Efficacy and safety of switching from nevirapine immediate-release twice daily to nevirapine extended-release once daily in virologically suppressed HIV-infected patients: a retrospective cohort study in Taiwan.

BACKGROUND: Whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from nevirapine immediate-release (NVP-IR) to NVP extended-release (NVP-XR) demonstrated in the TRANxITION study conducted in Europe and North America are also applicable to virologically suppressed HIV-infected Taiwanese patients remains unknown. We evaluated the comparative safety and efficacy of continuing NVP-IR versus switching to NVP-XR in virologically suppressed HIV-infected Taiwanese adults receiving combined antiretroviral therapy (cART) regimens. METHODS: We conducted a retrospective cohort study at Kaohsiung Veterans General Hospital from April 1, 2013, to March 31, 2015. Eighty-four virologically suppressed HIV-infected adults receiving NVP-IR cART were split into two groups: those continuing with NVP-IR (n = 49) and those being switched to NVP-XR (n = 35). Demographic characteristics, clinical variables, and laboratory findings were compared. Therapeutic drug monitoring of steady-state plasma NVP concentrations and genotype analysis of CYP2B6 516 were also performed in 22 participants. The primary endpoint was continued virological suppression at the end of the study. Secondary endpoints were time to loss of virological response and adverse events. RESULTS: During a mean follow-up of 18.4 months, the NVP-XR group demonstrated similar success at maintaining virological response compared with the NVP-IR group (82.9% vs. 85.7%; P = 0.72). Cox regression analysis indicated that there were no significant differences between NVP regimens for time to loss of virological response (hazard ratio: 0.940; P = 0.754). Furthermore, there were no significant differences in adverse events between these two groups. In the 22 participants, there was a non-significantly lower level of steady-state plasma NVP concentrations in the NVP-XR group than in NVP-IR recipients (5145.0 ng/mL vs. 6775.0 ng/mL; P = 0.267). The prevalence of CYP2B6 516 GT was 86.6%, and there was no significant difference in the distribution of CYP2B6 516 between these two groups. CONCLUSIONS: We found that switching from NVP-IR to NVP-XR appeared to have similar safety and efficacy compared with continuing NVP-IR among virologically suppressed, HIV-infected Taiwanese patients. Our finding of higher Ctrough levels in both groups compared with other studies conducted in Caucasian populations and the high prevalence of CYP2B6 516 GT requires further investigation in a larger Taiwanese cohort.

Development of a prediction model for bacteremia in hospitalized adults with cellulitis to aid in the efficient use of blood cultures: a retrospective cohort study.

BACKGROUND: Cellulitis is a common infectious disease. Although blood culture is frequently used in the diagnosis and subsequent treatment of cellulitis, it is a contentious diagnostic test. To help clinicians determine which patients should undergo blood culture for the management of cellulitis, a diagnostic scoring system referred to as the Bacteremia Score of Cellulitis was developed. METHODS: Univariable and multivariable logistic regression analyses were performed as part of a retrospective cohort study of all adults diagnosed with cellulitis in a tertiary teaching hospital in Taiwan in 2013. Patients who underwent blood culture were used to develop a diagnostic prediction model where the main outcome measures were true bacteremia in cellulitis cases. Area under the receiver operating characteristics curve (AUC) was used to demonstrate the predictive power of the model, and bootstrapping was then used to validate the performance. RESULTS: Three hundred fifty one cases with cellulitis who underwent blood culture were enrolled. The overall prevalence of true bacteremia was 33/351 cases (9.4 %). Multivariable logistic regression analysis showed optimal diagnostic discrimination for the combination of age ≥65 years (odds ratio [OR] = 3.9; 95 % confidence interval (CI), 1.5-10.1), involvement of non-lower extremities (OR = 4.0; 95 % CI, 1.5-10.6), liver cirrhosis (OR = 6.8; 95 % CI, 1.8-25.3), and systemic inflammatory response syndrome (SIRS) (OR = 15.2; 95 % CI, 4.8-48.0). These four independent factors were included in the initial formula, and the AUC for this combination of factors was 0.867 (95 % CI, 0.806-0.928). The rounded formula was 1 × (age ≥65 years) + 1.5 × (involvement of non-lower extremities) + 2 × (liver cirrhosis) + 2.5 × (SIRS). The overall prevalence of true bacteremia (9.4 %) in this study could be lowered to 1.0 % (low risk group, score ≤1.5) or raised to 14.7 % (medium risk group, score 2-3.5) and 41.2 % (high risk group, score ≥4.0), depending on different clinical scores. CONCLUSIONS: Determining the risk of bacteremia in patients with cellulitis will allow a more efficient use of blood cultures in the diagnosis and treatment of this condition. External validation of this preliminary scoring system in future trials is needed to optimize the test.

