Respiratory tract

infections in
diabetes
C. Llor
Primary Healthcare Centre Via Roma,
Barcelona
Competing interests

- I am receiving research grants from the European

Commission (Sixth, Seventh Programme Frameworks and
Horizon 2020)
- I am receiving grants from the Instituto de Salud Carlos III
Research
(Spanish Ministry of Health)
Support
-I received grants from the Catalan Society of Family
Medicine
- Grant from the Fundació Jordi Gol i Gurina for a research
stage at the University of Cardiff in 2013
Employee,
consultant,
stakeholders, None
speakers bureau,
honoraria
Infections in diabetes

Common in diabetics Exclusively in diabetics

Pyelonephritis, cystitis, Invasive (malignant) otitis
perinephric abscess externa
Periodontitis Rhinocerebral mucormycosis
Soft tissue infections including Emphysematous infections
diabetic foot & osteomyelitis (pyelonephritis & cholecystitis)
Onychomycosis
Necrotizing fasciitis
Mucocutaneous candidiasis
Tuberculosis
Pathophysiology of infections associated with diabetes mellitus
Infectious diseases in primary care

Infectious diseases account for 33.2% of all the visits in primary care

Infectious disease %
1 Acute pharyngotonsillitis 14.1
2 Common cold 13.2
3 Acute bronchitis 9.4
4 Acute cystitis 9.3
5 Infectious diarrhoea 6.8
6 Infectious conjunctivitis  5.4
7 Infected wound or ulcer 4.2
8 Candidal vaginitis 3.6
9 Exacerbation of CB/COPD 3.5
10 Acute sinusitis 3.5
Pulmonary infections

• Increased frequency for infections caused by Staphylococcus aureus,

gram negative organisms, Mycobacterium tuberculosis
• Diabetics are 3 times more likely to colonize S. aureus in their
nasopharynx. They are also colonized with gram negative bugs at times
• Diabetics with pneumococcal pneumonia might be more likely to be
bacteremic or die from it (OR=1 - 1.3)
•  mortality and incidence of bacterial pneumonia during epidemics of
influenza
• It is recommended that diabetics receive the pneumococcal vaccine &
annual flu vaccine
• Treatment regimes remain same as for non-diabetics
Two main objectives:
- Whether type 2 DM increases risk of death and complications following
pneumonia
- Assess the prognostic value of admission hyperglycaemia

Kornum JE al. Diabetes Care 2007;30:2251–7.

Adjusted mortality within 30 and 90 days among patients
hospitalized for pneumonia

Prognostic factor n Death Mort. Adjusted. MRR p

(%) (95% CI)
30 days
No diabetes 26,877 4,098 15.1 1.0 (ref.)
Type 2 diabetes 2,931 882 19.9 1.16 (1.07 – 1.27) <0.01

90 days
No diabetes 26,877 5,818 21.6 1.0 (ref.) 0.02
Type 2 diabetes 2,931 791 27.0 1.10 (1.02 – 1.18)

Kornum JE al. Diabetes Care 2007;30:2251–7.

Mortality curves for patients hospitalized with pneumonia,
according to presence of diabetes & level of Charlson index score

Kornum JE al. Diabetes Care 2007;30:2251–7.

Adjusted mortality within 30 days among pneumonia patients
with available glucose values on admission

Mort. Adjusted MRR

Glucose level (mmol/l) n Death (%) (95% CI)* P
Type 2 diabetes patients 1,307
≤6.1 279 52 18.6 1.0 (ref.)
6.11–11.0 545 95 17.4 0.96 (0.69–1.35) 0.82
11.01–13.99 188 40 21.3 1.24 (0.82–1.88) 0.31
≥14 295 65 22.0 1.46 (1.01–2.12) 0.04

Non diabetic patients 9,107

≤6.1 4,850 675 13.9 1.0 (ref.)
6.11–11.0 3,901 808 20.7 1.43 (1.29–1.59) <0.01
11.01–13.99 195 46 23.6 1.65 (1.23–2.23) <0.01
≥14 161 42 26.1 1.91 (1.40–2.61) <0.01
Kornum JE al. Diabetes Care 2007;30:2251–7.
Outcomes among patients aged 65 or older with pneumonia

Kofteridis DP et al. JAGS 2016;64:649–51.

Analysis of the relationship between diabetes and the occurrence
of lung diseases

Adjusted for age, gender, Hazard ratio (95% CI) for the
ethnicity, smoking, BMI, association between each
education, alcohol consumption, pulmonary condition and
and number of outpatient visits diabetes status

Asthma 1.08 (1.03 – 1.12)

Chronic obstructive pulmonary disease 1.22 (1.15 – 1.28)
Pulmonary fibrosis 1.54 (1.31 – 1.81)
Pneumonia 1.92 (1.84 – 1.99)
Lung cancer 1.10 (0.96–1.26)

Ehrlich SF al. Diabetes Care 2010;33:55–60.

