Ceftolozane/tazobactam for the treatment of XDR Pseudomonas aeruginosa infections.

PURPOSE: The aim of this study was to evaluate the effectiveness of ceftolozane/tazobactam (C/T) for treating extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) infections, and to analyze whether high C/T dosing (2 g ceftolozane and 1 g tazobactam every 8 h) and infection source control have an impact on outcome. METHODS: Retrospective study of all consecutive patients treated with C/T for XDR-PA infection at a tertiary referral hospital (November 2015-July 2017). Main clinical and microbiological variables were analyzed. RESULTS: Thirty-eight patients were included. Median age was 59.5 years and Charlson Comorbidity Index was 3.5. Fourteen (36.8%) patients had respiratory tract infection, six (15.8%) soft tissue, and six (15.8%) urinary tract infection. Twenty-three (60.5%) received high-dose C/T and in 24 (63.2%) C/T was combined with other antibiotics. At completion of treatment, 33 (86.8%) patients showed clinical response. At 90 days of follow-up, 26 (68.4%) achieved clinical cure, and 12 (31.6%) had clinical failure because of persistent infection in one patient, death attributable to the XDR-PA infection in four, and clinical recurrence in seven. All-cause mortality was 5 (13.2%). Lower C/T MIC and adequate infection source control were the only variables significantly associated with clinical cure. CONCLUSIONS: C/T should be considered for treating XDR-PA infections, with infection source control being an important factor to avoid failure and resistance.

A Cohort Study of Risk Factors That Influence Empirical Treatment of Patients with Acute Pyelonephritis.

The aim of the current study was to compare community-acquired acute pyelonephritis (CA-APN) with health care-associated acute pyelonephritis (HCA-APN), describe the outcomes, and identify variables that could predict antimicrobial susceptibility. We conducted an observational study that included all consecutive episodes of acute pyelonephritis (APN) in adults during 2014 at a Spanish university hospital. From each episode, demographic data, comorbidities, clinical presentation, microbiological data, antimicrobial therapy, and outcome were recorded. A multivariable logistic regression model was performed to define the variables associated with antimicrobial resistance. A total of 607 patients, 503 (82.9%) with CA-APN and 104 (17.1%) with HCA-APN, were included in the study. Patients with HCA-APN were older than patients with CA-APN (70.4 versus 50.6 years; P < 0.001) and had higher rates of previous urinary tract infections (UTIs) (56.5% versus 24.5%; P < 0.001) and previous antibiotic use (56.8% versus 22.8%; P < 0.001). Escherichia coli was more frequently isolated from patients with CA-APN than from patients with HCA-APN (79.9% versus 50.5%; P < 0.001). The rates of resistance of Escherichia coli strains from CA-APN patients versus HCA-APN patients were as follows: amoxicillin-clavulanic acid, 22.4% versus 53.2% (P = 0.001); cefuroxime, 7.7% versus 43.5% (P = 0.001); cefotaxime, 4.3% versus 32.6% (P < 0.001); ciprofloxacin, 22.8% versus 74.5% (P < 0.001); and co-trimoxazole, 34.5% versus 58.7% (P = 0.003). The site of acquisition, recurrent UTIs, and previous antibiotic use were independent risk factors for antimicrobial resistance. Relapse rates were significantly higher when definitive antimicrobial treatment was not adequate (37.1% versus 9.3% when definitive antimicrobial treatment was adequate; P < 0.001). Our study reflects the rise of resistance to commonly used antibiotics in acute pyelonephritis. In order to choose the adequate empirical antibiotic therapy, risk factors for resistance should be considered.

Potential Use of Fosfomycin-Tromethamine for Treatment of Recurrent Campylobacter Species Enteritis.

We report 2 cases of recurrent Campylobacter coli enteritis caused by macrolide- and fluoroquinolone-resistant strains in 2 patients with hypogammaglobulinemia, successfully treated with a prolonged course of fosfomycin-tromethamine with no side effects. Fosfomycin-tromethamine may be a feasible alternative therapy for recurrent enteritis caused by Campylobacter species resistant to first-line drugs.

Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis.

This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis.

High doses of daptomycin (10 mg/kg/d) plus rifampin for the treatment of staphylococcal prosthetic joint infection managed with implant retention: a comparative study.

We aimed to analyze the efficacy and safety of high doses of daptomycin (10 mg/kg/d) plus rifampin (D10 + R) for prosthetic joint infection (PJI). This was an observational retrospective multicenter study (2010-2012) including all patients with acute PJI by fluoroquinolone-resistant staphylococci managed with implant retention and D10 + R. Twenty cases were included: 2 (10%) were withdrawn due to toxicity, leaving 18 cases for efficacy evaluation: 13 (72%) women, age 79 years (range 58-90). Clinical failure was observed in 9 (50%) patients: in 5 cases, staphylococci were recovered (28% of microbiological failures); no modification of daptomycin-MIC was observed. These 18 cases were compared with 44 matched historical cases: failure rate was similar, but whereas in the historical series, failure occurred fundamentally during therapy, in the present series, it was recorded after discontinuation of antibiotics. In summary, D10 + R may be the initial treatment of choice for PJI by fluoroquinolone-resistant staphylococci managed with implant retention.

