Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review
Abstract
:1. Introduction
2. Altered Immune Response in Diabetes
2.1. Oxidative Stress in Diabetes
2.2. Cytokine Response in Diabetes
2.3. Neutrophil Function and Other Immune Abnormalities in Diabetes
2.4. Immune Abnormalities in T1 Diabetes
3. Invasive Infection Susceptibility and Management in Diabetes
3.1. Invasive Aspergillosis Infection
3.2. Invasive Zygomycosis
3.3. Invasive Pneumococcal Infection
3.4. Invasive Rhinosinusitis
- (a)
- CRS without nasal polyps (CRSsNP)
- (b)
- CRS with nasal polyps (CRSwNP)
- (i)
- Aspirin-exacerbated respiratory disease (AERD)
- (ii)
- Allergic fungal rhinosinusitis (AFRS)
- (a)
- Type 1 (IFN-g)
- (b)
- Type 2 (IL-5, and IL-13)
- (c)
- Type 3 (IL-17)
3.5. Invasive Mucormycosis
3.6. Herpes Zoster Infection
4. Treatment Possibilities for Invasive Infection in Diabetes with Impaired Immunity
4.1. Treatment Possibilities for Invasive Aspergillosis Infection
4.2. Treatment Possibilities for Invasive Zygomycosis
4.3. Treatment Possibilities for Invasive Pneumococcal Infection
4.4. Treatment Possibilities for Invasive Rhinosinusitis
4.5. Treatment Possibilities for Invasive Mucormycosis
4.6. Treatment Possibilities for Herpes Zoster
4.7. The Role of Beneficial Bacteria in Diabetic Immuno-Comptonization
5. Conclusions and Future Direction
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Condition | Causative Organism | Patient/Number of Patients | Symptoms | Country | Diagnosis | Treatment | References |
---|---|---|---|---|---|---|---|
Renal Aspergillosis | Aspergillus fumigatus | Forty-five-year-old diabetic male | Mild pain in the left lumbar region; irregular, low-grade fever; and occasional dysuria for 3 months. | Malaysia | Ultrasound scan and intravenous urogram (IVU) revealed a cystic lesion (4 × 3.9 cm) at the lower pole cortical region of the left kidney. | Amphotericin B for 2 weeks at 1.25 mg/kg/day, which was replaced by oral itraconazole (200 mg twice daily for two months and 100 mg twice daily for one month) as the person could not tolerate Amphotericin B. | [58] |
Pulmonary aspergillosis | Aspergillus | (a) Forty-six-year-old diabetic female with hypertension (b) Forty-five-year-old diabetic male smoker | wheezing, chronic productive cough, and dyspnoea. Intermittent fever for a month, dyspnoea, dry cough, and weight loss. | Iran | Elevated ESR [erythrocyte sedimentation rate] (126 mm/1st h) and fasting blood sugar: 229 mg/dl; the galactomannan level in serum was 1.7. Chest X-ray showed cavitary formation in the right upper lobe, spiral CT-scan of thorax with revealed large cavitation in anterior segment of right upper lobe, trans-bronchial lung biopsy. Galactomannan serum level was 1.8. Elevated ESR (66 mm/1st h), white blood cells:18,700/mm3, Neut.: 88%, and blood sugar: 380 mg/dl. Cavitation in upper lobe nodules was revealed on chest X-ray and CT-scan of thorax. | Itraconazole Itraconazole | [159] |
Pulmonary aspergillosis | Aspergillus versicolor and Aspergillus ochraceus | Twenty-nine-year-old Type 1 diabetic male with marijuana use. | Chest pain for a week, weight loss, dyspnoea, fever, and night sweats for a year, | Canada | A radiograph of the chest showed pneumothorax and air space disease in the left lower lobe. Computed tomography of the chest showed consolidation and cavitation in the left lower lobe, annexing the pleura, pneumothorax, a chest tube and subcutaneous emphysema. | Surgery and six-months course of voriconazole. | [60] |
Pulmonary aspergillosis and mucormycosis | Aspergillus fumigatus, Rhizopus arrhizus | Seventy-nine-year-old diabetic, Latino male with hypertension and COVID-19 | Fever, rigors, dry cough, and dyspnoea for 10 days. | USA | Nasopharyngeal swab PCR (Polymerase Chain Reaction) test was positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Chest radiograph (CXR) revealed patchy bibasilar infiltrates. Computed tomography (CT) revealed moderate, bilateral, ground-glass opacities and infiltrates. On day 13, a broncho-alveolar lavage showed thick respiratory secretions. On day 19, the chest CT was repeated. | Five days of treatment with ceftriaxone, azithromycin, and remdesivir. A 7 day course of IV (intravenous) vancomycin 1250 mg every 8 h and IV ceftriaxone 1 g daily for treating ventilator-associated pneumonia. On day 14, 200 mg of IV voriconazole was administered twice daily for treating aspergillosis. From the 19th, day liposomal Amphotericin B was started for treating mucormycosis. On day 23, a tracheostomy was performed, and on day 25 was a percutaneous endoscopic gastrostomy. | [160] |
