AIDS-related opportunistic illnesses and early initiation of HIV care remain critical in the contemporary HAART era: a retrospective cohort study in Taiwan.

BACKGROUND: No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). METHODS: Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. RESULTS: Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/µL experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOIs (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/µL at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12.59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64). CONCLUSIONS: Despite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.

Incidence rates of tuberculosis in chronic hepatitis C infected patients with or without interferon based therapy: a population-based cohort study in Taiwan.

BACKGROUND: It is debated whether interferon-based therapy (IBT) would affect the incidence of active tuberculosis (TB) among hepatitis C virus (HCV) infected patients. Although some case reports have demonstrated a possible association, the results are currently inconclusive. Therefore, we conducted a nation-wide population study to investigate the incidence of active TB in HCV infected patients receiving IBT in Taiwan. METHODS: This 9-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 ( >23.7 million). This insurance program covers all citizens in Taiwan. We conducted a retrospective cohort study that identified subjects with HCV infection. IBTs were defined as regimens that included interferon α, peginterferon α2a and peginterferon α2b for at least 2 months. Among them, 621 subjects received IBT, and 2,460 age- and gender-matched subjects were enrolled for analysis. The Cox proportional hazards models were used to estimate the hazard ratio (HR) for active TB, and associated confidence intervals (CIs), comparing IBT cohort and untreated cohort. The endpoint in this study was whether an enrolled subject had a new diagnosis of active TB. RESULTS: During the 9-year enrollment period, the treated and untreated cohorts were followed for a mean (± SD) duration of 6.97 ± 0.02 years and 8.21 ± 0.01 years, respectively. The cumulative incidence rate of active TB during this study period was 0.150 and 0.151 per 100 person-years in the IBT treated and untreated cohorts, respectively. There was no significant difference in the incidence of active TB in either cohort during a 1-year follow-up (Adjusted Hazard Ratio (AHR): 2.81, 95% Confidence Interval (95% CI): 0.61-12.98) or the long-term follow-up (AHR: 1.02, 95% CI: 0.28-3.78). The Cox proportional hazards model demonstrated that IBT was not a risk factor for active TB . The only risk factor for active TB was the occurrence of hepatic encephalopathy. CONCLUSION: Our results showed that IBT is associated with increased hazard of active TB in HCV infected patients in 1-year follow-up; however, the effect sizes were not statistically significant.

Klebsiella pneumoniae bacteremia and renosplenic abscesses without intestinal symptoms as the initial manifestations of non-steroidal anti-inflammatory drug-induced colitis: a rare case report.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely prescribed drugs in the world, can cause gastrointestinal damage, including colitis. However, the prevalence of NSAID-induced colitis is unknown because the disease is often asymptomatic. CASE PRESENTATION: We report the case of a 64-year-old female patient with a history of long-term NSAID use, who was hospitalized with septic shock caused by Klebsiella pneumoniae bacteremia. Computed tomography revealed multiple renal and splenic abscesses with diffuse colon wall thickening. A colonoscopy confirmed colitis with diffuse ulcers. NSAIDs were discontinued after this hospitalization. The abscesses improved after antibiotic treatment. A short course of balsalazide treatment was given under the suspicion of ulcerative colitis. Balsalazide was discontinued four months later due to a non-compatible clinical course. A follow-up colonoscopy two years later revealed a normal colon mucosa, and NSAID-induced colitis was diagnosed. CONCLUSION: This is the first reported case of combined bacterial splenic and renal abscesses without intestinal manifestations as the initial presentation of NSAID-induced colitis. In contrast to cases of K. pneumoniae bacteremia with primary liver abscesses in patients with diabetes mellitus in Taiwan, we presented the first case with abscesses caused by community-acquired K. pneumoniae in the kidneys and spleen without liver invasion. In conclusion, our case report alerts clinicians to the possibility that K. pneumoniae bacteremia combined with multiple abscesses can be associated with severe NSAID-induced colitis.

A mucormycosis case in a cirrhotic patient successfully treated with posaconazole and review of published literature.

