Sulfamethizole attenuates poloxamer 407-induced atherosclerotic neointima formation via inhibition of mTOR in C57BL/6 mice.

Mammalian target of Rapamycin C1 (mTORC1) inhibition limits plaque progression in atherosclerosis. The present study evaluated the protective effect of sulfamethizole on poloxamer 407-induced atherosclerotic neointima formation in C57BL/6 mice via mTOR inhibition. Poloxamer 407 (P-407) (0.5 g/kg body weight) was administered intraperitoneally to male C57BL/6 mice every third day for 148 days to induce chronic hyperlipidemia. From Day 121 to 148, animals were additionally administered Sulfamethizole (5, 10, and 50 mg/kg, p.o.), Rapamycin (0.5 mg/kg, positive control), or vehicle (1 ml/kg). Plasma lipid levels were measured on Days 120 and 148. Upon sacrifice, histological studies were performed, and aortic tissue interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and mTOR levels were evaluated. A molecular docking study was carried out to mimic the interaction of sulfamethizole with mTOR protein. Chronic P-407 administration significantly (p < 0.001) elevated plasma lipid levels, compared with those of the normal control group. Chronic hyperlipidemia resulted in increased tunica intima thickness, collagen deposition, and IL-6, TNF-α, and mTOR levels. Treatment with Sulfamethizole attenuated these parameters significantly in a dose-dependent manner. Molecular docking studies showed a significant interaction of Sulfamethizole with mTOR. In conclusion, this study suggests that sulfamethizole significantly limits poloxamer 407-induced atherosclerotic neointima formation in C57BL/6 mice via mTOR inhibition.

In utero exposure to antibiotics and risk of congenital malformations: a population-based study.

BACKGROUND: Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with the use of other commonly prescribed antibiotics. OBJECTIVE: To determine the risk of congenital malformations following first-trimester in utero exposure to 10 commonly prescribed antibiotics in Denmark. MATERIALS AND METHODS: This was a cohort study comprising all singleton liveborn children in Denmark between 2000 and 2015. Data on malformations were collected through 2016. Merging validated and comprehensive populationwide Danish healthcare and civic registries, we merged data on pregnancy, prescription drugs purchases during first trimester and congenital malformations. Using logistic regression, we calculated the odds ratio for congenital malformations (any), major congenital malformations, and cardiac congenital malformations for the 10 most commonly prescribed antibiotics (excluding 4 penicillins that served as control). In the primary analysis, the exposed cohort was compared to a cohort exposed to any of 4 penicillins considered safe during pregnancy (ampicillin, pivampicillin, benzylpenicillin, and phenoxymethylpenicillin). In sensitivity analysis, the exposed cohort was compared to an unexposed cohort. Covariate adjustments were made for maternal age at delivery, year of delivery, parity, pre-pregnancy body mass index, smoking, educational status, employment status, and annual personal income. RESULTS: We found no increased risk of congenital malformations to be related to first-trimester in utero exposure to the 10 most commonly prescribed antibiotics in Denmark compared to a cohort of pregnant women exposed to penicillins that are considered safe during pregnancy. Compared to unexposed pregnancies, small increased risks for major malformations and cardiac malformations were apparent for pivmecillinam (odds ratio, 1.13; confidence interval, 1.06-1.19; and odds ratio, 1.15; confidence interval, 1.04-1.28, respectively), sulfamethizole (odds ratio, 1.15; confidence interval, 1.07-1.24; and odds ratio, 1.22; confidence interval, 1.07-1.39, respectively), and azithromycin (odds ratio, 1.19, confidence interval, 1.03-1.38; and odds ratio, 1.29, confidence interval, 0.99-1.67, respectively). CONCLUSION: In this large populationwide cohort study, we found, with a high degree of precision, no increased risk of congenital malformations following first-trimester exposure to 10 commonly prescribed systemic antibiotics.

Revival of old antibiotics: needs, the state of evidence and expectations.

The gap between the emergence of antibiotic resistance and new antibiotic development has drawn attention to old antibiotics whose spectrum of coverage frequently comprises highly resistant bacteria. However, these antibiotics have frequently not undergone the structured process of antibiotic development of modern antibiotics, from pharmacokinetic/pharmacodynamic (PK/PD) studies establishing safe and effective dosing, establishment of susceptibility breakpoints, to clinical trials establishing clinical safety and effectiveness. In this review, we highlight the gaps for which we need old antibiotics in community- and hospital-acquired infections. Reviewing recently published and ongoing randomised controlled trials (RCTs) shows advances in our understanding of the efficacy and effectiveness of oral fosfomycin, mecillinam and nitrofurantoin for cystitis, and of trimethoprim/sulfamethoxazole for complicated skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the community. Summarising older evidence shows the inferiority of chloramphenicol versus modern antibiotics for severe infections. We lack studies on severe infections caused by carbapenem-resistant Gram-negative bacteria and other multidrug-resistant (MDR) bacteria in hospitalised and critically ill patients; ongoing studies assessing colistin and intravenous fosfomycin might fill in some gaps. In the re-development process of old antibiotics, we mandate modern PK/PD studies comprising special populations as well as RCTs addressing the target population of patients in need of these antibiotics powered to examine patient-relevant outcomes. Structured antibiotic re-development from the laboratory to evidence-based treatment recommendations requires public funding, multidisciplinary collaboration, international co-ordination, and methods to streamline the recruitment of critically ill patients infected by MDR bacteria.

