Empirical Use Of Fluoroquinolones Research Articles

Regional variations in antimicrobial susceptibility of community-acquired uropathogenic Escherichia coli in India: Findings of a multicentric study highlighting the importance of local antibiograms

ObjectivesEvidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and Antimicrobial Stewardship (DASH) to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship program guiding centers in preparing, analyzing and disseminating local antibiograms to promote antimicrobial stewardship in community urinary tract infection. Here, we mapped the susceptibility profile of Escherichia coli from 22 Indian centers. MethodsThese centers spanned 10 Indian states and three union territories. Antibiograms for urinary E. coli from the outpatient departments were collated. Standardization was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analyzed. ResultsNationally, fosfomycin, with 94% susceptibility (inter-center range 83-97%), and nitrofurantoin, with 85% susceptibility (61-97%), retained the widest activity. The susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%), and oral cephalosporins (26%). The rates for third- and fourth-generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) extended-spectrum β-lactamase prevalence. Piperacillin-tazobactam (81%), amikacin (88%), and meropenem (88%) retained better activity; however, one center in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West, and Northeast India; centers in the heavily populated Gangetic plains, across north and northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices. ConclusionsFosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated E. coli cystitis in India, although elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third-generation cephalosporins is discouraged, whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents.

Computerized decision support system (CDSS) use for surveillance of antimicrobial resistance in urinary tract infections in primary care.

Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care. To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs. We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections. We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%-42.2%) for amoxicillin, 16.6% (95% CI, 15.9%-17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%-7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%-6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001). CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC.

Impact of inappropriate empirical antibiotic treatment on clinical outcomes of urinary tract infections caused by Escherichia coli: a retrospective cohort study

We aimed to determine the clinical impact of inappropriate empirical antibiotic treatment (IEAT) compared with appropriate empirical antibiotic treatment (AEAT) in hospitalised patients with urinary tract infections (UTIs) caused by Escherichia coli (E. coli). This retrospective cohort study included adult patients with a primary diagnosis of UTI who were treated with empirical antibiotics at a tertiary hospital in southern China over a 2-year period. Clinical data of patients who received IEAT were compared with those of patients receiving AEAT. We used multivariable logistic regression to identify the predictors for receiving IEAT and the risk factors affecting clinical outcomes. A total of 213 patients were enrolled (median age, 61 years), of whom 103 (48.4%) received IEAT. IEAT was associated with empirical use of fluoroquinolones, male sex and age-adjusted Charlson comorbidity index (aCCI) score >6. Hospital length of stay (LOS) was longer for patients who received IEAT than for those who received AEAT (13.6 ± 8.6 days vs. 10.8 ± 7.9 days; P=0.008). IEAT was an independent risk factor for longer LOS along with aCCI score ≥2, lung disease and cardiac disease. Empirical use of fluoroquinolones for UTIs should be avoided, especially in male patients with aCCI score >6. Improved empirical antimicrobial therapy may have a beneficial impact in reducing bacterial resistance and healthcare costs by decreasing the LOS. Therefore, interventions to promote in-depth antibiotic stewardship programmes in China are needed.

Resistance among urinary tract pathogens collected in Europe during 2018

ObjectivesEscherichia coli, Klebsiella pneumoniae and Proteus mirabilis are urinary tract infection (UTI) pathogens and extended spectrum β-lactamase (ESBL)-producing pathogens exhibit co-resistance to oral fluoroquinolones (FQ) and trimethoprim-sulphamethoxazole (TMP-SMX). This study assessed the prevalence of ESBL phenotypes and co-resistance to FQ and TMP-SMX. MethodsIn total, 766 E. coli, 260 K. pneumoniae and 104 P. mirabilis from UTIs in 18 countries were evaluated for susceptibility in the SENTRY surveillance programme, and results interpreted using EUCAST criteria. ResultsE. coli, K. pneumoniae and P. mirabilis accounted for 57.1%, 11.3% and 7.8%, respectively, of the isolates. Among E. coli, resistance to levofloxacin and TMP-SMX ranged from 21.8% to 32.7% for all isolates increasing to 66.5–67.0% among those with a ESBL phenotype (17.9% of all UTI E. coli from Europe were ESBL phenotypes). In contrast, all E. coli were susceptible to meropenem. For K. pneumoniae, resistance rates for levofloxacin and TMP-SMX were 32.2–40.0% increasing to 69.1–78.6% for ESBL phenotypes. Meropenem was the most active agent, with 7.7% resistance. Among P. mirabilis resistance to levofloxacin and TMP-SMX was 26–38.5% and increased to 100% for ESBL phenotypes. No meropenem-resistant P. mirabilis were reported. ConclusionsHigh co-resistance rates were observed for oral antibiotics among ESBL phenotypes raising concerns regarding empiric use of FQ and TMP-SMX for treating resistant UTIs outside of the hospital. In contrast, intravenous carbapenems retain activity against resistant UTI pathogens. New oral options with the spectrum of the carbapenems would address an unmet need for managing resistant UTIs.