Mucormycosis is an invasive fungal infection associated with a high mortality rate, especially in immunocompromised hosts. Mucormycosis rarely occurs in cirrhotic patients. Here, we report a case of mucormycosis with underlying liver cirrhosis and diabetes mellitus. The patient suffered from maxillary sinusitis and osteomyelitis, and the infection was successfully treated with antifungal agents, surgical debridement, and hyperbaric oxygen therapy. The antifungal treatments used were liposomal amphotericin B, itraconazole, and posaconazole. Although our patient had liver cirrhosis (Child-Pugh classification B), no hepatic decompensation was developed during the treatment course of posaconazole. This is the first report of the safe and effective use of posaconazole for the treatment of mucormycosis in a cirrhotic patient.

Isolation of Streptococcus bovis from apheresis platelets of asymptomatic donor warranted colonoscopy investigation: case report and literature review.

BACKGROUND: Bacterial contamination of platelet (PLT) products is one of the most serious complications of transfusion. Culturing PLT components may detect the presence of bacteria, thus reducing the risk of a septic result after transfusion. Streptococcus bovis has previously been reported as a contaminating microorganism in PLT products. Here we report an asymptomatic donor diagnosed with occult colon malignancy after positive isolation of S. bovis from his apheresis PLTs (APs). We also review previous cases. CASE REPORT: The PLT donor was a 50-year-old man with more than 150 prior plateletpheresis or whole blood donations. Bacterial culture of his AP components yielded two positive results: group D Streptococcus was isolated in July 2008 and S. bovis was reported in April 2010. The donor received further testing, and colonofibroscopic examination revealed colonic neoplasm. Pathologic examination of the biopsied tissue led to a diagnosis of invasive adenocarcinoma. He underwent a left hemicolectomy in July 2010. Examination of the resection specimen confirmed adenocarcinoma, Stage III with regional lymph node metastatic adenocarcinoma. CONCLUSION: Donated AP products positive for S. bovis should not be presumed to be due to contamination during collection. This bacteremia originating from donor factors needs to be carefully evaluated. Colonofibroscopic examination is recommended for these donors to detect colonic malignancy as early as possible.

Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) is a growing and serious nosocomial infection worldwide, such that developing new agents against it is critical. The antimicrobial activities of the rhizomes from Zingiber officinale, known as ginger, have not been proven in clinical bacterial isolates with extensive drug-resistance. This study aimed to investigate the effects of four known components of ginger, [6]-dehydrogingerdione, [10]-gingerol, [6]-shogaol and [6]-gingerol, against clinical XDRAB. All these compounds showed antibacterial effects against XDRAB. Combined with tetracycline, they showed good resistance modifying effects to modulate tetracycline resistance. Using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method, these four ginger compounds demonstrated antioxidant properties, which were inhibited by MnO2, an oxidant without antibacterial effects. After the antioxidant property was blocked, their antimicrobial effects were abolished significantly. These results indicate that ginger compounds have antioxidant effects that partially contribute to their antimicrobial activity and are candidates for use in the treatment of infections with XDRAB.

Why is in-hospital diagnosis of pulmonary tuberculosis delayed in southern Taiwan?

BACKGROUND/PURPOSE: In-hospital diagnosis delay (IHDD) of pulmonary tuberculosis (TB) has a significant impact on nosocomial TB transmission. We investigated the risk factors associated with prolonged IHDD in Taiwan, a high-resource, mid-incidence area. METHODS: Between January 2005 and August 2006, we retrospectively enrolled 193 consecutive hospitalized patients. All of them had culture-proven pulmonary TB and did not receive antitubercular treatment at admission. IHDD was defined as the interval between admission and initiation of antitubercular treatment. Patients were grouped according to the median value of IHDD. RESULTS: The median IHDD was 7 days. Patients with IHDD > 7 days were considered the prolonged-delay group, and those with IHDD 65 years [3.19 (1.01-10.05), p = 0.048]. Death attributed to tuberculosis was associated with positive sputum smear (hazard ratio = 21.85; 95% CI = 2.74-174.44; p = 0.004) but not prolonged IHDD (p = 0.325). CONCLUSION: To minimize IHDD, clinicians should carefully manage hospitalized patients with risk factors for prolonged delay, such as those with negative sputum smears, non-cavitary lesions on chest radiographs, admission to departments other than chest medicine/infectious diseases, exposure to fluoroquinolones before antitubercular treatment, underlying malignancy, and age > 65 years.