Tuberculosis and diabetes

• Relative risk of developing active disease 1-2 times that of general population.
TB patients screened for DM?1,2
• Highly increased risk of multi-drug resistant tuberculosis
• Most guidelines recommends that preventive chemotherapy be given to
diabetics who have a TST > 10 mm and no active disease
• DM patients had increased frequency of lung lesions confined to lower lung
and more cavitary lung lesions compared with patients with TB but no DM3
• An increase in dose of sulfonylureas may be needed if rifampicin is co-
administered
• Treatment is the same. Bacteriological conversion and relapse rates are same
as non-diabetics

1Ogbera AO et al. BMJ Open Diab Res 2015;3:e000112; 2Viswanathan V et

al. PLoS One 2012;7:e41367.; 3Shaikh MA et al. Suadi Med J 2003;24:1073–
6.
Patients followed from 1990 to 2012:
-222,731 diabetics
- 1,218,616 matched controls
- The authors assumed that UK incidence rates of tuberculosis did not vary
over time
Pealing L et al. BMC Med 2015;13:135.
Tuberculosis and diabetes. Causal diagram of associations
between diabetes, tuberculosis and confounders

Pealing L et al. BMC Med 2015;13:135.

Tuberculosis and diabetes. Rates and adjusted rate ratios for all
types of tuberculosis by exposure to diabetes

Exposure Number of Age- Age- Fully

status TB cases/ adjusted adjusted adjusted
100,000 rate (95% rate ratio model. Rate
person CI) (95% CI) ratio (95%
years at CI)
risk
Patients without 13.51
779/57.68 1.00 1.00
diabetes (12.59–14.49)
Patients with 16.20 1.20 1.30
190/11.73
diabetes (14.05–18.68) (1.02–1.40) (1.01–1.67)

Pealing L et al. BMC Med 2015;13:135.

Antimicrobial resistance: The post-antibiotic era

• Simple infections become untreatable or even

fatal

• Many medical procedures become impossible

without effective antibiotic protection, e.g.
- No heart surgery or transplantations
- No immune-modulating therapy for rheumatoid
arthritis or cancers of the blood
- Limited routine operations such as hip
replacements
- Reduced survival of pre-term babies

• Shortages of food due to untreatable infections in

livestock

• Restrictions on trade in foodstuffs

• Restrictions on travel and migration

Drawbacks in the management of respiratory tract infections in
primary care

• The diagnosis of most respiratory tract infections is generally unclear and

casts many doubts
• A single best treatment is not available in most respiratory tract infections
• GPs do not know the best treatments available and fail consistently to apply
them
• GPs do not usually uniformly communicate the progression of the
respiratory tract infections
• GPs are in the best position to evaluate trade-offs between different
treatments and to make treatment decisions
• Self-consumption of antibiotics and sale of antibiotics without prescription
in community pharmacies

Butler CC et al. J Antimicrob Chemother 2001;48:435–40.

Drawbacks in the management of respiratory tract infectious diseases in primary 
care

Negative correlation between consumption & resistance and utilisation of rapid tests

Consumption 
Resistance

CRP, Strep A, 
WBC, FlexiCult

Consumption
Resistance

No tests
Total antibiotic use in 2011, expressed in number of DDD per
1,000 inhabitants per day in Europe

*Countries reporting only outpatient antibiotic use

Romania and Spain provided reimbursement data Versporten A et al. Lancet Infect Dis 2014;349:g5238.
‘A 44% of UK GPs admit to have prescribed antibiotics to get a patient
to leave the surgery’

Cole A. BMJ 2014;349:g5238.

Management of the other respiratory tract infections in primary care

Condition Average When are antibiotics indicated in diabetic

duration of patients?
symptoms
Acute otitis 4 days <2 yr. always; > 2 yr if risk factors (fever,
media otorrhoea, severity, bilaterality, ear drum perfor.)
Acute sore 1 week If caused by S. pyogenes, also
throat immunocompromised, history of rheumatic fever,
streptococcal community outbreak, severity
Influenza 1 week Refer if suspected pneumonia, severity or pulse
oxymetry<92%
Common cold 1½ weeks
Acute 2½ weeks If symptoms and signs do not improve after 10
rhinosinusitis days, severe patient after the 3rd day or worsening
of symptoms after the fifth day
Acute 3 weeks Rule out pneumonia. Consider antibiotics in severe
bronchitis patients
Communication: Probably not his...?

Lack of time
Or this...?
More research is needed

Getting further funds?

Take-home messages

1 Infections caused by certain organisms, such as Staphylococcus aureus,

gramnegatives, and Mycobacterium tuberculosis, occur with increased
frequency in diabetic patients.
2 Infections due to common germs are associated with slightly increased
morbidity, severity and mortality.
3 Risk of pneumonia is 1.1 – 1.9 times increased in diabetic patients, with
increased risk of hospitalisation, and more mortality.
4 Diabetics more likely need hospitalisation during influenza epidemics.
Prevention is crucial.
5 Patients with diabetes are at higher risk of contracting tuberculosis.
Increased risk of multidrug resistant tuberculosis.
6 Same recommendations for other respiratory tract infections for both
diabetic and non-diabetic individuals. However, more research is needed
E-mail: carles.llor@gmail.com