Частота выявляемости и резистентность основных нозокомиальных уропатогенов в моче урологических больных в Ивановском регионе

To clarify the etiology of nosocomial UTIs occurring in the urology departments and the outpatient clinic of the Ivanovo Regional Clinical Hospital (IvRCH), to develop recommendations on the empirical use of antibiotic therapy. Bacterial composition of urine in urological patients was monitored from 1999 to 2015. The sensitivity of the pathogens to the main antibacterial agents was determined using the Kirby-Bauer disk diffusion susceptibility test. The study determined the frequency of detecting pathogens associated with urinary tract infections in adults and children, established the association between the spectrum of pathogens and patient age and determined the most effective antibacterial drugs in patients with nosocomial UTI in the Ivanovo region. High resistance levels of E. coli strains were detected against fluoroquinolones, nalidixic acid, and nitrofurans; they were three times higher than that against cephalosporins. The findings show the need to reduce the empirical use of fluoroquinolones, nalidixic acid, and nitrofurans and completely exclude the use of ampicillin in patients with nosocomial UTI in the Ivanovo region. To reduce the occurrence of nosocomial infections, patients discharged from the hospital should be administered empirical therapy with third-generation cephalosporins.

Antimicrobial Prescribing in Dogs and Cats in Australia: Results of the Australasian Infectious Disease Advisory Panel Survey.

BackgroundInvestigations of antimicrobial use in companion animals are limited. With the growing recognition of the need for improved antimicrobial stewardship, there is urgent need for more detailed understanding of the patterns of antimicrobial use in this sector.ObjectivesTo investigate antimicrobial use for medical and surgical conditions in dogs and cats by Australian veterinarians.MethodsA cross‐sectional study was performed over 4 months in 2011. Respondents were asked about their choices of antimicrobials for empirical therapy of diseases in dogs and cats, duration of therapy, and selection based on culture and susceptibility testing, for common conditions framed as case scenarios: 11 medical, 2 surgical, and 8 dermatological.ResultsA total of 892 of the 1,029 members of the Australian veterinary profession that completed the survey satisfied the selection criteria. Empirical antimicrobial therapy was more common for acute conditions (76%) than chronic conditions (24%). Overall, the most common antimicrobial classes were potentiated aminopenicillins (36%), fluoroquinolones (15%), first‐ and second‐generation cephalosporins (14%), and tetracyclines (11%). Third‐generation cephalosporins were more frequently used in cats (16%) compared to dogs (2%). Agreement with Australasian Infectious Disease Advisory Panel (AIDAP) guidelines (generated subsequently) was variable ranging from 0 to 69% between conditions.Conclusions and Clinical ImportanceChoice of antimicrobials by Australian veterinary practitioners was generally appropriate, with relatively low use of drugs of high importance, except for the empirical use of fluoroquinolones in dogs, particularly for otitis externa and 3rd‐generation cephalosporins in cats. Future surveys will determine whether introduction of the 2013 AIDAP therapeutic guidelines has influenced prescribing habits.

