Echinocandins as alternative treatment for HIV-infected patients with Pneumocystis pneumonia.

OBJECTIVES: Treatment with trimethoprim-sulfamethoxazole for Pneumocystis pneumonia (PCP) is often associated with adverse effects. Echinocandins, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, clinical experience with echinocandins in the treatment of PCP remains limited among HIV-infected patients. METHODS: From August 2013 to April 2018, data of HIV-infected patients with confirmed PCP who received echinocandins as alternative treatment because of intolerance or unresponsiveness to trimethoprim-sulfamethoxazole were retrospectively reviewed to assess the effectiveness and safety of echinocandins alone or in combination with other agents. RESULTS: In total, 34 patients were included, with a median CD4 count of 27 cells/µl [interquartile range (IQR), 20-93). Twenty-four patients (70.6%) presented with moderate-to-severe PCP. The most common adverse effects leading to withdrawal of trimethoprim-sulfamethoxazole were hepatotoxicity (29.4%), gastrointestinal upset (23.5%), and rash (17.6%). Nine patients (26.5%) were switched to echinocandins after failure of trimethoprim-sulfamethoxazole. The median interval before switch from trimethoprim-sulfamethoxazole to echinocandins was 9.0 days (IQR 5.0-14.0). The all-cause and PCP-related in-hospital mortality rate of patients receiving echinocandins as alternative therapy was 20.6% (7/34) and 14.7% (5/34), respectively. The all-cause in-hospital mortality was 0% in mild PCP cases and 29% (7/24) in moderate-to-severe PCP cases. Patients who had failed to respond to first-line trimethoprim-sulfamethoxazole treatment tended to have a higher in-hospital mortality rate than those without first-line trimethoprim-sulfamethoxazole failure (44.4% versus 12.0%, P = 0.06). CONCLUSION: Echinocandin therapy might serve as an alternative option for HIV-infected patients with PCP who are intolerable to trimethoprim-sulfamethoxazole.

Epidemiology and antifungal susceptibility of candidemia isolates of non-albicans Candida species from cancer patients.

Candidemia is a growing concern worldwide, and its species distribution has shifted toward non-albicans Candida in recent decades, especially in patients with malignancy. This study aimed to update the epidemiology and antifungal susceptibility of non-albicans candidemia isolates from the cancer patients. Adult cancer patients with non-albicans candidemia were recruited, and clinical data were retrospectively collected from five medical centers in Taiwan from 1 July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth dilution method using a Sensititre YeastOne system and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 346 episodes of non-albicans candidemia were identified in cancer patients. Candida tropicalis was the most common species (n=145, 41.9%) and had the highest resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates, including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher Charlson comorbidity index, non-albicans candidemia due to C. tropicalis, neutropenia and septic shock were independent predictors of 28-day mortality. In conclusion, the species distribution and antifungal susceptibility of non-albicans candidemia isolates in our study differed from those in Western countries, providing useful information about local epidemiology for the selection of empirical antifungal agents for cancer patients.

The experience of intramuscular benzathine penicillin for prophylaxis of recurrent cellulitis: A cohort study.

BACKGROUND/PURPOSE: Recurrent cellulitis is an important clinical issue but the optimal strategy for prophylaxis is not determined. Intramuscular benzathine penicillin at a 4-week interval had been adopted in our hospital and the study was conducted to evaluate the efficacy. METHODS: From January 1, 2009 to May 31, 2013, all patients aged ≥ 18 year, with a history of recurrent cellulitis and having received at least three shots of intramuscular benzathine penicillin for prophylaxis were retrospectively recruited for analysis. Two treatment periods (prophylaxis period and nonprophylaxis period) were defined. The effects of benzathine penicillin prophylaxis and patient characteristics on the incidence rate of recurrent cellulitis were analyzed using Poisson regression model. RESULTS: A total of 72 patients were enrolled, including 26 (36.1%) men. The most common underlying conditions were past surgery at the proximal side of the affected limb (38, 52.8%), malignancy (31, 43.1%), and diabetes mellitus (24, 33.3%). The incidence rate of recurrent cellulitis in the prophylaxis period was 0.73 episode/patient-year, significantly lower than that of 1.25 episodes/patient-year in the nonprophylaxis period (p < 0.001). Tinea pedis was a significant factor associated with increasing incidence of recurrent cellulitis in our cohort. CONCLUSION: Intramuscular benzathine penicillin at a 4-week interval may be an effective prophylactic strategy to reduce the incidence of cellulitis. Further studies are necessary to determine the factors associated with failure of prophylaxis as well as optimal individualized dosage and dosing interval of the prophylactic agent.

Changing epidemiology of candidemia in a medical center in middle Taiwan.

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. METHODS: Clinical and laboratory data from patients with candidemia were collected retrospectively at a tertiary medical center in Taiwan from July 1, 2009 to June 30, 2012 (a 36-month period). Demographics, clinical characteristics, and drug susceptibility of the invading Candida species of patients at the onset of candidemia were analyzed and compared with previous study from January 1, 2001 to June 30, 2003 (a 30-month period). RESULTS: A total of 209 episodes of candidemia in 205 patients were identified in this study period. When compared with the previous study period, more patients were admitted for medical conditions at percentages ranging from 49.5% to 69.8%; the incidence rate of health care-associated candidemia increased from 0.76 to 1.14 per 1000 discharges; the proportion of Candida albicans in patients with candidemia decreased from 64.8% to 43.6% whereas the proportion of Candida glabrata increased greatly from 1.1% to 21.6% and the proportions of Candida tropicalis and Candida parapsilosis were slightly elevated (19.8-22.0% and 2.2-7.3%, respectively). All of the C. albicans isolates remained susceptible to fluconazole, whereas 66.7% of C. glabrata isolates were dose-dependent susceptible, and 4.4% of C. glabrata isolates and 11.6% C. tropicalis isolates were resistant. There was one C. glabrata and one Candida guilliermondii resistant to echinocandin. The predictors for 30-day mortality included the high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, use of parenteral nutrition, underlying malignancy, liver cirrhosis, and neutropenia whereas candidemia by C. parapsilosis or C. glabrata is a favorable predictor when compared with C. albicans. CONCLUSION: The distribution of Candida species in candidemia was changed. Although C. albicans remained the major species, the isolation of non-C. albicans spp., especially C. glabrata, increased. Patients with candidemia still had high mortalities due to severity of illness and underlying conditions.

