Suzanne E. Geerlings

Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America

Guidelines for the diagnosis, prevention, and management of persons with catheter-associated urinary tract infection (CA-UTI), both symptomatic and asymptomatic, were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic criteria, strategies to reduce the risk of CA-UTIs, strategies that have not been found to reduce the incidence of urinary infections, and management strategies for patients with catheter-associated asymptomatic bacteriuria or symptomatic urinary tract infection. These guidelines are intended for use by physicians in all medical specialties who perform direct patient care, with an emphasis on the care of patients in hospitals and long-term care facilities.

Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV Cohort Study

BACKGROUND Human immunodeficiency virus (HIV)-infected individuals may be at increased risk of age-associated noncommunicable comorbidities (AANCCs). METHODS Cross-sectional analyses of AANCC prevalence (including cardiovascular, metabolic, pulmonary, renal, bone, and malignant disease) and risk factors in a prospective cohort study of HIV type 1-infected individuals and HIV-uninfected controls, who were aged ≥45 years and comparable regarding most lifestyle and demographic factors. RESULTS HIV-infected participants (n = 540) had a significantly higher mean number of AANCCs than controls (n = 524) (1.3 [SD, 1.14] vs 1.0 [SD, 0.95]; P < .001), with significantly more HIV-infected participants having ≥1 AANCC (69.4% vs 61.8%; P = .009). Hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function were significantly more prevalent among HIV-infected participants. Risk of AANCC by ordinal logistic regression was independently associated with age, smoking, positive family history for cardiovascular/metabolic disease, and higher waist-to-hip ratio, but also with HIV infection (odds ratio, 1.58 [95% confidence interval, 1.23-2.03]; P < .001). In those with HIV, longer exposure to CD4 counts <200 cells/µL, and, to a lesser extent, higher levels of high-sensitivity C-reactive protein and soluble CD14, and longer prior use of high-dose ritonavir (≥400 mg/24 hours) were each also associated with a higher risk of AANCCs. CONCLUSIONS All AANCCs were numerically more prevalent, with peripheral arterial, cardiovascular disease, and impaired renal function significantly so, among HIV-infected participants compared with HIV-uninfected controls. Besides recognized cardiovascular risk factors, HIV infection and longer time spent with severe immunodeficiency increased the risk of a higher composite AANCC burden. There was a less pronounced contribution from residual inflammation, immune activation, and prior high-dose ritonavir use.

Antibiotic Prophylaxis in Urologic Procedures: A Systematic Review

OBJECTIVE Antibiotic prophylaxis is used to minimize infectious complications resulting from interventions. Side-effects and development of microbial resistance patterns are risks of the use of antibiotics. Therefore, the use should be well considered and based on high levels of evidence. In this review, all available evidence on the use of antibiotic prophylaxis in urology is gathered, assessed, and presented in order to make choices in the use of antibiotic prophylaxis on the best evidence currently available. METHODS A systematic literature review was conducted, searching Medline, Embase (1980-2006), the Cochrane Library, and reference lists for relevant studies. All selected articles were reviewed independently by two, and, in case of discordance, three, reviewers. RESULTS Only the transurethral resection of prostate (TURP) and prostate biopsy are well studied and have a high and moderate to high level of evidence in favour of using antibiotic prophylaxis. Other urologic interventions are not well studied. The moderate to low evidence suggests no need for antibiotic prophylaxis in cystoscopy, urodynamic investigation, transurethral resection of bladder tumor, and extracorporeal shock-wave lithotripsy, whereas for therapeutic ureterorenoscopy and percutaneous nephrolithotomy, the low evidence favours the use of antibiotic prophylaxis. Urologic open and laparoscopic interventions were classified according to surgical wound classification, since no studies were identified. Antibiotic prophylaxis is not advised in clean surgery, but is advised in clean-contaminated and prosthetic surgery. CONCLUSIONS Except for the TURP and prostate biopsy, there is a lack of well-performed studies investigating the need for antibiotic prophylaxis in urologic interventions.

Future challenges for clinical care of an ageing population infected with HIV: a modelling study