Pneumococcal Bacteremia in Patients With Cancer

Background One of the major causes of morbidity and mortality in patients with cancer is infection. Gram-positive bacteremias now represent 40% to 50% of all bacteremic episodes in neutropenic patients with cancer. However, pneumococcal bacteremia is uncommon in patients with cancer including those who are neutropenic. Resistance to commonly used antibiotics is expected in our population because of heavy exposure to prophylactic and empiric use of fluoroquinolones and β-lactams. Materials and Methods We reviewed the records of patients with documented Streptococcus pneumoniae bacteremia at the Moffitt Cancer Center between June 2003 and January 2013. The study population was identified by positive blood cultures obtained from the microbiology laboratory during the same period of time. Results During the study period, 27 episodes of Streptococcus pneumoniae bacteremia occurred and were analyzed. Of the 27 patients, 13 (48%) were males with a mean age of 55 years (range, 22–78 years). Most of the patients (78%) received empirical antibiotic treatment as soon as bacteremia was clinically suspected on the basis of fever. Ten (37%) cases were resistant to ceftriaxone, 11 (41%) were resistant to penicillin, and 13 (48%) were resistant to levofloxacin. Seven (26%) patients were neutropenic (absolute neutrophil count, <1500/uL) at the onset of the bacteremia. Thirteen (50%) had hematologic malignancies and 13 (50%) had a solid tumor. Four (15%) patients had chronic obstructive pulmonary disease, 3 (11%) had asthma, and 1 (4%) had pulmonary fibrosis. One patient did not receive any empirical treatment, deteriorated, and died within 24 hours after onset of the initial symptoms. Overall, 3 (11%) patients died during their hospital stay. Conclusions Pneumococcal bacteremia is found in patients with humoral immune defects such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, and those with underlying lung disease. Although pneumococcal bacteremia remains rare in patients with cancer including those with neutropenia, resistance to commonly used antibiotics is higher than expected. Our study illustrates the difficulty of choosing empiric antibiotics for patients with suspected pneumococcal bacteremia with such a high level of resistance.

Résistance aux fluoroquinolones en 2013 : quel impact pour l’interniste ?

Because of their important qualities, fluoroquinolones are amongst the most prescribed antibiotics in the world. The corollary of this success is the rapid increase in resistance to fluoroquinolones, responsible for treatment failures. Moreover, fluoroquinolone-resistance is often accompanied by resistance to other classes of antibiotics. Currently, significant levels of resistance are found both in hospitals and in community settings, severely limiting possibilities for empirical use of fluoroquinolones. A major mechanism explaining the rapid emergence of resistance to fluoroquinolones is their specific impact on human microbiota and the selection of resistant strains in the microbiota, which seems to be an unavoidable ecological side effect. In order to preserve the efficiency of this important class of antibiotics, limiting their use and respecting good practice recommendations are essential.

A comparative study of profile of infections in diabetic and non-diabetic Patients

Background: Diabetes mellitus is a chronic disorder and its association with an increased propensity of infection has in general, been well recognized. Clinical data on the association of diabetes mellitus with common infections are virtually lacking, not conclusive and often biased. Aims & Objective: The present study was done to determine profile of various infections with their etiological agents and antibiotic sensitivity pattern among diabetic and non-diabetic patients. Materials and Methods: A Cross-sectional descriptive study was conducted at a tertiary care hospital in India. The study included 100 diabetic and 100 non-diabetic patients with suspected infections and samples were processed for culture and antibiotic sensitivity testing. The analysis was done using the software Statistical Package for Social Scientists (SPSS) 15.0. Results: Infections encountered in diabetics were urinary tract infection (UTI) (32%), skin and soft tissue infection (12%), lower respiratory tract infection (LRTI) (8%), septicemia (3%) and ascites (1%) whereas prevalence of various infections in non-diabetic patients were UTI (13%), skin and soft tissue infection (19%), LRTI (10%), septicemia (2%), acute appendicitis (1%) and enteric fever (1%). Among various infections, prevalence of urinary tract infection was significantly higher in diabetics (32%) than non-diabetics (13%) (P value = 0.001). Resistance to fluoroquinolones among urinary isolates of E.coli was significantly higher (89.5%) in diabetic patients compared to (50%) in non-diabetic patients (P value = 0.02). Conclusion: Prevalence of UTI was significantly higher in diabetics than non-diabetics where E.coli was the predominant pathogen in both the group of patients. Fluoroquinolones resistance was more common in diabetic than non – diabetics. We would like to recommend restriction of empirical use of fluoroquinolones in diabetic patients. Carbapenem, Amikacin, Piperacillin-tazobactum and Nitrofurantoin still has acceptable sensitivity against uropathogenic E. coli in both the group of patients and can still be used in treatment failure.