Sphingomonas paucimobilis bacteraemia and septic arthritis in a diabetic patient presenting with septic pulmonary emboli.

Sphingomonas paucimobilis, a yellow-pigmented, aerobic, glucose non-fermenting, Gram-negative bacillus, is a rare cause of human infection normally associated with immunocompromised hosts. We report a case of bacteraemia and septic arthritis in a 47-year-old diabetic man who presented with septic pulmonary emboli due to S. paucimobilis. The patient had an initial presentation of fever, right knee pain, coughing, dyspnoea and chest pain. The infection was treated successfully by surgical debridement combined with meropenem plus ciprofloxacin, based on the patient's antibiotic susceptibility profile. To our knowledge, this is the first case report for septic pulmonary emboli having arisen from an S. paucimobilis infection.

Rifampin-associated pseudomembranous colitis.

Pseudomembranous colitis (PMC) is known to develop after antibiotic treatment, but is rarely associated with antituberculosis (anti-TB) agents. We report a 28-year-old woman without underlying diseases developing PMC after 126 days of anti-TB treatment. Severe diarrhea and abdominal cramping pain were experienced. Colonoscopic biopsy proved the diagnosis of PMC. Her symptoms improved after discontinuing the anti-TB agents but recurred shortly after challenging with rifampin and isoniazid. Metronidazole administration and replacement of rifampin with levofloxacin successfully cured the PMC. Our report supports the notion that rifampin can induce PMC.

Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.

BACKGROUND/PURPOSE: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. METHODS: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. RESULTS: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). CONCLUSION: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.

Immunoproteomic identification of the hypothetical protein NMB1468 as a novel lipoprotein ubiquitous in Neisseria meningitidis with vaccine potential.

Many potential vaccine candidates for serogroup B Neisseria meningitidis (NMB) have been identified by reverse vaccinology, a genome-based approach. However, some candidates may be unseen owing to uncertain annotation or their peculiar properties. In this study, we describe the preparation and identification of a novel lipoprotein expressed in all meningococcal strains tested. mAb were first prepared from mice immunized with a meningococcal B strain isolated in Taiwan. Total proteins from the immunizing strain were separated by 2-DE in duplicate. Clone 4-7-3, which crossreacted to 174 tested meningococcal isolates, was used as the primary antibody for Western blotting. The immunoreactive spot was identified by LC-mass spectrometric analysis of the corresponding spot from the silver-stained gel and confirmed by molecular biology approach to be a novel lipoprotein encoded by the hypothetical NMB1468 gene. The potential use of this protein, designated Ag473/NMB1468, as a vaccine component was evaluated using the recombinant protein produced in Escherichia coli. Immunized mice were found to be protected from developing meningococcal disease after intraperitoneal inoculation with a lethal dose of meningococcal strain Nm22209, suggesting that Ag473/NMB1468 may be a promising vaccine candidate. This study also demonstrates the usefulness of the immunoproteomic approach in identification of novel vaccine candidates.

The high prevalence of Legionella pneumophila contamination in hospital potable water systems in Taiwan: implications for hospital infection control in Asia.

BACKGROUND: The major sources of Legionnaires' disease (LD) are the potable water systems of large buildings including hospitals, nursing homes, and hotels. Culturing the hospital water system for Legionella allows a preventive approach for hospital-acquired LD. However, hospital-acquired LD is rarely reported in Taiwan, and environmental cultures of Legionella in hospital water systems in Taiwan have never been systematically performed. OBJECTIVE: The objective of this study was to determine if Legionella is present in hospital water systems in Taiwan. Water quality analysis was also performed to determine if geographic differences in water quality result in different Legionella positivity rates. METHOD: The water systems of 16 hospitals throughout Taiwan were tested for Legionella by culture. Standardized culture procedures were followed. RESULTS: Legionella pneumophila was isolated from 63% (10/16) of the hospital water systems; 19% (3/16) of the hospitals had an L. pneumophila positive rate greater than 30%. L. pneumophila serogroups 1 and 6 (strains that are most responsible for Legionella infections) were isolated from 80% (8/10) and 60% (6/10), respectively, of the hospitals that yielded L. pneumophila in their water distribution systems. CONCLUSION: As was shown in epidemiological studies in the USA and Spain, hospital-acquired legionellosis may be prevalent but underdiagnosed in Taiwan.

