Chang Kyung Kang

Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea

Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.

agr Dysfunction Affects Staphylococcal Cassette Chromosome mec Type-Dependent Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia

ABSTRACT Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea.

Can a routine follow-up blood culture be justified in Klebsiella pneumoniae bacteremia? A retrospective case-control study.

BackgroundThe need for mandatory confirmation of negative conversion in Klebsiella pneumoniae bacteremia (KpB) has not been adequately addressed. We conducted a retrospective case–control study of adult patients with KpB over a 5-year period in two tertiary-care hospitals to determine the risk factors for persistent bacteremia and to reevaluate the necessity of follow-up blood culture in KpB.MethodsPersistent KpB is defined as the finding of K. pneumoniae in more than two separate blood-culture samples for longer than a two-day period in a single episode. The case- and control-groups were patients with persistent and non-persistent KpB, respectively, and they were matched 1-to-3 according to age and gender.ResultsAmong 1068 KpB episodes analyzed after excluding polymicrobial infection and repeated KpB, follow-up blood cultures were performed in 862 cases (80.7%), 62 of which (7.2%) were persistent. Independent risk factors for persistence were intra-abdominal infection, higher Charlson’s comorbidity weighted index score, prior solid organ transplantation, and unfavorable treatment response, which was defined as positivity for at least two parameters among fever, leukocytosis, and no decrease of C-reactive protein on the second day after initial culture. A proposed scoring system using four variables, namely, intra-abdominal infection, nosocomial KpB, fever and lack of C-reactive protein decrease, the last two being assessed on the second day after the initial blood culture, showed that only 4.9% of the patients with no risk factors or with only intra-abdominal infection had persistent KpB.ConclusionsThough persistent KpB is uncommon, follow-up blood culture was performed in as many as 80% of the cases in this study. A more careful clinical assessment is warranted to reduce the cost and patient inconvenience involved in follow-up blood culture.