Empirical use of fluoroquinolones for chest infections may mask tuberculosis and jeopardise chances of survival [Editorial

Empirical use of fluoroquinolones for chest infections may mask tuberculosis and jeopardise chances of survival [Editorial

Empirical use of fluoroquinolones improves the survival of critically ill patients with tuberculosis mimicking severe pneumonia

IntroductionEmpirical use of fluoroquinolones may delay the initiation of appropriate therapy for tuberculosis (TB). This study aimed to evaluate the impact of empirical fluoroquinolone use on the survival of patients with pulmonary TB that mimicked severe community-acquired pneumonia (CAP) requiring intensive care.MethodsPatients aged >18 years with culture-confirmed pulmonary TB who presented as severe CAP and were admitted to the ICU were divided into fluoroquinolone (FQ) and nonfluoroquinolone (non-FQ) groups based on the type of empirical antibiotics used. Those patients with previous anti-TB treatment or those who died within 3 days of hospitalization were excluded. The primary end point was 100-day survival.ResultsOf the 77 patients identified, 43 (56%) were in the FQ group and 34 (44%) were in the non-FQ group. The two groups had no statistically significant difference in co-morbidities (95% vs. 97%, P > 0.99) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores (21.2 ± 7.1 vs. 22.5 ± 7.5, P = 0.46) on ICU admission. Overall, 91% and 82% of patients in the FQ and non-FQ groups, respectively, had sputum examinations for TB within 1 week of admission (P = 0.46), and results were positive in 7% and 15% (P = 0.47), respectively. For both groups, 29% received appropriate anti-TB therapy within 2 weeks after ICU admission. The 100-day mortality rate was 40% and 68% for the FQ and non-FQ groups, respectively (P = 0.02). By Cox regression analysis, APACHE score <20, no bacteremia during the ICU stay, and empirical fluoroquinolone use were independently associated with survival.ConclusionEmpirical use of fluoroquinolones may improve the survival of ICU patients admitted for pulmonary TB mimicking severe CAP.

Population-based investigation of fluoroquinolones resistant tuberculosis in rural eastern China

Empirical use of fluoroquinolones (FQ) to treat a variety of bacterial infections may inadvertently select for FQ-resistant strains of Mycobacterium tuberculosis(MTB), especially in rural China where the use of FQ in treating infections has not been standardized. Here we determine the prevalence and describe the transmission of FQ-resistant MTB in two rural counties in eastern China through a combination of conventional epidemiology with IS6110-based restriction fragment length polymorphism(RFLP) analysis and DNA sequencing of drug-resistance determining regions. Phenotypic FQ resistance was detected in 31 of 351(8.8%) isolates. FQ resistance was equally distributed between patient-isolates deemed drug resistant and drug-susceptible, but mostly observed in those with treatment history of respiratory infection. Mutations in gyrA were found in 54.8% of FQ resistant isolates, and one isolate with a gyrB mutation. Despite predominating in entire bacilli population(69.2%), Beijing family strain had similar proportion of FQ resistance to the other(10.3% vs. 4.7%, p = 0.060). IS6110RFLP identified 2 clusters(4 isolates) among FQ resistant isolates and 3 clusters composed of both 4 FQ resistant isolates and 6 FQ susceptible isolates. Our results indicate that FQ-resistant MTB has emerged among the circulating bacillary population in rural eastern China. The relatively low level of clustering among FQ-resistant strains suggests most are acquired de novo, likely due to widespread FQ use.

Trends in antibiotic susceptibility of bloodstream pathogens in hospitalized patients in France, 1996 to 2007

Nationwide surveys of antimicrobial susceptibility of bacteria isolated from bloodstream infections are required to fit empiric therapy to recent trends and detect emerging resistance. We report the results of a French national prospective survey based on the College of Bacteriology–Virology and Hygiene study group network performed each October during the 1996 to 2007 period, with focus on Enterobacteriaceae (7708 isolates) and Staphylococcus aureus (2271 isolates). The most relevant antimicrobial susceptibilities trends were i) a decrease in fluoroquinolones susceptibility among Enterobacteriaceae (96–90%, P < 0.0001) and Escherichia coli isolates (98–89%, P < 0.0001), respectively, ii) the slight but significant decrease in cefotaxime susceptibility among E. coli ( P = 0.016), and iii) the significant increase in gentamicin susceptibility among S. aureus strains ( P = 0.016). This survey reports antibiotic susceptibility of bloodstream pathogens in France. The empiric use of fluoroquinolones in severe infections should be cautiously monitored by thorough clinical and microbiologic follow-up.