High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS.

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the most effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS. The major drawback is the frequent occurrence of adverse reactions (ADRs).The current study was designed to determine the frequency and risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS. METHODS: A retrospective study was conducted in adult patients with PJP and AIDS who were admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January 2006 and December 2011. Charts were reviewed to determine the effect of age, risk behaviors, severity of illness, viral load, CD4 cell counts, use of corticosteroids, and dosage and duration of TMP/SMX on ADRs during hospitalization. Patients who received TMP/SMX for ≤ 5 days or with an incomplete medical record were excluded. Multivariate logistic regression was used to calculate the hazard ratio (HR) for ADRs. RESULTS: Fifty two of 75 patients with PJP and AIDS met the study criteria. Of these patients, 21/52 (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms in three (14.3%). Most of the ADRs occurred within the 1(st) 2 weeks of TMP/SMX therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX of ≥ 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40-10.35; p = 0.009) and age 34 years (HR, 4.30; 95% confidence interval, 1.52-12.14; p = 0.006) were independently associated with ADRs. CONCLUSION: We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

Clinical and microbiological characteristics of purulent and non-purulent cellulitis in hospitalized Taiwanese adults in the era of community-associated methicillin-resistant Staphylococcus aureus.

BACKGROUND: The risk factors, microbial etiology, differentiation, and clinical features of purulent and non-purulent cellulitis are not well defined in Taiwan. METHODS: We conducted a retrospective cohort study of hospitalized adults with cellulitis in Taiwan in 2013. The demographic characteristics, underlying diseases, clinical manifestations, laboratory and microbiological findings, treatments, and outcomes were compared for patients with purulent and non-purulent cellulitis. RESULTS: Of the 465 patients, 369 had non-purulent cellulitis and 96 had purulent cellulitis. The non-purulent group was significantly older (p = 0.001) and was more likely to have lower limb involvement (p < 0.001), tinea pedis (p = 0.003), stasis dermatitis (p = 0.025), a higher Charlson comorbidity score (p = 0.03), and recurrence at 6 months post-infection (p = 0.001) than the purulent group. The purulent group was more likely to have a wound (p < 0.001) and a longer hospital stay (p = 0.001) and duration of antimicrobial therapy (p = 0.003) than the non-purulent group. The etiological agent was identified in 35.5 % of the non-purulent cases, with ß-hemolytic streptococci the most frequent cause (70.2 %). The etiological agent was identified in 83.3 % of the purulent cases, with Staphylococcus aureus the predominant pathogen (60 %): 50 % of these were methicillin-resistant S. aureus (MRSA). In multivariable analysis, purulent group (odds ratio (OR), 5.188; 95 % confidence interval (CI), 1.995-13.493; p = 0.001) was a positive predictor of MRSA. The prescribed antimicrobial agents were significantly different between the purulent and non-purulent groups, with penicillin the most frequently used antimicrobial agent in the non-purulent group (35.2 %), and oxacillin the most frequent in the purulent group (39.6 %). The appropriate antimicrobial agent was more frequently prescribed in the non-purulent group than in the purulent group (83.2 % vs. 53.8 %, p < 0.001). CONCLUSIONS: The epidemiology, clinical features, and microbiology of purulent and non-purulent cellulitis were significantly different in hospitalized Taiwanese adults. Purulence was a positive predictor of MRSA as the causal agent of cellulitis. These findings provide added support for the adoption of the IDSA guidelines for empirical antimicrobial therapy of cellulitis in Taiwan.

Emergence of sporadic non-clustered cases of hospital-associated listeriosis among immunocompromised adults in southern Taiwan from 1992 to 2013: effect of precipitating immunosuppressive agents.