Penicillin G-induced hemorrhagic cystitis: a case and review of the literature

To the Editor, Penicillin is the first b-lactam antibiotic and a member of the most widely used group of antibiotics. It has effects against many kinds of microorganisms. Although many types of bacteria are now resistant, penicillin is still one of the most useful antibiotics. Many kinds of adverse reactions to penicillin, such as interstitial nephritis, are well known; however, hemorrhagic cystitis is a very rare and obscure complication. To the best of our knowledge, there are only three previous reports of penicillin G-induced hemorrhagic cystitis in the English-language literature. We report herein a case of penicillin G-induced hemorrhagic cystitis and present a review of the literature. A 63-year-old woman was hospitalized because of a 2-day fever and right hip pain. She had undergone total right hip replacement arthroplasty 10 years previously. About 6 months previously, the artificial joint had been removed because of a prosthesis-related infection. At that time, she had received cefazolin and cefuroxime for each week. After Streptococcus dysgalactiae had been identified by polymerase chain reaction from infected tissue, penicillin (500 million units every 6 hours) and gentamicin were administered for 9 days. Because of peripheral phlebitis, the penicillin and gentamicin were changed to ceftriaxone. The patient recovered and was discharged after 1 week of ceftriaxone administration. The patient subsequently developed redness and mild tenderness on her right buttock and thigh. Laboratory findings revealed leukocytosis (white blood cell [WBC], 12,900/mm3) with a left shift and C-reactive protein (CRP) elevation. Hip magnetic resonance imaging revealed fluid collection around the previous operation site on the right hip and an enhancement in the bone marrow of the femur and soft tissues. These findings suggested septic arthritis and adjacent osteomyelitis. The patient underwent surgical drainage of the abscess of the hip joint and was empirically treated with vancomycin for 6 days. After penicillin-susceptible Streptococcus agalactiae had been isolated from the pus and tissue culture, vancomycin was changed to penicillin G. The administration of penicillin G (400 million units every 4 hours) was planned for 5 weeks. Her fever and CRP level declined soon after treatment was initiated. Frequent urination and dysuria developed suddenly on the 24th day of penicillin G use. Urinalysis showed mild pyuria (WBC, 10 to 19/high power field [HPF]) without bacteriuria or hematuria. The pyuria was considered to represent the development of the acute cystitis. Cefpodoxime was added, but her symptoms did not improve. Hematuria (red blood cell, > 100/HPF) developed and the pyuria (WBC, 30 to 49/HPF) increased in severity, and gross hematuria appeared after 7 days. Repeated urine cultures were negative. Cefpodoxime was changed to ciprofloxacin 6 days later, but there was no improvement, and the patient suffered continuously from frequency and dysuria. There was no fever, leukocytosis, or renal insufficiency. However, the CRP level increased slightly from 1.53 to 3.57 mg/dL, and the percentage of eosinophils in the peripheral blood increased dramatically from 0.5% to 18% on the 35th day of penicillin use. The patient had no previous history of drug allergies, including allergies to antibiotics. However, considering her overall clinical progression and long duration of penicillin use, penicillin-induced hemorrhagic cystitis was suspected. Penicillin G and ciprofloxacin were simultaneously discontinued on the 35th day. After stopping penicillin G, her frequency and dysuria improved dramatically within 2 days. The hematuria, pyuria, and eosinophilia also improved and were normalized in 8 days. Hemorrhagic cystitis is defined as a diffuse inflammatory condition of the urinary bladder and presents with lower urinary tract symptoms that include frequency, urgency, dysuria, and hematuria. It results from damage to the bladders transitional epithelium and blood vessels by toxins, pathogens, radiation, drugs, or disease. In most cases, drug-induced hemorrhagic cystitis resolves with discontinuation of the offending agent [1]. Penicillin G is reported to cause hemorrhagic cystitis on rare occasions. We used MEDLINE to retrieve previous reports of penicillin G induced hemorrhagic cystitis for all years and found three previous reports written in English. The clinical features of the three previous cases [2-4] and the present case are shown in Table 1. All previous cases were diagnosed with infective endocarditis, while our patient was diagnosed with relapsed bone and joint infection. The previous patients also underwent combination treatments with aminoglycosides for the initial 2 weeks. All patients developed the same bladder irritation symptoms such as dysuria, frequency, and gross hematuria, and two also suffered from back pain. The onset of these symptoms ranged from the 11th day to the 4th week after starting penicillin (median time, 20 days). In three cases including ours, urinalysis revealed pyuria, and urine culture was negative in all cases. Cystoscopy and bladder biopsy were performed in two cases; cystoscopy showed generally diffuse hemorrhagic cystitis, and biopsy revealed generalized inflammation with eosinophilic infiltration. Renal insufficiency (elevated serum creatinine level) was present in all cases excluding ours, and peripheral eosinophilia was present in all cases including ours. Interestingly, the urinary symptoms resolved promptly after discontinuing penicillin, and the laboratory findings returned to normal in 1 to 3 weeks in all cases. In one case [4], the patient underwent an abdominal computed tomography (CT) scan instead of cystoscopy and was found to have bilateral mild hydronephrosis and thickened bladder and ureteral walls. After stopping penicillin, the hydronephrosis and hydroureter also improved. The diagnosis in our case has the limitation that we did not carry out cystoscopy, bladder biopsy, or CT. However, the clinical presentation and laboratory abnormalities were very similar to those in the previous reports. In particular, the rapid resolution of symptoms and the clinical course of recovery after discontinuing penicillin G indicate that this case was another instance of penicillin G-induced hemorrhagic cystitis. Table 1 Clinical characteristics of patients with penicillin G-induced hemorrhagic cystitis The precise mechanism of penicillin-induced hemorrhagic cystitis is not known. It has been proposed that a penicillin-related immune reaction may damage the bladder mucosa or that penicillin itself or metabolites may be directly toxic to the bladder. Because most patients developed symptoms after prolonged exposure to penicillin, direct irritation of the bladder is a possibility. However, there is more evidence supporting an immunological basis. In three cases, peripheral eosinophilia developed, and two bladder biopsies revealed eosinophilic infiltration. In one study, a drug lymphocyte stimulation test for penicillin G was positive [4]. Moreover, immunoglobulins G and M and faint C3 deposition were seen in the bladder submucosa by immunofluorescence microscopy in the case of methicillin-induced hemorrhagic cystitis, which can be considered to involve the same mechanism as penicillin G [5]. Penicillin remains an important and useful antibiotic for the treatment of several infectious diseases. This case emphasizes that it is important to recognize hemorrhagic cystitis as an adverse reaction of penicillin because a high index of suspicion can lead to early diagnosis and withdrawal of the penicillin, without unnecessary examinations, and result in prompt recovery.

A Case of Acute Cerebral Aspergillosis Complicating Influenza A/H1N1pdm 2009

Invasive aspergillosis is a rare complication in patients with influenza infection. Several cases of invasive pulmonary aspergillosis accompanying influenza infections were reported during the influenza A/H1N1pdm 2009. We encountered a case of acute cerebral aspergillosis in a patient with influenza A/H1N1pdm 2009 infection. A 24-year-old man with uncontrolled diabetes was diagnosed with influenza A/H1N1pdm 2009 infection. Initial evaluation indicated methicillin-sensitive Staphylococcus aureus pneumonia and diabetic ketoacidosis along with influenza. During his hospital course, multiple new rim-enhancing mass lesions not evident in the initial evaluation developed in the fronto-parietal cortical and subcortical white matter and right cerebellum. Pathology and culture results confirmed the presence of Aspergillus fumigatus. Surgical drainage combined with a total of 18 weeks of antifungal therapy resulted in complete resolution of the infection. This case demonstrates that cerebral aspergillosis can present alongside influenza in patients with diabetes or those under intensive care. Clinical suspicion of invasive aspergillosis is required for a definite diagnosis and better prognosis in such cases.