Summary Background The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. Methods We constructed an individual-based model of the ageing HIV-infected population, which followed patients on HIV treatment as they age, develop NCDs—including cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies—and start co-medication for these diseases. The model was parameterised by use of data for 10 278 patients from the national Dutch ATHENA cohort between 1996 and 2010. We made projections up to 2030. Findings Our model suggests that the median age of HIV-infected patients on combination antiretroviral therapy (ART) will increase from 43·9 years in 2010 to 56·6 in 2030, with the proportion of HIV-infected patients aged 50 years or older increasing from 28% in 2010 to 73% in 2030. In 2030, we predict that 84% of HIV-infected patients will have at least one NCD, up from 29% in 2010, with 28% of HIV-infected patients in 2030 having three or more NCDs. 54% of HIV-infected patients will be prescribed co-medications in 2030, compared with 13% in 2010, with 20% taking three or more co-medications. Most of this change will be driven by increasing prevalence of cardiovascular disease and associated drugs. Because of contraindications and drug–drug interactions, in 2030, 40% of patients could have complications with the currently recommended first-line HIV regimens. Interpretation The profile of patients in the Netherlands infected with HIV is changing, with increasing numbers of older patients with multiple morbidities. These changes mean that, in the near future, HIV care will increasingly need to draw on a wide range of medical disciplines, in addition to evidence-based screening and monitoring protocols to ensure continued high-quality care. These findings are based on a large dataset of HIV-infected patients in the Netherlands, but we believe that the overall patterns will be repeated elsewhere in Europe and North America. The implications of such a trend for care of HIV-infected patients in high-burden countries in Africa could present a particular challenge. Funding Medical Research Council, Bill & Melinda Gates Foundation, Rush Foundation, and Netherlands Ministry of Health, Welfare and Sport.

Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus.

Urinary tract infections (UTIs) are more common and tend to have a more complicated course in patients with diabetes mellitus (DM). The mechanisms, which potentially contribute to the increased prevalence of both asymptomatic and symptomatic bacteriuriai in these patients are defects in the local urinary cytokine secretions and an increased adherence of the microorganisms to the uroepithelial cells. The need for treatment of asymptomatic bacteriuria remains controversial. No evidence is available on the optimal treatment of acute cystitis and pyelonephritis in patients with DM. Because of the frequent (asymptomatic) upper tract involvement and the possible serious complications, many experts recommend a 7-14-day oral antimicrobial regimen for bacterial cystitis in these patients, with an antimicrobial agent that achieves high levels both in the urine and in urinary tract tissues. Current data suggest that shorter regimens will lead to failure also in uncomplicated UTI in women. The recommended treatment of acute pyelonephritis does not differ from that in nondiabetic patients. Clinical trials specifically dealing with the treatment of UTIs in diabetic patients, comparing the optimal duration and choice of antimicrobial agent, are needed. Besides that, new approaches to preventive strategies must prove their value in this specific patient group.

Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women

BACKGROUND The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs). METHODS In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. RESULTS After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P = .02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated. CONCLUSION In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094.

Lactobacilli vs Antibiotics to Prevent Urinary Tract Infections: A Randomized, Double-blind, Noninferiority Trial in Postmenopausal Women

BACKGROUND Growing antibiotic resistance warrants studying nonantibiotic prophylaxis for recurrent urinary tract infections (UTIs). Use of lactobacilli appears to be promising. METHODS Between January 2005 and August 2007, we randomized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim-sulfamethoxazole, 480 mg, once daily or oral capsules containing 109 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. Primary end points were the mean number of symptomatic UTIs, proportion of participants with at least 1 UTI during 12 months, time to first UTI, and development of antibiotic resistance by Escherichia coli. RESULTS The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, after 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The between-treatment difference of 0.4 UTIs per year (95% CI, -0.4 to 1.5) was outside our noninferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the trimethoprim-sulfamethoxazole and lactobacilli participants, respectively; median times to the first UTI were 6 and 3 months, respectively. After 1 month of trimethoprim-sulfamethoxazole prophylaxis, resistance to trimethoprim-sulfamethoxazole, trimethoprim, and amoxicillin had increased from approximately 20% to 40% to approximately 80% to 95% in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI. During the 3 months after trimethoprim-sulfamethoxazole discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis. CONCLUSIONS In postmenopausal women with recurrent UTIs, L rhamnosus GR-1 and L reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with trimethoprim-sulfamethoxazole. However, unlike trimethoprim-sulfamethoxazole, lactobacilli do not increase antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094.

First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir.