BACKGROUND: Sporadic non-clustered hospital-associated listeriosis is an emerging infectious disease in immunocompromised hosts. The current study was designed to determine the impact of long-term and precipitating immunosuppressive agents and underlying diseases on triggering the expression of the disease, and to compare the clinical features and outcome of hospital-associated and community-associated listeriosis. METHODS: We reviewed the medical records of all patients with Listeria monocytogenes isolated from sterile body sites at a large medical center in southern Taiwan during 1992-2013. Non-clustered cases were defined as those unrelated to any other in time or place. Multivariable regression analysis was used to determine factors associated with prognosis. RESULTS: Thirty-five non-clustered cases of listeriosis were identified. Twelve (34.2%) were hospital-associated, and 23 (65.7%) were community-associated. The 60-day mortality was significantly greater in hospital-associated than in community-associated cases (66.7% vs. 17.4%, p = 0.007). Significantly more hospital-associated than community-associated cases were treated with a precipitating immunosuppressive agent within 4 weeks prior to onset of listeriosis (91.7% vs. 4.3%, respectively p < 0.001). The median period from the start of precipitating immunosuppressive treatment to the onset of listeriosis-related symptoms was 12 days (range, 4-27 days) in 11 of the 12 hospital-associated cases. In the multivariable analysis, APACHE II score >21 (p = 0.04) and receipt of precipitating immunosuppressive therapy (p = 0.02) were independent risk factors for 60-day mortality. CONCLUSIONS: Sporadic non-clustered hospital-associated listeriosis needs to be considered in the differential diagnosis of sepsis in immunocompromised patients, particularly in those treated with new or increased doses of immunosuppressive agents.

An unusual case of acute cystitis associated with mixed flora in voided urine in an adult male.

This report describes two episodes of acute cystitis associated with "mixed flora" in an elderly male following a cystoscopy. The initial episode was accompanied by pyuria and a positive nitrite test. Both episodes responded to treatment with nitrofurantoin. Urine cultures were negative prior to the episodes and at a 1-year follow-up.

Inhibition of the Mycobacterium tuberculosis reserpine-sensitive efflux pump augments intracellular concentrations of ciprofloxacin and enhances susceptibility of some clinical isolates.

BACKGROUND/PURPOSE: Active efflux is known to play a major role in the resistance of many bacteria to antibiotics. To evaluate the possibility of overcoming resistance by suppressing the efflux, we determined the effect of reserpine, an efflux pump inhibitor. METHODS: Intracellular accumulations and the minimal inhibitory concentrations (MICs) of ciprofloxacin in M. tuberculosis H37Rv and 16 clinical isolates were determined, compared, and analyzed. Nine of the clinical isolates were resistant to isoniazid and rifampin (multiple-drug resistant MDR). Five of these were resistant to ciprofloxacin. RESULTS: A reserpine-inhibited efflux system was identified in the H37Rv control and 10:1 (90.9%) of ciprofloxacin-susceptible and 4:1 (80%) of ciprofloxacin-resistant clinical isolates. The MIC of ciprofloxacin decreased in the presence of reserpine in 3/10 (30%) of the ciprofloxacin-susceptible and 2/4 (50%) of the MDR ciprofloxacin-resistant strains that expressed efflux pumps. Two of the efflux-positive, ciprofloxacin-resistant strains in which the MIC of ciprofloxacin was not decreased by reserpine were found to carry a D94A gyrA mutation. In contrast, two strains with the D94G gyrA mutation were susceptible to ciprofloxacin in the presence of reserpine. An efflux-negative strain, highly resistant to multiple antibiotics, was found to have a novel G247S mutation that differs from known mutations in the QRDR region of the gyrA gene. CONCLUSION: These findings indicate t hat reserpine can increase intracellular concentrations of ciprofloxacin, but is unable to overcome other mechanisms of resistance in clinical isolates.

Compliance of health care workers with hand hygiene practices: independent advantages of overt and covert observers.

BACKGROUND: Evaluation and feedback of hand hygiene (HH) compliance are important elements of the WHO multimodal strategy for hospital infection control. Overt observation is recommended, but it may be confounded by Hawthorne effect. Covert observation offers the opportunity to decrease observer bias. In this study we conducted a one year hospital-wide HH promotion program that included medical students (MS) as covert observers. METHODS: HH compliance for the five WHO indications was determined by trained and validated observers. The overt observers consisted of eleven infection control nurses (ICNs) and two unit HH ambassadors (UAs) in each of 83 wards. The covert observers consisted of nine MS during their rotating clinical clerkships. Feedback was provided to department heads and staff each quarter. RESULTS: Of the 23,333 HH observations 76.0% were by MS, 5.3% by ICNs and 18.7% by UAs. The annual compliance rates were MS 44.1%, ICNs 74.4% and UAs 94.1%; P<0.001. The MS found significantly lower annual compliance rates for 4/5 HH indications compared to ICNs and UAs; P<0.05. The ICNs reported significantly improvement from the first to the fourth quarter; P<0.001. This was associated with feedback from the MS of very poor compliance by nurses during the first quarter. CONCLUSIONS: Based on these findings we recommend a two-pronged approach to HH programs. The role of ICNs and UAs is to educate, serve as role models, establish, sustain good HH practices and provide direct feedback. The role of the covert observers is to measure compliance and provide independent feedback.