Risk factors of ciprofloxacin resistance in urinary Escherichia coli isolates.

BACKGROUND AND PURPOSE: Increasing rates of fluoroquinolone resistance among Escherichia coli have been reported in Taiwan and worldwide. We aimed to identify the risk factors of ciprofloxacin resistance in urinary E. coli isolates. METHODS: Patients with positive urine culture result for E. coli and resistance to ciprofloxacin between September 1, 1999 and December 31, 1999 were prospectively identified as cases, and compared with ciprofloxacin-susceptible E. coli isolates (controls). THE CASE: control ratio was 1:2. Data were collected with standardized case record forms. RESULTS: Sixty one cases and 122 controls were compared. Multivariate analysis indicated that urinary tract catheterization (odds ratio [OR] = 2.631, 95% confidence interval [CI] = 1.058-6.544; p=0.037) and prior exposure to quinolones (OR = 13.072, 95% CI = 3.367-50.75; p<0.001) were independent risk factors for ciprofloxacin resistance in urinary E. coli isolates. Compared with ciprofloxacin-susceptible E. coli isolates, ciprofloxacin-resistant E. coli isolates from urine specimens had a significantly higher rate of resistance to all other tested antimicrobial agents, except amikacin and imipenem. CONCLUSION: In patients with urinary tract infection, urinary catheterization and prior quinolone exposure are associated with a high risk of ciprofloxacin-resistant E. coli which may cause treatment failure.

Hemorrhagic bullae caused by Bacteroides fragilis in a patient with intra-abdominal infection.

Skin manifestations due to intra-abdominal infection are uncommon but could be a warning sign of severe infection. We report a 58-year-old uremic female who had acute cholecystitis and pneumatosis intestinalis. She developed periumbilical hemorrhagic bullae and finally had a fatal outcome with medical therapy. Severe intra-abdominal infection such as pneumatosis intestinalis should be suspected when periumbilical bullae increase in size.

The epidemiology, antibiograms and predictors of mortality among critically-ill patients with central line-associated bloodstream infections.

BACKGROUND/PURPOSE: For high risk of central line-associated bloodstream infections (CLABSIs) in patients of intensive care units (ICUs) and scarcely epidemiology and therapeutic recommendations in Asia, we aimed to evaluate the annual change in epidemiology, antibiogram, and risk factors for 14-day mortality. METHODS: A retrospective study of ICUs patients with CLABSIs at a medical center in Taiwan (2010-2016), where central line care bundle implemented since 2014, by reviewing clinical data, pathogens, and the antibiogram. RESULTS: Gram-negative bacteria (59.3%) were main microorganisms of CLABSIs, and 9.0% of all GNB were MDROs. Acinetobacter spp., Enterobacter spp., and Stenotrophomonas maltophilia were the most frequently isolated. In multivariate analysis, malignancy, inadequate empirical antimicrobial therapy, inadequate definite antimicrobial therapy, and infection by fungi or multidrug-resistant organisms (MDROs) were associated with 14-day mortality (all p < 0.05). The CLABSI incidence rate decreased from 5.54 to 2.18 per 1000 catheter-day (from 2014 to 2015) with improved compliance to care bundle. Carbapenem and aminoglycoside were suitable empirical drugs in the hospital setting when GNB is predominant for CLABSI. Significant decreasing susceptibility of ampicillin/sulbactam in Enterobacter spp. (36.7%-0.0%), and ampicillin/sulbactam (12.5%-0.0%), ceftazidime (100.0%-52.9%), and tigecycline (87.5%-35.3%) in Serratia marcescens. CONCLUSION: We identified Gram-negative bacteria as leading pathogens of CLABSIs in a Taiwan medical center, and good compliance to care bundle is associated with reduced CLABSI incidence rate. Malignancy, infection by MDROs or fungi, inadequate empirical or definite antimicrobial therapy are significant factors for 14-day mortality.