Etiología y sensibilidad de los uropatógenos identificados en infecciones urinarias bajas no complicadas de la mujer (Estudio ARESC): implicaciones en la terapia empírica / Etiology and sensitivity of uropathogens identified in uncomplicated lower urinary tract infections in women (ARESC Study): implications on empiric therapy

Pacientes y método: Estudio multicéntrico ARESC de 9 hospitales españoles, que incluyó de forma consecutiva 803 mujeres, de edades entre 18 y 65 años, con cistitis no complicada, con el fin de identificar la etiología y evaluar su sensibilidad a 9 antimicrobianos. Resultados: De 803 pacientes consecutivas con ITU baja no complicada, fueron finalmente incluidas 784 pacientes. El urocultivo fue positivo en el 87,7% de las muestras. De un total de 650 uropatógenos, Escherichia coli (E. coli) fue el más frecuente (79,2%), seguido por Staphylococcus saprophyticus (4,4%), Proteus mirabilis (4,3%), Enterococcus faecalis (3,2%) y Klebsiella pneumoniae (2,3%). E. coli mostró una elevada sensibilidad a fosfomicina (97,2%), nitrofurantoína (94,1%) y algo menor a ciprofloxacino (88,1%). Las tasas de resistencia a fluorquinolonas fueron más elevadas en mujeres postmenopáusicas (17 frente a 10%). E. coli sigue presentando unas elevadas resistencias a ampicilina (65%) y a cotrimoxazol (34%), y en la actualidad, aproximadamente un 25% de las cepas son resistentes a amoxicilina/clavulánico y cefuroxima. Conclusiones: En España se observan elevados índices de resistencia de E. coli a antibióticos de amplio uso. Fosfomicina y nitrofurantoína preservan una elevada actividad in vitro. Considerando otros aspectos prácticos, como la posología (una sola dosis) y la influencia del consumo total de quinolonas sobre los niveles de resistencia en enterobacterias y en otros microorganismos, fosfomicina trometamol representa una alternativa empírica de primera elección para la cistitis no complicada de la mujer (AU)

Background and objective: To determine the etiology and susceptibility of uropathogens identified in women with uncomplicated lower urinary tract infections (UTI). Patients and methods: In a multicenter study (ARESC) in 9 Spanish hospitals, 803 female patients with uncomplicated cystitis were consecutively enrolled and evaluated to identify the uropathogens and their susceptibility to 9 antimicrobials.Results: Of 803 patients with uncomplicated cystitis, 784 patients were included. A positive urine culture was found in 87.7% of the samples. Of the 650 pathogens isolated, Escherichia coli (E. coli) was the most frequent (79.2%) followed by Staphylococcus saprophyticus (4.4%), Proteus mirabilis (4.3%), Enterococcus faecalis (3.2%) and Klebsiella pneumoniae (2.3%). E. coli showed a high rate of susceptibility to phosphomycin (97.2%), nitrofurantoin (94.1%) and somewhat lower to ciprofloxacin (88.1%). Fluorquinolone resistance rates were higher among postmenopausal women (17 versus 10%). E. coli was highly resistant to ampicillin (65%) and cotrimoxazole (34%) and 25% of the strains were resistant to amoxicillin/clavulanalic acid and cefuroxime. Conclusions: In Spain, E. coli shows high resistance rates to widely used antimicrobial antibiotics. Phosphomycin and nitrofurantoin have a high in vitro activity. Taking into account practical aspects such as convenience (only one dose), and the influence of the amount of fluorquinolone use on enterobacteriaceae and other microorganisms resistance levels, phosphomycin trometamol represents the option of first choice for the empirical treatment of uncomplicated cystitis in women (AU)

[Etiology and sensitivity of uropathogens identified in uncomplicated lower urinary tract infections in women (ARESC Study): implications on empiric therapy]. / Etiología y sensibilidad de los uropatógenos identificados en infecciones urinarias bajas no complicadas de la mujer (Estudio ARESC): implicaciones en la terapia empírica.

BACKGROUND AND OBJECTIVE: To determine the etiology and susceptibility of uropathogens identified in women with uncomplicated lower urinary tract infections (UTI). PATIENTS AND METHODS: In a multicenter study (ARESC) in 9 Spanish hospitals, 803 female patients with uncomplicated cystitis were consecutively enrolled and evaluated to identify the uropathogens and their susceptibility to 9 antimicrobials. RESULTS: Of 803 patients with uncomplicated cystitis, 784 patients were included. A positive urine culture was found in 87.7% of the samples. Of the 650 pathogens isolated, Escherichia coli (E. coli) was the most frequent (79.2%) followed by Staphylococcus saprophyticus (4.4%), Proteus mirabilis (4.3%), Enterococcus faecalis (3.2%) and Klebsiella pneumoniae (2.3%). E. coli showed a high rate of susceptibility to phosphomycin (97.2%), nitrofurantoin (94.1%) and somewhat lower to ciprofloxacin (88.1%). Fluorquinolone resistance rates were higher among postmenopausal women (17 versus 10%). E. coli was highly resistant to ampicillin (65%) and cotrimoxazole (34%) and 25% of the strains were resistant to amoxicillin/clavulanalic acid and cefuroxime. CONCLUSIONS: In Spain, E. coli shows high resistance rates to widely used antimicrobial antibiotics. Phosphomycin and nitrofurantoin have a high in vitro activity. Taking into account practical aspects such as convenience (only one dose), and the influence of the amount of fluorquinolone use on enterobacteriaceae and other microorganisms resistance levels, phosphomycin trometamol represents the option of first choice for the empirical treatment of uncomplicated cystitis in women.

Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia: results of an open, non-comparative study.

BACKGROUND: Infection is one of the main problems associated with long-term central venous catheters. This study assesses the effectiveness of antibiotic-lock therapy (ALT) for treating catheter-related bacteraemia (CRB). METHODS: CRB was defined as quantitative blood culture counts through any catheter lumen 5-fold greater than concurrent peripheral blood culture, and qualitative blood culture positive for the same microorganism in all samples. Systemic treatment and ALT were started simultaneously using vancomycin (2000 mg/L) for Gram-positive organisms, and ciprofloxacin or amikacin (2000 mg/L) for Gram-negative bacilli. Heparin was added to ALT. Effectiveness was assessed by clinical and microbiological criteria. Cure was defined as negative blood cultures at both sites without catheter removal at 1 month after the completion of therapy. RESULTS: A total of 115 episodes of CRB in 98 patients were analysed. Catheters were used for chemotherapy (50 episodes), haemodialysis (37), total parenteral nutrition (24) and combined chemotherapy and nutrition (4). Median time from catheter placement to CRB onset was 105 days (IQ range 26-210). Aetiologies included Gram-positive organisms [56 coagulase-negative staphylococci (CoNS), 20 Staphylococcus aureus and 5 other organisms] in 81 episodes (70%), Gram-negative bacilli (11 Escherichia coli, 5 Pseudomonas aeruginosa and 10 other organisms) in 26 (23%) and polymicrobial in 8 (7%). A total of 94 episodes were cured (82%). There were 21 therapeutic failures: 9 S. aureus (1 related death), 9 CoNS, 1 P. aeruginosa, 1 Proteus vulgaris and 1 polymicrobial. Median catheter follow-up in therapeutic success was 168 days (range 7-2740). CONCLUSIONS: ALT combined with systemic antibiotics seems to be effective for treating CRB, especially in Gram-negative and CoNS episodes. S. aureus CRB had an elevated rate of therapeutic failure.

Influence of penicillin resistance on outcome in adult patients with invasive pneumococcal pneumonia: is penicillin useful against intermediately resistant strains?

OBJECTIVES: To compare outcome between patients with pneumonia due to penicillin-susceptible S. pneumoniae and patients with pneumonia due to penicillin intermediately resistant strains and to study the outcome of patients with pneumococcal pneumonia caused by strains with MICs of 0.12-1 mg/L treated empirically during the first 48 h with beta-lactam antibiotics. MATERIALS AND METHODS: We studied 247 adult patients with invasive pneumococcal pneumonia occurring from 1997 to 2001. The following data were recorded from each patient: socio-demographic characteristics, underlying diseases, clinical presentation, initial severity of pneumonia, initial and subsequent antimicrobial therapy, in-hospital complications, hospital mortality and length of hospital stay. Multivariate analysis was done to identify variables associated with the development of pneumonia caused by a non-susceptible strain. RESULTS: The overall presence of penicillin non-susceptibility was 26.7%; no strain had an MIC >2 mg/L. Overall mortality was 23.5% in patients with pneumonia caused by intermediately resistant pneumococci and 12.7% in those with pneumonia caused by susceptible strains (P=0.075). Mortality during the first 7 days of admission, considered to be pneumonia-related deaths (13.7% versus 9.9%; P=0.448) was similar in both groups. The multivariate analysis showed that serotype 14 (OR, 140.18; 95% CI, 16.95-1159.20), serotype 19 (OR, 7.53; 95% CI, 1.98-28.7), haematological malignancy or splenectomy (OR, 4.46; 95% CI, 1.5-13.23) and HIV infection (OR, 4.54; 95% CI, 1.54-13.44) were the only independent factors associated with pneumonia caused by penicillin intermediately resistant pneumococci. In patients with strains having MICs of 0.1-1 mg/L, overall mortality was similar in the group of penicillin-treated patients (22.2%) to those treated with broad-spectrum beta-lactams (23.5%). CONCLUSIONS: There is a non-significant trend to higher mortality in patients with pneumococcal pneumonia caused by intermediately resistant strains; however, they do not have a poorer outcome when they are treated with amoxicillin.

Invasive pneumococcal disease in patients infected with HIV: still a threat in the era of highly active antiretroviral therapy.

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).