Fluoroquinolone-Resistant Pseudomonas aeruginosa in Chronic Rhinosinusitis

Background:Pseudomonas aeruginosa is cultured in nearly 1 of 5 patients with chronic rhinosinusitis and a history of sinus surgery. Fluoroquinolones are the only enterally administered antibiotics with efficacy against P. aeruginosa, but their frequent empiric use in the community raises concern for a rise in resistance. Objective: It was the aim of this study to determine the prevalence of fluoroquinolone-resistant P. aeruginosa in a tertiary rhinology practice. Methods: All bacterial sinus culture results from the outpatient otolaryngology clinic that yielded P. aeruginosa over a 5-year period (2002–2007) were reviewed along with the medical records of a randomly selected subset of patients. Results: In total, 689 culture results of 324 patients were examined. Nearly all patients had a history of endoscopic sinus surgery. Of all P. aeruginosa cultured, 13% were resistant to levofloxacin and 5% were intermediately sensitive, while 5% were resistant to ciprofloxacin and 7% intermediately sensitive. Of the 324 patients in the study, 19 and 15% had a history of a P. aeruginosa culture resistant to levofloxacin or ciprofloxacin, respectively. Mucoid strains of P. aeruginosa were significantly more likely to be fluoroquinolone resistant. No patient comorbidities were associated with a higher rate of resistance. The prevalence of resistant cultures remained stable over the 5-year study period. Conclusions:P. aeruginosa is cultured primarily in patients with previous sinus surgery. Nearly 20% of isolates are resistant to fluoroquinolones. Resistance to levofloxacin is more common than resistance to ciprofloxacin. This study supports the use of culture-directed therapy in the management of the postfunctional endoscopic sinus surgery patient and the avoidance of empiric use of fluoroquinolones.

Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study

BackgroundThe aims of this study were to determine the antimicrobial susceptibility patterns of urinary isolates from community acquired acute uncomplicated urinary tract infections (uUTI) and to evaluate which antibiotics were empirically prescribed in the outpatient management of uUTI.MethodsAmong the patients which were admitted to outpatient clinics of Ankara University Medical Faculty, Ibni-Sina Hospital during 2005-2006, a total of 429 women between the age of 18 and 65 years old who were clinically diagnosed with uUTI and to whom prescribed empirical antibiotics were enrolled in this prospective observational study. Patients' demographical data, urine culture results, resistance rates to antimicrobial agents and prescribed empiric antimicrobial therapy were analyzed.ResultsTotally 390 (90.9%) patients among all study population were requested for urine culture by their physicians. 150 (38.5%) of these urine cultures were positive. The most common isolated uropathogen was Escherichia coli (E. coli) (71.3%). The variations of uropathogens according to age and menopause status were not significantly different.The resistance rates of E. coli isolates for ampicillin, ampicillin-sulbactam, amoxicillin-clavulonate, cefuroxime, ceftriaxone, fluoroquinolones (FQ), co-trimoxazole (TMP-SMX) and gentamicin were 55.1%, 32.7%, 32.7%, 23.4%, 15.9%, 25.2%, 41.1%, 6.1% respectively. FQ were the most common prescribed antibiotics (77.9%) (P < 0.001), followed by TMP-SMX (10.7%), fosfomycin (9.2%), nitrofurantoin (2.1%). Treatment durations were statistically longer than the recommended 3-day course (P < 0.001).ConclusionEmpirical use of FQ in uUTI should be discouraged because of increased antimicrobial resistance rates.

Reducing empirical use of fluoroquinolones for Pseudomonas aeruginosa infections improves outcome

We previously reported ciprofloxacin resistance (CR) and empirical use of fluoroquinolones as predictors of mortality in patients infected with Pseudomonas aeruginosa in a case-control study. Here, we assessed the clinical impact of reducing empirical fluoroquinolone use for P. aeruginosa infections in hospitalized patients by performing a follow-up study in 2005-06 [period 2 (P2)] and comparing this with prior data from 2001-02 [period 1 (P1)]. Medical charts of infected patients who received at least 72 h of antibiotic therapy were reviewed. Patients were subgrouped based on the susceptibility of infected strains into the CR or ciprofloxacin-susceptible group. Antibiograms, patient and treatment variables and outcome measures were compared between groups and between study periods. Study patients were elderly (median age, 76 years), had a median of three co-morbidities and a median APACHE II score of 13. Most (75%) had pneumonia or urosepsis. Empirical use of fluoroquinolones was reduced by 30% in P2 versus P1, with a corresponding 39% increase in piperacillin/tazobactam use. The resultant positive impact observed in the CR group during P2 includes shortened delay to receipt of effective therapy (1 versus 3.5 days, P < 0.0001), reduced length of stay (13 versus 16 days, P = 0.03) and 2-fold lower mortality (9% versus 22%, P = 0.05). Susceptibility of P. aeruginosa improved by 10% to all antipseudomonal agents tested. In settings where high rates of fluoroquinolone resistance exist, use of non-fluoroquinolone-based empirical regimens for P. aeruginosa infections improves patient outcomes and organism susceptibility over time.