Aspergillus Terreus Brain Abscess Complicated by Tension Pneumocephalus in a Patient with Angiosarcoma.

BACKGROUND Aspergillus terreus is an evolving opportunistic pathogen, and patients with A. terreus often have poor outcomes due to its intrinsic resistance to several systemic antifungal agents. Here we present a unique case of intracranial abscesses of A. terreus in a patient with recurrent angiosarcoma, complicated by development of tension pneumocephalus. CASE REPORT A 67-year old gentleman with history of scalp angiosarcoma with wide excision two years prior presented to the hospital for left arm clumsiness, altered mental status, and low-grade fever. Staphylococcus aureus and Proteus mirabilis bacteremia was detected, and Computed Tomography (CT) of the head showed right frontal lobe abscesses. He was started on steroids, intravenous vancomycin and cefepime, and was eventually discharged. He presented to the hospital again due to persistent and worsening symptoms. MRI showed progression of the brain lesions, and surgical biopsy and culture of lesions revealed A. terreus and gram-positive cocci. He was started on trimethroprim/sulfamethoxazole and voriconazole and symptoms improved. On post-op day four, he acutely decompensated with total loss of left arm strength; MRI demonstrated tension pneumocephalus. Conservative management was undertaken with continuous supplemental oxygen. Serial x-ray imaging over the next week demonstrated resolution of the pneumocephalus, and the patient was able to regain all proximal lower and upper extremity strength. CONCLUSIONS Never before has a case of A. terreus been associated with angiosarcoma or tension pneumocephalus in the literature. Proper identification and prompt diagnosis of species is crucial in the immunocompromised patient. Tension pneumocephalus should be included in the differential diagnosis of nontraumatic hemiparesis for emergent evaluation and management.

Prevalence of antibiotic susceptibility and resistance of Escherichia coli in acute uncomplicated cystitis in Korea: Systematic review and meta-analysis.

BACKGROUND: The aim of this study is to determine the prevalence of antibiotic susceptibility and resistance of Escherichia coli Escherichia coli (E coli) in female uncomplicated cystitis in Korea using meta-analysis. METHODS: A cross-search of the literature was performed with MEDLINE for all relevant data published before October 2015 and EMBASE from 1980 to 2015, the Cochrane Library, KoreaMed, RISS, KISS, and DBPia were also searched. Observational or prospective studies that reported the prevalence of antimicrobial susceptibility and resistance of E coli were selected for inclusion. No language or time restrictions were applied. We performed a meta-analysis using a random effects model to quantify the prevalence of antimicrobial susceptibility and resistance of E coli. RESULTS: Ten studies were eligible for the meta-analysis, which together included a total of 2305 women with uncomplicated cystitis. The overall resistance rate to antibiotics was 0.28 (95% confidence interval [CI]: 0.25, 0.32). The pooled resistance rates were 0.08 (95% CI: 0.06, 0.11) for cephalosporin, 0.22 (95% CI: 0.18, 0.25) for fluoroquinolone (FQ), and 0.43 (95% CI: 0.35, 0.51) for trimethoprim/sulfamethoxazole (TMP/SMX). Regression analysis showed that resistance to FQ is increasing (P = 0.014) and resistance to TMP/SMX is decreasing (P = 0.043) by year. The generation of cephalosporin was not a significant moderator of differences in resistance rate. CONCLUSION: The resistance rate of FQ in Korea is over 20% and is gradually increasing. Although the resistance rate of TMP/SMX is over 40%, its tendency is in decreasing state. Antibiotic strategies used for the treatment of uncomplicated cystitis in Korea have to be modified.

Drug-induced Hypersensitivity Syndrome Accompanied by Pulmonary Lesions Exhibiting Centrilobular Nodular Shadows.

A 51-year-old woman diagnosed with Crohn's disease developed drug-induced hypersensitivity syndrome (DIHS) 12 and six weeks after starting the oral intake of mesalazine and trimethoprim/sulfamethoxazole, respectively. Chest CT showed centrilobular nodular shadows and a transbronchial lung biopsy (TBLB) revealed infiltration of inflammatory cells predominantly in the small pulmonary artery walls and bronchiolar walls. Regarding pulmonary lesions of DIHS, infiltrative shadows have sometimes been reported, whereas nodular shadows have rarely been documented. This is a valuable case report for considering the mechanism underlying the development of pulmonary lesions in case of DIHS.

Development of amino- and dimethylcarbamate-substituted resorcinol as programmed cell death-1 (PD-1) inhibitor.

