Respiratory tract infections in

diabetes

C. LlorPrimary Healthcare Centre Via Roma,

Barcelona

Research Support

- 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 (Spanish Ministry of Health)-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, speakers bureau, honoraria

None

Competing interests

Common in diabetics

Pyelonephritis, cystitis, perinephric abscess

Periodontitis

Soft tissue infections including diabetic foot & osteomyelitis

Onychomycosis

Necrotizing fasciitis

Mucocutaneous candidiasis

Tuberculosis

Exclusively in diabetics

Invasive (malignant) otitis externa

Rhinocerebral mucormycosis

Emphysematous infections (pyelonephritis & cholecystitis)

Infections in diabetes

Pathophysiology of infections associated with diabetes mellitus

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

Infectious diseases in primary care

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

• 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

Pulmonary infections

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.

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

Prognostic factor n Death Mort. (%)

Adjusted. MRR (95% CI)

p

30 days

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

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)

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

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.

Glucose level (mmol/l) n DeathMort.

(%)Adjusted MRR

(95% CI)* PType 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

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

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, ethnicity, smoking, BMI, education, alcohol consumption, and number of outpatient visits

Hazard ratio (95% CI) for the association between each pulmonary condition and

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.

• 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

Tuberculosis and diabetes

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.

Exposure status

Number of TB cases/ 100,000 personyears at

risk

Age-adjusted rate (95%

CI)

Age-adjusted rate ratio (95% CI)

Fully adjusted

model. Rate ratio (95%

CI)

Patients without diabetes 779/57.68

13.51 (12.59–14.49)

1.00 1.00

Patients with diabetes 190/11.73

16.20(14.05–18.68)

1.20(1.02–1.40)

1.30(1.01–1.67)

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

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

• 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

Antimicrobial resistance: The post-antibiotic era

• 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

Drawbacks in the management of respiratory tract infections in primary care

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

Consumption Resistance

ConsumptionResistance

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

Negative correlation between consumption & resistance and utilisation of rapid tests

No tests

CRP, Strep A, WBC, FlexiCult

*Countries reporting only outpatient antibiotic useRomania and Spain provided reimbursement data

Total antibiotic use in 2011, expressed in number of DDD per 1,000 inhabitants per day in Europe

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 duration of symptoms

When are antibiotics indicated in diabetic patients?

Acute otitis media

4 days <2 yr. always; > 2 yr if risk factors (fever,otorrhoea, severity, bilaterality, ear drum perfor.)

Acute sore throat

1 week If caused by S. pyogenes, also 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 rhinosinusitis

2½ weeks If symptoms and signs do not improve after 10 days, severe patient after the 3rd day or worsening

of symptoms after the fifth day

Acutebronchitis

3 weeks Rule out pneumonia. Consider antibiotics in severe patients

Lack of time

Communication: Probably not his...?

Or this...?

More research is needed

Getting further funds?

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

Take-home messages

E-mail: carles.llor@gmail.com