An indwelling urinary catheter for the 21st century.

What's known on the subject? and What does the study add? A vast literature has been published on the prevalence, morbidity and microbiology of catheter-associated urinary tract infections. Research and development in recent years has focused on producing antibacterial coatings for the indwelling Foley catheter with insufficient attention to its design. This article provides a critical examination of the design of the indwelling Foley catheter. Design specifications are outlined for a urine collection device that should reduce the vulnerability of catheterised urinary tract to infection. The indwelling urinary catheter is the most common cause of infections in hospitals and other healthcare facilities [1]. As long ago as 1958, Paul Beeson [2] warned '… the decision to use this instrument should be made with the knowledge that it involves the risk of producing a serious disease which is often difficult to treat'. Since then, scientific studies have progressed revealing a greater understanding of the bladder's defence mechanisms against infection and how they are undermined by the Foley catheter [3-5]. In addition, the complications caused by the development of bacterial biofilms on catheters have been recognised and the ways in which these bacterial communities develop on catheters have become clear [5,6]. It is now obvious that fundamental problems with the basic design of the catheter, which has changed little since it was introduced into urological practice by Dr Fredricc Foley in 1937 [7], induce susceptibility to infection. These issues need to be addressed urgently if we are to produce a device suitable for use in the 21st century.

Susceptibility of Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and their combination over a 12 year period in Taiwan.

OBJECTIVES: This study was designed to determine the susceptibility of clinical isolates of multidrug-resistant (MDR) and non-MDR Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and trimethoprim/sulfamethoxazole over a 12 year period in Taiwan. PATIENTS AND METHODS: We examined a total of 117 clinical isolates of M. tuberculosis collected from Southern Taiwan, 116 from 1995 to 2006 and an extensively drug-resistant (XDR) isolate in 2009. These included 28 isolates susceptible to all four first-line agents, 52 MDR isolates and 36 isolates with a mixed combination of drug resistance patterns other than MDR and 1 XDR isolate. RESULTS: Sulfamethoxazole inhibited 80% growth of all 117 isolates regardless of their susceptibility to the first-line agents at an MIC(90) of 9.5 mg/L. The concentration required to inhibit 99% growth was 38 mg/L. There were no significant changes in the MIC(50) or MIC(90) of sulfamethoxazole over a 12 year period. All 117 isolates were resistant to trimethoprim at >8 mg/L. The combination of trimethoprim/sulfamethoxazole at a ratio of 1:19 had no additive or synergistic effects. CONCLUSIONS: Sulfamethoxazole inhibited the growth of clinical isolates of M. tuberculosis at achievable concentrations in plasma after oral administration. Susceptibility to sulfamethoxazole remained constant over a 12 year period. Trimethoprim was inactive against M. tuberculosis and trimethoprim/sulfamethoxazole provided no additional activity. Although the current and prior studies demonstrate that sulfamethoxazole is active against M. tuberculosis the search needs to continue for more active, lipid-soluble sulphonamides that are better absorbed into tissues and have improved therapeutic efficacy.

Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis.

The potential mechanisms for altered matrix metalloproteinase (MMP) or tissue inhibitors of matrix metalloproteinase (TIMP) function in patients with syphilis and HIV-1 co-infection (HIV-S) was unclear. To determine the expression of MMP-2, 9 and TIMP-1, 2, 4 in the serum and cerebrospinal fluid (CSF) of HIV-S patients, a total of 20 HIV-S patients and 8 controls were enrolled in a HIV-1 clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of MMP-2, 9, and TIMP-1, 2, 4 were determined by ELISA. Gelatin zymography was used to detect the expression of MMP-2 and MMP-9 in the CSF. Neurosyphilis was defined as a CSF white blood cell count ≥ 20 cells/µL or a reactive CSF Venereal Disease Research Laboratory (VDRL). All the patients with HIV-S were males. Most (85%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≥ 1:32. The median age was 35 years (IQR 30-43). The median CD4 T cell counts at the time of the diagnosis of syphilis were 270 cells/µL (IQR 96-484). Ten patients (50%) had neurosyphilis based on a reactive CSF VDRL test (n=8) or increased CSF white cell counts ≥ 20/µL (n=2). The concentrations of CSF MMP-9, TIMP-1, and TIMP-2 were significantly higher in patients with HIV-S than the controls (P<0.05). The CSF TIMP-4 concentrations were significantly lower in those with HIV-S (452 pg/ml) than controls (3101 pg/ml), P<0001. There were no significant differences in serum concentrations between the groups. The only finding that distinguished HIV-1 patients with from those without neurosyphilis is a significant higher expression of CSF MMP-9. In conclusion, the MMP/TIMP system was found to be dysregulated in patients with HIV-S regardless of whether they met the laboratory definition of neurosyphilis. The CSF level of MMP-9 was the only measure that distinguished those with or without neurosyphilis.