Multicenter study of trimethoprim/sulfamethoxazole-related hepatotoxicity: incidence and associated factors among HIV-infected patients treated for Pneumocystis jirovecii pneumonia.

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Whole-genome sequencing and identification of Morganella morganii KT pathogenicity-related genes.

BACKGROUND: The opportunistic enterobacterium, Morganella morganii, which can cause bacteraemia, is the ninth most prevalent cause of clinical infections in patients at Changhua Christian Hospital, Taiwan. The KT strain of M. morganii was isolated during postoperative care of a cancer patient with a gallbladder stone who developed sepsis caused by bacteraemia. M. morganii is sometimes encountered in nosocomial settings and has been causally linked to catheter-associated bacteriuria, complex infections of the urinary and/or hepatobiliary tracts, wound infection, and septicaemia. M. morganii infection is associated with a high mortality rate, although most patients respond well to appropriate antibiotic therapy. To obtain insights into the genome biology of M. morganii and the mechanisms underlying its pathogenicity, we used Illumina technology to sequence the genome of the KT strain and compared its sequence with the genome sequences of related bacteria. RESULTS: The 3,826,919-bp sequence contained in 58 contigs has a GC content of 51.15% and includes 3,565 protein-coding sequences, 72 tRNA genes, and 10 rRNA genes. The pathogenicity-related genes encode determinants of drug resistance, fimbrial adhesins, an IgA protease, haemolysins, ureases, and insecticidal and apoptotic toxins as well as proteins found in flagellae, the iron acquisition system, a type-3 secretion system (T3SS), and several two-component systems. Comparison with 14 genome sequences from other members of Enterobacteriaceae revealed different degrees of similarity to several systems found in M. morganii. The most striking similarities were found in the IS4 family of transposases, insecticidal toxins, T3SS components, and proteins required for ethanolamine use (eut operon) and cobalamin (vitamin B12) biosynthesis. The eut operon and the gene cluster for cobalamin biosynthesis are not present in the other Proteeae genomes analysed. Moreover, organisation of the 19 genes of the eut operon differs from that found in the other non-Proteeae enterobacterial genomes. CONCLUSIONS: This is the first genome sequence of M. morganii, which is a clinically relevant pathogen. Comparative genome analysis revealed several pathogenicity-related genes and novel genes not found in the genomes of other members of Proteeae. Thus, the genome sequence of M. morganii provides important information concerning virulence and determinants of fitness in this pathogen.

"Cough officer screening" improves detection of pulmonary tuberculosis in hospital in-patients.

BACKGROUND: Current tuberculosis (TB) reporting protocols are insufficient to achieve the goals established by the Stop TB partnership. Some countries have recommended implementation of active case finding program. We assessed the effect of Cough Officer Screening (an active screening system) on the rate of TB detection and health care system delays over the course of four years. METHODS: Patients who were hospitalized at the Changhua Christian Hospital (Changhua, Taiwan) were enrolled from September 2004 to July 2006 (Stage I) and August 2006 to August 2008 (Stage II). Stage II was implemented after a Plan-Do-Check-Act (PDCA) cycle analysis indicated that we should exclude ICU and paediatric patients. RESULTS: In Stage I, our COS system alerted physicians to 19,836 patients, and 7,998 were examined. 184 of these 7,998 patients (2.3%) had TB. Among these 184 patients, 142 (77.2%) were examined for TB before COS alarming and 42 were diagnosed after COS alarming. In Stage II, a total of 11,323 patients were alerted by the COS system. Among them, 6,221 patients were examined by physicians, and 125 of these patients (2.0%) had TB. Among these 125 patients, 113 (90.4%) were examined for TB before COS alarming and 12 were diagnosed after COS alarming. The median time from COS alarm to clinical action was significantly less (p = 0.041) for Stage I (1 day; range: 0-16 days) than for Stage II (2 days; range: 0-10 days). CONCLUSION: Our COS system improves detection of TB by reducing the delay from infection to diagnosis. Modifications of scope may be needed to improve cost-effectiveness.

Risk factors for candidemia-related mortality at a medical center in central Taiwan.

BACKGROUND AND PURPOSE: Bloodstream infections due to Candida spp. are associated with significant mortality and morbidity. This study analysed the epidemiology and outcome of candidemia cases in a teaching hospital in central Taiwan. METHODS: We retrospectively studied the clinical characteristics and antifungal susceptibility of isolates and risk factors for mortality in 91 cases of candidemia treated from January 1, 2001 to June 30, 2003. RESULTS: The mean age of the patients was 67 years (range, 30-90 years). Three episodes (3%) were community acquired. Adequate antifungal therapy was given to 78 patients (78%). Cancer (38.5%) and diabetes mellitus (36.3%) were the 2 most common underlying diseases. The most frequent risk factors identified for candidemia were prior broad-spectrum antibiotic use (84.6%), central venous catheterization (83.5%) and Candida colonization (79.5%). The most frequent isolates were Candida albicans (64.8%) and Candida tropicalis (19.8%). All of the C. albicans and C. tropicalis isolates were sensitive to fluconazole (minimal inhibitory concentration