Cellulitis and bacteremia caused by Bergeyella zoohelcum.

Bergeyella zoohelcum is a rod-shaped, aerobic, Gram-negative, non-motile and non-saccharolytic bacterium. It is frequently isolated from the upper respiratory tract of dogs, cats and other mammals. Clinically, B. zoohelcum has been known to cause cellulitis, leg abscess, tenosynovitis, septicemia, pneumonia and meningitis, and is associated with animal bites. In addition, food-borne transmission was considered in a recent case report. We report a 73-year-old man with liver cirrhosis who had no history of dog bite but had dog exposure, who developed cellulitis of the left lower leg and B. zoohelcum was isolated from blood culture. This patient, without evidence of polymicrobial infection, was treated with cefazolin and gentamicin with a good outcome. B. zoohelcum is a zoonotic pathogen that may cause bacteremia in patients with underlying disease such as liver cirrhosis; it can be treated with a beta-lactam or quinolone.

Cat scratch disease from a domestic dog.

Cat scratch disease (CSD), caused by Bartonella henselae, is a zoonosis and characterized by self-limited lymphadenopathy. It is transmitted commonly by scratch or bite from cats or kitten. We report an unusual case of CSD caused by a domestic dog scratch that we believe is the first report in Taiwan. A 23-year-old healthy woman developed cervical lymphadenopathy, mild fever, headache, and malaise 3 days after dog scratch. Her symptoms improved after azithromycin treatment. Serology proved B. henselae infection. The owners of a domestic dog might be at risk of "cat" scratch disease.

Melioidosis presenting with isolated splenic abscesses: a case report.

Splenic abscesses caused by Burkholderia pseudomallei are rarely reported in Taiwan. Here we report a middle-aged man who presented with fever, chills, and general malaise for several days. Abdominal echo revealed isolated splenic abscesses and he received antibiotics treatment according to the initial blood culture result, Serratia marcescens. However, fever did not subside. Then he was referred to our hospital and meropenem was prescribed. Fever subsided 5 days after the beginning of meropenem administration. Repeated fine-needle aspiration of splenic abscesses drained out the pus, which was cultured as B. pseudomallei. He was finally diagnosed as a case of melioidosis based on microbiological evidence. Physicians must take melioidosis into consideration when splenic abscesses are encountered clinically.

Identification of factors for physicians to facilitate early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever in Taiwan.

BACKGROUND: Dengue fever, rickettsial diseases, and Q fever are acute febrile illnesses with similar manifestations in tropical areas. Early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever may be made by understanding the distinguishing clinical characteristics and the significance of demographic and weather factors. METHODS: We conducted a retrospective study to identify clinical, demographic, and meteorological characteristics of 454 dengue fever, 178 scrub typhus, 143 Q fever, and 81 murine typhus cases in three Taiwan hospitals. RESULTS: Case numbers of murine typhus and Q fever correlated significantly with temperature and rainfall; the scrub typhus case number was only significantly related with temperature. Neither temperature nor rainfall correlated with the case number of dengue fever. The rarity of dengue fever cases from January to June in Taiwan may be a helpful clue for diagnosis in the area. A male predominance was observed, as the male-to-female rate was 2.1 for murine typhus and 7.4 for Q fever. Multivariate analysis revealed the following six important factors for differentiating the rickettsial diseases and Q fever group from the dengue fever group: fever ≥8 days, alanine aminotransferase > aspartate aminotransferase, platelets >63,000/mL, C-reactive protein >31.9 mg/L, absence of bone pain, and absence of a bleeding syndrome. CONCLUSION: Understanding the rarity of dengue in the first half of a year in Taiwan and the six differentiating factors may help facilitate the early differential diagnosis of rickettsial diseases and Q fever from dengue fever, permitting early antibiotic treatment.