Fish gambler's tenosynovitis caused by Mycobacterium marinum: environmental investigation of a fishing pond in Southern Taiwan.

We describe a patient with Mycobacterium marinum tenosynovitis associated with a fish spine injury acquired at a gambling fishing pond in southern Taiwan and identify the source of the infection. M. marinum was isolated from fishing ponds and underground water and wastewater at the site. The isolates shared the same pulsed-field gel electrophoresis pattern as the patient. M. marinum was not detected in 54 samples obtained from 27 fish. Mycobacterium gordonae was isolated from 24 samples collected from the fish. Mycobacterium abscessus was isolated from 3 fish samples (Lateolabrax japonicus 1 and Sciaenops ocellatus 2). M. abscessus and M. gordonae were isolated from all water samples. This investigation provides strong evidence that the predisposing factor for the M. marinum infection was with a fish spine injury acquired at a gambling fishing pond. The source of the infection was the contaminated pond water.

Urinary-catheter-associated infections in the elderly.

The indwelling urinary catheter is the leading cause of complicated urinary tract infections and Gram-negative bacteraemia in this age group. It accounts for about 40% of life-threatening septicaemia. There is a progressive increase in mortality independently associated with the duration of catheterization. Polymicrobial bacteriuria is common. Urease-producing bacteria lead to encrusted and blocked catheters. The current challenges are to develop effective methods to sensitize healthcare workers to avoid the routine use of indwelling catheters, remove them when no longer needed, develop alternative methods for care of incontinence, employ non-invasive methods to measure urine output, and improve urine drainage systems. The research paradigm needs to focus on prevention of catheter-associated infections rather than on futile attempts to treat irreversible sepsis.

Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995-2003.

OBJECTIVES: Fluoroquinolones are being used more frequently for the treatment of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis complex (MTB). This study was designed to determine the frequency of the emergence of fluoroquinolone-resistant strains in Taiwan and to assess whether this might be due to use of fluoroquinolones for treatment of patients with MDR or because of increased use of fluoroquinolones in the community for treatment of other infections. We also sought to determine whether there might be clonal spread of fluoroquinolone resistance. METHODS: A total of 3497 clinical isolates of M. tuberculosis complex were obtained during 1995-2003, of which 141 were selected. They consisted of 62 isolates fully susceptible to four first-line drugs, 33 isolates resistant to rifampicin and isoniazid (MDR), and 46 isolates with a variety of any drug resistant patterns other than MDR (combination group). The MICs were determined for ciprofloxacin, ofloxacin and levofloxacin. RESULTS: An increase in the MIC90 and rates of resistance to ciprofloxacin, ofloxacin and levofloxacin were noted only in the MDR group. The rates were higher among strains isolated between 1998-2003 compared with those obtained between 1995-1997 (rate of resistance, 20% versus 7.7%; MIC > or = 4 mg/L versus 1-2 mg/L). Among the 10 fluoroquinolone-resistant isolates, five (50%) possessed mutations other than S95T in the gyrA gene. No gyrB mutation was found in any of the clinical isolates. CONCLUSIONS: These findings suggest that fluoroquinolone resistance is the result of treatment of patients with MDR strains rather than from use in the general community in Taiwan. The emergence of fluoroquinolone resistance among MDR strains reinforces the need for routine fluoroquinolone susceptibility testing whenever these drugs might be used.

Who are you--Staphylococcus saprophyticus?

Staphylococcus saprophyticus is a leading cause of cystitis in young women. S. saprophyticus shares many clinical features of urinary tract infection caused by Escherichia coli, but differs in pathogenesis, seasonal variation, and geographic distribution. This review summarizes what is known and what still needs to be learned about this microorganism.