Acute respiratory failure caused by phenytoin overdose.

To the Editor, Phenytoin is a commonly used antiepileptic drug despite its numerous adverse reactions, such as skin lesions, fever, and lymphadenopathy [1]. Most of the adverse reactions are extrapulmonary, and there have been few reports of acute pulmonary toxicity of the drug [2-4]. We present herein a case of acute bilateral pulmonary infiltration and respiratory failure due to phenytoin intoxication in a patient who attempted to commit suicide with about 50 phenytoin pills. A 49-year-old man was transferred to the emergency room in a comatose state. He had a history of temporal lobe epilepsy, major depressive disorder with three suicide attempts, and acquired immune deficiency syndrome. He had been taking phenytoin for about 1 year for epilepsy, and the antiretrovirals zidovudine, lamivudine, lopinavir, and ritonavir for 3 months. His latest CD4 count was 461/µL. Notably, 3 days before the event, the zidovudine had been changed to abacavir because of severe anemia characterized by a hemoglobin concentration of 4.0 g/dL, which had been considered to be a side effect of zidovudine. Because the patient could not afford to be hospitalized, a short-term outpatient departmental follow-up was arranged along with the replacement of zidovudine by abacavir. Despite the patients comatose status, his vital signs were all normal on the day of admission. Initial laboratory results were all within the normal range, with the exception of the above-mentioned severe anemia. However, his serum level of phenytoin was higher than 40 µg/mL (normal range, 10 to 18). Among the prescribed medications, namely lamivudine, abacavir, lopinavir, ritonavir, vitamin B, and vitamin C, there was no known drug interaction to blame for the increased level of serum phenytoin. As no abnormal findings were observed on a brain computed tomography scan, we suspected that his drowsiness was the result of phenytoin toxicity. On the second day after admission, the patient presented with fever and developed bilateral pulmonary infiltrates and, subsequently, respiratory failure, which led to intubation and transfer to the intensive care unit. Both his blood pressure and electrocardiography findings remained normal. All microbiology results were negative, including gram staining and culture, acid-fast staining and culture, Mycobacterium tuberculosis polymerase chain reaction (PCR), Pneumocystis jirovecii PCR and direct fluorescence antibody test, and fungal staining and culture. The hepatic enzymes aspartate aminotransferase and alanine aminotransferase were elevated at 1,664 and 1,068 IU/L, respectively. All other biochemical parameters, including bilirubin and alkaline phosphatase, were within their normal ranges. Cefotaxime and trimethoprim-sulfamethoxazole were empirically prescribed for possible pneumonia. Within a few days, the patients pulmonary infiltrates, level of consciousness, and elevation of aminotransferases markedly improved (Figs. 1 and ​and2).2). The serum level of phenytoin remained well above the limit of 40 µg/mL for the first 10 days of hospitalization, but declined thereafter. The patient confessed that he had taken about 50 phenytoin pills in a suicide attempt. He was successfully extubated and transferred to the general ward 5 days after admission. Antibiotics were discontinued, and lamivudine, abacavir, lopinavir, and ritonavir were resumed without recurrence of pulmonary infiltrates. Figure 1 (A) Chest radiograph on day of admission demonstrates no active lung lesion. (B) Chest radiograph on day 2 after admission shows diffuse airspace consolidation in both lungs

18 F-FDG PET and histopathologic findings in a patient with severe fever with thrombocytopenia syndrome

We report on a patient with severe fever with thrombocytopenia syndrome who fully recovered. Imaging with 2-deoxy-2-fluoro-glucose positron emission tomography showed hypermetabolism in regional lymph nodes and the spleen. Histopathological findings of affected lymph nodes showed subacute necrotizing lymphadenitis and the presence of virus-infected cells.

Sudden Deaths of Neonates Receiving Intravenous Infusion of Lipid Emulsion Contaminated with Citrobacter freundii.

At an intensive care unit, four neonates died consecutively within 80 minutes. Citrobacter freundii was isolated from blood samples of the 4 patients. It was also cultured from the leftover SMOFlipid that had been infused intravenously into the patients. In this in vitro study, we evaluated the bacterial growth kinetics and change in size of fat globules in SMOFlipid contaminated with C. freundii. Following the growth of bacteria, pH of SMOFlipid decreased to < 6, and the number of fat globules larger than 5 µm increased. Pulmonary fat embolism is proposed as a possible cause of the sudden deaths as well as fulminant sepsis.