Pulmonary aspergillosis | Aspergillus fumigatus | Forty-four-year-old diabetic male | Fever, haemoptysis, cough, and dyspnoea for 3 weeks. | India | Sputum analysis for fungus, chest X-ray, and contrast-enhanced computed tomography were performed, which showed multifocal areas of cavitation involving bilateral upper and lower lobes of the lung. Patient underwent flexible bronchoscopy and subsequent biopsy. | IV voriconazole, 6 mg/kg b.d., followed by 4 mg/kg b.d. for 2 weeks. | [161] |
Pulmonary aspergillosis | Aspergillus fumigatus | Forty-five-year-old diabetic male with ketoacidosis and hypertension. | Flu-like illness with pyrexia. | UK | Chest radiography showed patchy consolidation and volume loss of the left lower zone. Bronchoscopy showed thick, white plaques over the left main bronchus, extending into left upper and lower lobe bronchi. | Initially started with intravenous cefotaxime, flucloxacillin, and metronidazole. From day, 5 piperacillin, gentamicin and metronidazole were administered. Intravenous fluconazole was given for candida albicans infection. From day 7, oral itraconazole, 200 ug b.d., and an intravenous amphotericin B colloidal dispersion (2 mg/kg bw increased to 4 mg/kg bw) were treated. Itraconazole was given for six months. | [162] |
Pulmonary aspergillosis | Aspergillus | Fifty-three-year-old diabetic female with keto-acidosis. | Fever, vomiting, and confusion. | Japan | A chest radiograph demonstrated infiltrates in the middle and lower zones of both lungs. A chest CT scan showed nodules with the halo sign and focal ground glass opacity and cavitation. Bronchoscopy showed thick, white plaques. | Intravenous ampicillin sodium/sulbactam and peramivir were initiated for her pneumonia. This was shifted to L-amphotericin B (100 mg/body per day for a month). | [163] |
Pulmonary aspergillosis/aspergilloma | Aspergillus sp. | Forty-five-year-old diabetic female | Chest pain, cough, decreased appetite, weight loss, and chronic haemoptysis. | Indonesia | X-ray and CT scan showed a mass in the upper lobe of left lung. Fine needle aspiration biopsy showed Aspergillus sp. surgery. | Initial treatment included the administration of codeine (3 × 10 mg), tranexamic acid (3 × 500 mg iv), novorapid (3 × 10 units), evemir (12 units, night), and Fluconazole (1 × 400 mg for 1 day, followed by 200 mg). Surgery was performed using pulmonary wedge resection | [164] |
Rhino-oculo-cerebral aspergillus and mucor co-infection | Rhizopus & Aspergillus flavus | Forty-six-year-old diabetic male with hypertension and epistaxis in his past | proptosis of the left eye, ptosis, and diminution of vision for a month. Confused state | India | The radiological examination revealed opacification. Squamous cell carcinoma revealed on histopathology. X-ray and CT scan were performed for diagnosis. Sinoscopy confirmed a severely inflamed maxillary sinus. Fifteen days after the diagnosis of aspergillosis, histopathological studies revealed septate hyphae showing mucor infection. | Voriconazole treatment for seven days. After 15 days, Amphotericin B was given, but the patient expired due to intolerance. | [165] |
Condition | Causative Organism | Patient/Number of Patients | Symptoms | Country | Diagnosis | Treatment | References |
---|---|---|---|---|---|---|---|
Gastrointestinal | Zygomycosis | Thirty-six-year-old diabetic female | Epigastric-pain, bilious vomiting, weight loss, fever, and constipation. | Iran | Endoscopy disclosed an extensive sub-mucosal haemorrhage. A biopsy demonstrated broad, aseptate fungal elements, a laparotomy showed rubbery, grey/brown necrotic tissue | Total gastrectomy with Roux-en-Y esophago-jejunostomy and surgical debridement, Amphotericin B lipid complex (1 mg/kg/dose). | [167] |
Cutaneous | Rhizopus arrhizus | Twenty-six-year-old diabetic female with ketoacidosis. | Severe lower abdominal pain and intense thirst. | India | Biopsy specimen showed non-septate hyphae with right angle branching. | Local surgical debridement and Amphotericin B (4 mg/kg/day). | [168] |
Cutaneous and rhino-orbitocerebral | Apophysomyces elegans | Fifty-year-old diabetic male | Facial pain and diplopia, right eye proptosis. | USA | Physical examination, CT, and MRI of the head showed right eye proptosis with inflammatory changes. Histopathology showed aseptate hyphae. | Liposomal Amphotericin B and multiple debridements. | [169] |
