protocols for isolation and iden-
tification of Nocardia spp for better patient
management in case of chest infections. It was
also concluded that trimethoprim/sulfamethoxa-
zole, amikacin, linezolid, vancomycin and tetra-
cycline are the effective choices of treatment.
Additionally, environmental risks must be mini-
mized in the city and hospital setup should be
modified to control dissemination of the nocar-
diosis.
Latin American Journal of Pharmacy - 40 (10): 2420-4 (2021)
2424
FATIMA S., JAMIL S., ISHAQ S., USMAN S., ANSER H. & OWAIS W.
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Infect. Dev. Ctries. 5: 499-501.
15. Farooqui, F., S. Irfan, S. Shakoor & A. Zafar
(2018) J. Global Antimicrob. Resist. 15: 219-21
16. Clinical and Laboratory Standards Institute
(2011) Susceptibility testing of mycobacteria,
nocardiae, and other aerobic actinomycetes;
approved standard. second edition Wayne, PA:
CLSI; CLSI document M24-A2.
17. Baio, P.V.P., J.N. Ramos, L.S. dos Santos, M.F.
Soriano, E.M. Ladeira, M.C. Souza, et al.
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20. Schlaberg, R., M.A. Fisher & K.E. Hanson
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