Objective:We studied changes in bone mineral density (BMD) and bone turnover after initiation of combination antiretroviral therapy (cART) and the contribution of zidovudine/lamivudine (ZDV/3TC) in particular. Design:Randomized clinical trial comparing lopinavir/ritonavir(LPV/r) + ZDV/3TC with LPV/r + nevirapine (NVP) in 50 cART-naive men. Methods:Dual energy X-ray absorptiometry (DXA) and quantitative computed tomography scans (QCT) were performed at baseline and 3, 12, and 24 months after cART initiation. Serum 25-hydroxy-vitamin D3, parathyroid hormone (PTH), osteocalcin, and urine deoxypyridinoline (DPD)/creatinine ratio were measured. Results:BMD decreased rapidly in both femoral neck and lumbar spine after cART initiation. BMD loss during 24 months measured by DXA, but not by QCT, was greater in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group [femoral neck: −6.3% ± 1.0% (P < 0.0001) compared to −2.3% ± 0.9% (P = 0.01), between-group P = 0.0006); lumbar spine: −5.1% ± 0.8% (P < 0.0001) compared to −2.6% ± 0.7% (P = 0.0006), between-group P = 0.07]. Osteocalcin [+1.60 ± 0.32 (P < 0.0001) and +1.81 ± 0.29 (P < 0.0001) nmol/l] and the urine DPD/creatinine ratio [+1.35 ± 0.44 (P = 0.0029) and +1.19 ± 0.38 nmol/mmol (P = 0.0024)] increased in both groups over 24 months, with no significant difference between groups. PTH increased to a greater degree in the NVP/LPV/r group [+2.0 ± 0.31 pmol/l (P < 0.0001)] compared to [+0.81 ± 0.33 pmol/l (P = 0.021) in the ZDV/3TC/LPV/r group]. Conclusion:BMD in both femoral neck and lumbar spine decreased rapidly after initiation of cART, in parallel to an increase in bone turnover. The greater bone loss in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group suggests that ZDV/3TC contributes to this process. The PTH increase does not explain this greater bone loss.

Plasmid-Mediated Resistance in Enterobacteriaceae Changing Landscape and Implications for Therapy

Antimicrobial resistance is increasing worldwide, and pathogenic microorganisms that are resistant to all available antimicrobial agents are increasingly reported. Emerging plasmid-encoded extended-spectrum β-lactamases (ESBLs) and carbapenemases are increasingly reported worldwide. Carbapenemase production encoded by genes located on mobile genetic elements is typically accompanied by genes encoding resistance to other drug classes, often but not necessarily located on the same mobile element. Multiple plasmid-mediated mechanisms of resistance against the fluoroquinolones and aminoglycosides have been described, and the combination of plasmid-mediated resistance with chromosomally encoded resistance mechanisms of multiple drug classes now results in strains that are resistant to all of the main classes of commonly used antimicrobial drugs. Clinical studies of antimicrobial therapy and outcome of patients infected with ESBL- or carbapenemase-producing strains of Enterobacteriaceae compared with patients infected with susceptible strains are limited in their design but suggest a worse outcome after infection with resistant strains.Alternative options for the treatment of infections caused by carbapenem-resistant strains of Enterobacteriaceae are limited. Current strategies include colistin, fosfomycin, tigecycline and temocillin. Although in vitro testing suggests strong activity for each of these drugs against a large proportion of carbapenem-resistant strains of Enterobacteriaceae, clinical evaluations do not provide strong evidence for equivalent or improved outcome. Oral treatment with fosfomycin tromethamine is effective against lower urinary tract infections (UTIs) caused by ESBL-producing Escherichia coli. Intravenous fosfomycin may be beneficial and safe for patients when used as part of a combination therapy in the management of severe infections caused by carbapenem-resistant Klebsiella pneumoniae. Tigecycline is only indicated for the treatment of complicated skin and skin structure infections and complicated intra-abdominal infections in Europe, and is also approved for treatment of community-acquired pneumonia in the US. Clearly, further research on the clinical and safety outcomes in the treatment of multidrug-resistant Enterobacteriaceae with these existing alternative drugs, and the development of new and unrelated drugs, are urgently warranted.

Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss.

Background Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy. Methodology/Principal Findings Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial. Randomisation was between zidovudine-containing therapy (zidovudine/lamivudine+lopinavir/ritonavir) and zidovudine-sparing therapy (nevirapine+lopinavir/ritonavir). Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3, 12, 24 months of antiretroviral therapy. In the zidovudine/lamivudine+lopinavir/ritonavir group, from 3 months onward limb fat decreased progressively by 684±293 grams (estimated mean±standard error of the mean)(p = 0.02) up to 24 months whereas abdominal fat increased, but exclusively in the visceral compartment (+21.9±8.1 cm2, p = 0.008)). In contrast, in the nevirapine+lopinavir/ritonavir group, a generalized increase in fat mass was observed. After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups, but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group (6.1±0.2 versus 5.3±0.2 and 3.6±0.1 versus 2.8±0.1 mmol/l respectively, p<0.05). Virologic response and safety were comparable in both groups. Conclusions/Significance Zidovudine/lamivudine+lopinavir/ritonavir, but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients, is associated with lipoatrophy and greater relative intraabdominal lipohypertrophy, suggesting that zidovudine/lamivudine contributes to both these features of lipodystrophy. These findings support to no longer consider zidovudine/lamivudine as one of the preferred possible components of first-line antiretroviral therapy where alternative treatments are available. Trial Registration ClinicalTrials.gov NCT 00122226