Impact of an antibiotic restriction policy on the antibiotic resistance patterns of Gram-negative microorganisms in an Intensive Care Unit in Greece

The purpose of this study was to investigate the influence of an antibiotic policy programme based on restriction of the empirical use of fluoroquinolones and ceftazidime on the susceptibilities of Gram-negative microorganisms in a general Intensive Care Unit (ICU). The epidemiology of infections caused by the predominant ICU pathogens, i.e. Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, and their resistance patterns as well as antibiotic consumption were recorded for a 6-month period. An antibiotic restriction policy including ceftazidime and quinolones was applied. After an 18-month period of protocol application, the same parameters were recorded for another 6-month period. Consumption of restricted and overall antibiotics was reduced by 92.5% and 55.4%, respectively. Susceptibilities to ciprofloxacin of the three predominant infection-causing Gram-negative bacilli were significantly increased. Ceftazidime showed an increase in susceptibility only for P. aeruginosa. Similar rates of infectious episodes were recorded in the two periods and no differences were observed either in overall mortality or in ICU ecology as expressed by the type of microorganisms implicated in colonisation and/or infection. The reported data suggest that an antibiotic restriction policy can significantly reduce antimicrobial consumption and antimicrobial resistance rates, although the latter effect can be also influenced by the prevalent resistance mechanisms and the prevalence of imported resistance.

Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition and impact on outcomes

Resistance among Pseudomonas aeruginosa has risen dramatically and parallels the increase in fluoroquinolone (FQ) prescribing in recent years. Risk factors for FQ resistance in P. aeruginosa and its impact on outcomes need to be well characterized. A case-control study was carried out on hospitalized adult patients from whom FQ-resistant (case) and FQ-susceptible (control) P. aeruginosa were isolated. A total of 177 patients with positive cultures (91 cases and 86 controls) and 119 with documented infections (65 cases, 54 controls) were included in risk factor and outcomes analysis, respectively. Independent risk factors for FQ resistance were: FQ exposure (OR 12.6, CI 4.95-32), nosocomial acquisition (OR 8.6, CI 3.5-20.7), and diabetes mellitus (OR 6.4, CI 2.1-19.3). An FQ agent was prescribed in 59% of patients receiving an 'antipseudomonal' empirical regimen. Compared with controls, FQ-resistant cases had a median delay to receiving effective therapy of 3.5 days versus 1 day and poorer outcomes: (i) lower complete response rate (45% versus 63%, P=0.04); (ii) longer time to achieve clinical stability (8 days versus 3 days, P=0.005); and (iii) higher infection-related mortality (21% versus 7%; OR = 2.9, 0.9-9.4). Empirical FQ use (OR 4.6, CI 1.5-14.3), FQ resistance (OR 3.6, CI 1.0-13.1), and high APACHE II score (OR 1.1, CI 1.0-1.2) were independent risk factors for increased mortality. FQ exposure from widespread prescribing is a modifiable risk factor for FQ resistance in P. aeruginosa. FQ empirical therapy for Pseudomonas infections may be associated with significant delays in administering effective therapy resulting in adverse outcomes.

Empirical Therapy for Uncomplicated Urinary Tract Infections in an Era of Increasing Antimicrobial Resistance: A Decision and Cost Analysis

Infectious Diseases Society of America guidelines state that uncomplicated urinary tract infections (UTIs) should be treated empirically with trimethoprim-sulfamethoxazole (TMP-SMZ), unless the community resistance among uropathogens exceeds 10%-20%, in which case a fluoroquinolone (FQ) should be used. However, the data to support this threshold are limited. We performed a cost-minimization and sensitivity analysis to determine what level of TMP-SMZ resistance in a community should trigger FQ use. The mean cost of empirical treatment with TMP-SMZ was US$92 when the proportion of resistant Escherichia coli was 0%, $106 when it was 20%, and $120 when it was 40%. The mean cost of empirical FQ treatment was $107 at current levels of FQ resistance. When >22% of E. coli in a community are TMP-SMZ-resistant, empirical FQ therapy becomes less costly than TMP-SMZ therapy. Treatment guidelines for empirical treatment of UTIs may need modification, and the threshold trigger for empirical FQ use should be raised to >20% TMP-SMZ resistance.