More bacterial infections and diabetes

It is estimated that there were over 13.7 million (10.9–17.1) infection-related deaths worldwide in 2019. Sadly, among them will be many people with diabetes – more vulnerable to infection, and more likely to have complicated or hidden infections.1 In Brazil, a 21-year-old man with Prader-Willi syndrome was admitted with diabetic ketoacidosis and fever after two weeks of multiple antibiotics for left ear pain and discharge. CT showed left mastoid erosion, and discharge with gas in the ear canal, and involvement of adjacent face, neck, external ear, and parotid gland. No organism was grown. After a stormy course, with more antibiotics including vancomycin and meropenem, he recovered.2 Malignant or necrotising otitis externa (MOE, diabetic ear) is an invasive infection of the external ear canal spreading to the temporal bone and beyond. It is more common in older people, men, and in high humidity. Otitis externa (with ear canal inflammation, pain, swelling, and sometimes hearing loss) ultimately affects 1 in 10 people. In Taiwan the annual incidence of MOE was 0.221 per 100,000 people; 52.9% of patients had diabetes.3 In another study of 753 people with MOE and 2259 matched controls, 24.2% of all 3012 had diabetes. After adjusting for demographics and comorbidities, the odds ratio for having diabetes among people with MOE versus controls was 10.07 (8.15–12.44).4 Obligatory major criteria for diagnosing MOE are ‘Pain…oedema, exudate, granulations…in the external auditory canal, microabscess (when operated), positive bone scan technetium-99 (99Tc), failure of local treatment of more than 1 week.’ Pseudomonas aeruginosa is the commonest organism, then fungi, staphylococci, Proteus spp, and Klebsiella. Mortality has fallen from 50% to 10–20%.5 A 59-year-old woman with type 2 diabetes was admitted with worsening right-sided abdominal pain, vomiting, abdominal distension, and absolute constipation. She had reduced lower right breath sounds, abdominal distension with right-sided tenderness, and absent bowel sounds. ‘A plain AXR was reported as showing gas in the transverse colon and rectum.’ Urine contained blood and nitrites. Because of past appendectomy and hysterectomy, urinary tract infection and adhesional bowel obstruction were diagnosed. Her urine grew Escherichia coli. Despite treatment she deteriorated. CT showed right hydronephrosis, a dilated gas-filled pelvicalyceal system and a stone blocking the pelvi-ureteric junction. She eventually had a nephrectomy and recovered. ‘In retrospect, the admission AXR showed a large calculus at the level of the L3 vertebra on the right, and gas in the right renal pelvis.’6 Emphysematous pyelonephritis (EPN) may cause pneumaturia. Usual organisms are E. coli (70%), then Klebsiella pneumoniae (29%), and Proteus.6 Urinary tract infections are common; EPN is not. A meta-analysis included 1303 people with EPN with a mortality rate of 13%. The prevalence of diabetes was 79%. Patients with sepsis were more likely to die but having diabetes did not appear to worsen prognosis.7 ‘A 49-year-old woman with type 2 diabetes mellitus and nonadherence to insulin therapy presented with…urinary frequency, urinary incontinence, and pneumaturia.’ On plain X-ray, her bladder was distended with gas which was also seen in the bladder wall as a dark ‘beaded necklace’ within the pelvis, characteristic of emphysematous cystitis (ECY). She had multi-resistant E. coli. Catheter drainage and antibiotics were successful.8 As with EPN, most patients with ECY have diabetes (67% in a review). It is more common in women than men; other risk factors are neurogenic bladder, recurrent urinary tract infection, and bladder outlet obstruction. Mortality is 3–12%, rising by 14–20% with additional EPN. Usual organisms are E. coli (48%), Klebsiella pneumoniae (12%), Enterobacter, Proteus, and Streptococcus. Symptoms of ECY are those of cystitis and, sometimes, pneumaturia (gas in urine or bubbling interrupting urine stream). Do a CT to seek spreading infection or other causes of pneumaturia such as fistula.9 A 77-year-old Japanese man was admitted with falls, epigastric pain and lassitude. His abdomen was distended with upper tenderness. ‘Plain abdominal radiography showed the presence of intestinal gas.’ CT scan showed massive intra-abdominal gas with ascites, gas in the gall bladder, and a pleural effusion. At operation the abdomen was full of pus and a perforation was found in the gall bladder which was removed. Clostridium perfringens was grown. The patient recovered on antibiotics.10 Emphysematous cholecystitis (ECC) occurs in 1–3% of episodes of cholecystitis. It is defined by the presence of gas in the walls and lumen of the gallbladder. Organisms include clostridia, Klebsiella, E. coli, enterococci, and anaerobic streptococci.11 Fifty percent of people with ECC have diabetes. Cholecystitis is rarely fatal (mortality about 1–4%), but mortality in ECC is 15–20%.12 ‘Early recognition of emphysematous cholecystitis is necessary to avoid the high mortality that this fulminant condition carries. In a patient with diabetes mellitus and renal failure who presents with right upper quadrant abdominal pain and hypotension, emphysematous cholecystitis should be high on the diagnostic possibilities.’ So should EPN.11 A 14-year-old boy with type 2 diabetes and poor glycaemic control was admitted with five days of fever, cough, diarrhoea, vomiting, and abdominal pain. He had raised inflammatory markers and liver function tests. A CT scan showed a large liver abscess. He had hypervirulent Klebsiella pneumoniae bacteraemia. He died despite intensive treatment.13 Klebsiella pneumoniae liver abscesses usually occur in people without biliary tract disease. The hypervirulent strain often affects multiple sites, for example, the central nervous system or eyes. Hypervirulent Klebsiella pneumoniae is seen mainly in Asian Pacific Rim countries but is spreading.14 Diabetes affects 63% of patients in Taiwan with pyogenic liver abscess but in only about 7% of European patients.15 After age adjustment, ‘HbA1c level and abscess <5cm were independent risk factors for metastatic complications from Klebsiella pneumoniae liver abscess.’16 Klebsiella pneumoniae can be found in the gut of healthy people. A study typed Klebsiella variants in faeces and liver pus of people with liver abscesses; they matched, suggesting that patients’ own intestinal flora infected them.17 A 37-year-old Indian farmer with metformin-treated diabetes was admitted with fever, headache, vomiting, and abdominal pain. He was tachycardic and had right hypochondrial tenderness with 2cm hepatomegaly. Investigations showed diabetic ketoacidosis which was treated. CTs showed multiple small pulmonary nodules, a right psoas abscess, and hepatosplenomegaly. Blood and bone marrow cultures grew Burkholderia pseudomallei diagnosing melioidosis. He recovered after receiving imipenem, ceftazidime, sulfamethoxazole, trimethoprim, doxycycline, and insulin.18 Melioidosis is common in South East Asia and Northern Australia but can present anywhere.19 People catch melioidosis through direct contact with contaminated soil or water via skin breaks, inhalation, or ingestion. Melioidosis may be acute or subclinical, emerging weeks or even years after exposure. It has multiple presentations, the commonest being respiratory with chest infection, cough, chest pain, high fever, headache, and myalgia. Pulmonary cavities on chest X-ray may suggest tuberculosis. Localised infection includes a skin nodule, abscess or ulcer with fever and myalgia. Bloodstream infection is more likely in people with reduced immunity such as diabetes and leads to multiple abscesses, especially in liver, spleen or prostate. The patient becomes rapidly unwell and may develop septic shock.20 Diabetes is the main risk factor for melioidosis; others include alcoholism, liver or renal failure, chronic lung disease, HIV/AIDS. A systematic review found that 45.68% (44.8–46.57) of people with melioidosis had diabetes who were three times more likely to get melioidosis than those without diabetes (risk ratio 3.40, 2.92–3.87). Melioidosis has natural immunity to some antibiotics. ‘B. pseudomallei isolates were found sensitive to ceftazidime, cotrimoxazole, carbapenems (imipenem, meropenem), doxycycline and amoxicillin–clavulanate and resistant to ampicillin, aminoglycoside, ciprofloxacin, cefotaxime, and colistin.’21 Otitis externa is common. Malignant otitis externa is rare – consider it in severe, persistent otitis externa in people with diabetes. Infection can hide in many places in the abdomen of a person with diabetes who may or may not have abdominal symptoms. The intra-abdominal infections described are rare but are all more likely in people with diabetes than in those without. Remember emphysematous pyelonephritis, cystitis, and cholecystitis. Always investigate pneumaturia. Test for diabetes after diagnosing gas-forming infections in people without known diabetes. Plain abdominal films frequently show intestinal gas. Is all the gas in the gut? Check plain abdominal X-rays carefully in ill people with diabetes with abdominal or urinary symptoms. CT is better. In the Asian Pacific Rim many patients with Klebsiella pneumoniae liver abscess have diabetes and may have a hypervirulent organism. If people with diabetes with a puzzling infection, especially with respiratory or skin involvement, or an internal abscess, have been in South East Asia or Northern Australia, remember melioidosis. Helping everyone with diabetes to achieve good diabetes care, including access to trained and supported use of diabetes technology, with better knowledge, early detection and treatment of unusual infections, and advances in laboratory technology, could reduce the morbidity and mortality of these damaging diseases.