Urinary bladder | Mucorales | Fifty-five-year-old diabetic male | Fever, dysuria, obstructive urinary symptoms, deranged creatinine, and flank pain. | India | Non-contrast CT scan showed right mild hydronephrosis. Cystoscopy showed yellowish-white material in urinary bladder. Histopathology studies revealed the fungal attack. | Posaconazole | [170] |
Pulmonary | Rhizopus oryzae | Sixty-one-year-old diabetic male | Productive cough, fever, anorexia, and weakness. | India | A thick-walled cavity in the hilar region was seen from the chest X-ray. CECT (contrast-enhanced computed tomography) of the chest revealed a cavitating lesion. Histopathological studies showed fungal hyphae. | Amphotericin B for a cumulative dose of 3 g. | [171] |
Age at First Dose (Months) | Primary Dose | Booster Dose | Reference | |
---|---|---|---|---|
Pn7 | Pn7 | PPV23 | ||
2–6 months | 3 doses (2/4/6 months) | 12–15 months of age | After 2 years of age. | [176,177,178,179] |
7–11 months | 2 doses (0/2 months) | 12–15 months of age | First dose: At least 6–8 weeks after the last dose of pnc7. | |
12–23 months | 2 doses (0/2 months) | None | Second dose: 5 years after the pn23 dose. | |
≥24 months | 2 doses (0/2 months) | None | - | [89,176,177,178,179] |
5–64 years | None | None | None | [89,180] |
>64 years | None | None | Second dose if the vaccine was administered >5 years ago. |
Underlying Diseases | Organ/Region Infected with Fungus | Objective | Patient/Number of Patients | Country | Methodology | Results and Conclusion | Reference | |
---|---|---|---|---|---|---|---|---|
Diabetes | Lungs | Pulmonary mucormycosis and tuberculosis | A diabetic case with fungal co-infection. | A fifty-six-year-old female | Netherlands | X-ray, CT scan, RTPCR, and lobectomy. | Treatment with TB and mycosis medicines resulted in little side effects. Patients with diabetes should undergo testing for certain co-infections | [195] |
Diabetes mellitus | Eye | Mucormycosis | Infarction of the optic nerve caused by mucormycosis in a diabetic patient. | A fifty-one-year-old male | USA | MRI, exenteration and sinus debridement. | Extensive infarction of the left optic nerve with inflammation of the ipsilateral and periorbital adnexa. Histopathology demonstrated the presence of mucormycosis. | [196] |
Renal failure and diabetes mellitus | Eye | Mucormycosis | ROCM detected in an ocular nerve infection case. | A thirty-four-year-old man. | Taiwan | Ophthalmic and neurological examination, CSF (cerebrospinal fluid) examination, and MRI. | There were black eschars going from the bilateral canthi to the vascular area. It extended to cerebral and bilateral ophthalmic nerves. People with immunocompromised patients might consider ROCM if they have neuro-ophthalmological symptoms. | [197] |
Diabetic ketoacidosis with ophthalmoplegia | Nostril region | Mucormycosis | An instance of recovery from mucormycosis infection. | A twenty-two-year-old women | USA | CT scan, nasoendoscopy, and biopsy. | Surgical excision of the right eye, paranasal sinuses, maxilla, and palate, suboccipital craniectomy, and shunt for hydrocephalus, followed by an 18 month course of antifungal medication. The chance of infection was increased with several surgical procedures. | [198] |
Diabetes, kidney failure, myelodysplastic syndrome, and acute leukaemia | Cerebral region | Mucormycosis | Retrospective study of 36 cases with Mucormycosis | Thirty-six cases | Mexico | Surgical debridement, CT scan, and MRI. | Systemic and rhino-cerebral mucormycosis. The report suggested medicinal and surgical treatment. | [199] |
HIV infection and diabetes | Cerebral region | Mucormycosis | Mucomycorsis with vasculitis in a diabetic case. | A fifty-four-year-old woman | Brazil | CSF analysis, CT scan, histopathologic analysis, and angiography with HR-VWI (high-resolution vessel wall imaging). | Vasculitis accompanied with inflammation. More research is necessary to evaluate the accuracy of mucormycosis tests. | [200] |
Diabetes mellitus | Cerebral region | Mucormycorsis | Progressive ophthalmoplegia and blindness in infection. | Eighteen-year-old woman | USA | Surgical debridements, MRI, lumbar puncture, funduscopic examination, and surgical debridement. | Observation of fungal hyphae in the ophthalmic artery and optic nerve perineurals in the absence of substantial optic nerve inflammation. Diabetic individuals with ophthalmoplegia and blindness should be evaluated for infection. | [201] |
Diabetes mellitus (three patients) and chronic leukaemia (one patient) | Cerebral region | mucormycosis | Examining fungal infections in four patients with underlying illnesses. | Four cases | Turkey | CT scan Otorhinolaryngologic examination | There were neurological abnormalities detected. Two patients had passed away. Investigating mucormycosis in ophthalmoplegia and ensuring quick diagnosis should be considered. | [202] |
Diabetes mellitus with Cushing’s syndrome | Cerebral region | Mucormycosis | Cushing’s syndrome and solid tumours are associated with infection. | Forty-two-year-old woman | Mexico | CT scan Autopsy | Infarction of the left temporal lobe. The cause of the patient’s death was determined to be a multihormonal pituitary adenoma with expansion to the sphenoid bone and sellar erosion. ACTH (ectopic adrenocorticotropic hormone) was detected in the left lung. The research established a correlation between ACTH and ectopic pulmonary tumours, pituitary apoplexy, and mucormycosis. | [203] |
Diabetes mellitus and immunosuppression conditions | Cerebral region | Mucormycosis | Reginal differences in the infection and its causes. | - | Middle East and North Africa | Data collection | A total of 310 instances of infection. Most cases were associated with diabetes and immunosuppression. It is necessary to put into practice efficient treatment and preventive measures. | [204] |
Diabetes | Cerebral region | Mucormycosis | A case of diabetes infected with mucormycosis. | Elder man | Canada | CT scan Autopsy | Thrombosis with infection in cerebral region. Early diagnosis is the key to effective therapy. | [205] |
Diabetes mellitus with Garcin syndrome | Cerebral region | Mucormycosis | Analysis of infection and tuberculosis meningitis in a case with underlying disease. | - | China | CT scan with X-ray | Tuberculosis meningitis developed to mucormycosis. Diagnostics should be first in identifying the infection. | [206] |
Diabetes mellitus | Cerebral region | Mucormycosis | To determine the prevalence and risk factors of mucormycosis in individuals with diabetes mellitus. | Total of 162 patients | Iran | Detailed history, otorhinolaryngologic, ophthalmic, and neurologic examinations | A total of 30 individuals had diabetes (19 were women and 11 were men). Diabetes might be a risk factor for fungal infections. | [207] |
Diabetes mellitus | Cerebral region | Mucormycosis | Identification of infection in diabetes patient with complication to acute infarction | Fifty-seven-year-old man | Iran | CT scan Biopsy | Subarachnoid haemorrhage associated with a stroke. The biopsy revealed a mucormycosis infection. Early actions are required to prevent severe consequences. | [208] |
Diabetes mellitus | Sinus region | Rhizopusaarhisus | To estimate the distribution of infection and its associated factors. | A total of 208 cases | Iran | Sequencing and data collection. | From 2008 to 2014, there was an increase in infections. It is crucial to monitor and identify this infection. | [209] |
Diabetes and non-diabetic patients | Rhino-orbito- cerebral | Mucorales | To compare fungal infections in people with and without diabetes. | Total of 63 patients | Iran | Ophthalmic investigation, imaging studies, and biopsy. | Survival was recorded in 51% of diabetic patients and 70% of non-diabetic patients. Neither group’s rate of vision survival differed from the other. | [210] |
Diabetes mellitus, Malignancy, transplant | Rhino-orbital | Rhizopus | Mucormycosis was the subject of a prospective observational research that was carried out across 12 locations in India. | Total of 465 patients | India | Questionnaire analysis | Symptoms with a shorter duration. The shorter duration of antifungal medication and the use of Amphotericin B were independent risk factors for death. Diabetes was the primary risk factor. | [211] |
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Khanam, A.; Hithamani, G.; Naveen, J.; Pradeep, S.R.; Barman, S.; Srinivasan, K. Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review. Biologics 2023, 3, 40-71. https://doi.org/10.3390/biologics3010004
Khanam A, Hithamani G, Naveen J, Pradeep SR, Barman S, Srinivasan K. Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review. Biologics. 2023; 3(1):40-71. https://doi.org/10.3390/biologics3010004
Chicago/Turabian StyleKhanam, Anjum, Gavirangappa Hithamani, Jayapala Naveen, Seetur R. Pradeep, Susmita Barman, and Krishnapura Srinivasan. 2023. "Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review" Biologics 3, no. 1: 40-71. https://doi.org/10.3390/biologics3010004