Blockading the interaction of programmed death-1 (PD-1) protein with its ligands (PD-Ls, such as PD-L1) was proved to be a pathway for suppressing the development of tumors and other degradations of biological species. Thus, finding PD-1 inhibitors situated at the convergence point of drug discovery. In addition to some monoclonal antibodies applied to treat cancers clinically, the screening of organic molecules for hindering the interaction of PD-1 with PD-L1 became an efficient strategy in the development of PD-1 inhibitors. We herein applied resorcinol and 3-hydroxythiophenol as the core to link with N,N-dimethylcarbamate and other alkyl-substituted amines to afford 13 amine-appended phenyl dimethylcarbamates (AAPDs). The test for blockading the combination of PD-1 with PD-L1 revealed that abilities of 13 AAPDs were higher than that of sulfamethizole, a successful PD-1 inhibitor. In particular, large hydrophobic substituents at amine moiety or a nitro at resorcinol skeleton enhanced the inhibitory effect of AAPD even higher than that of sulfamethoxypyridazine, another successful PD-1 inhibitor. The present results may provide valuable information for further investigation on synthetic PD-1 inhibitors.

Molecularly Imprinted Polymer Integrated with a Surface Acoustic Wave Technique for Detection of Sulfamethizole.

The synergistic effect of combining molecular imprinting and surface acoustic wave (SAW) technologies for the selective and label-free detection of sulfamethizole as a model antibiotic in aqueous environment was demonstrated. A molecularly imprinted polymer (MIP) for sulfamethizole (SMZ) selective recognition was prepared in the form of a homogeneous thin film on the sensing surfaces of SAW chip by oxidative electropolymerization of m-phenylenediamine (mPD) in the presence of SMZ, acting as a template. Special attention was paid to the rational selection of the functional monomer using computational and spectroscopic approaches. SMZ template incorporation and its subsequent release from the polymer was supported by IR microscopic measurements. Precise control of the thicknesses of the SMZ-MIP and respective nonimprinted reference films (NIP) was achieved by correlating the electrical charge dosage during electrodeposition with spectroscopic ellipsometry measurements in order to ensure accurate interpretation of label-free responses originating from the MIP modified sensor. The fabricated SMZ-MIP films were characterized in terms of their binding affinity and selectivity toward the target by analyzing the binding kinetics recorded using the SAW system. The SMZ-MIPs had SMZ binding capacity approximately more than eight times higher than the respective NIP and were able to discriminate among structurally similar molecules, i.e., sulfanilamide and sulfadimethoxine. The presented approach for the facile integration of a sulfonamide antibiotic-sensing layer with SAW technology allowed observing the real-time binding events of the target molecule at nanomolar concentration levels and could be potentially suitable for cost-effective fabrication of a multianalyte chemosensor for analysis of hazardous pollutants in an aqueous environment.

Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis.

Retinal hemorrhages and intermediate uveitis in a patient with drug reaction with eosinophilia and systemic symptoms syndrome: a case report.

PURPOSE: To report a case of drug reaction (or rash) with eosinophilia and systemic symptoms syndrome in association with intraretinal hemorrhages and intermediate uveitis. METHODS: Single case report. RESULTS: A 22-year-old Hispanic woman developed a facial rash and blurry vision after the use of oral trimethoprim-sulfamethoxazole for a urinary tract infection. Fundus examination revealed bilateral +2 vitritis and intraretinal hemorrhages in all four quadrants. An oral mucosal biopsy revealed V-shaped coagulative necrosis, intraepithelial and superficial acute and lymphoplasmacytic inflammation, consistent with drug hypersensitivity reaction. CONCLUSION: Drug reaction (or rash) with eosinophilia and systemic symptoms syndrome can present as cutaneous rash, mucosal lesions, eosinophilia, intermediate uveitis, and intraretinal hemorrhages. In such cases, vitreoretinal manifestations may be considered as diagnostic criteria instead visceral involvement.

Furoic and mefenamic acids as new matrices for matrix assisted laser desorption/ionization-(MALDI)-mass spectrometry.

The present study introduces two novel organic matrices for matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) for the analysis of small molecules. The first matrix is "2-amino-4,5-diphenylfuran-3-carboxylic acid" (also called furoic acid, FA) which was synthesized and then characterized by ultraviolet (UV), infrared (FTIR), nuclear magnetic resonance NMR ((1)H and (13)C) and mass spectrometry. The compound has organic semiconductor properties and exhibits intense UV-absorption which is suitable for the UV-MALDI laser (N2 laser, 337 nm). The second matrix is mefenamic acid (MA). The two matrices can be successfully applied for various classes of compounds including adenosine-5'-triphosphate (ATP, 0.5 µL(10.0 nmol)), spectinomycin (spect, 0.5 µL(14.0 nmol)), glutathione (GSH, 0.5 µL(9.0 nmol)), sulfamethazole (SMT, 0.5 µL(2.0 nmol)) and mixture of peptides gramicidin D (GD, 0.5µL (9.0 nmol)). The two matrices can effectively absorb the laser energy, resulting in excellent desorption/ionization of small molecules. The new matrices offer a significant enhancement of ionization, less fragmentation, few interferences, nice reproducibility, and excellent stability under vacuum. Theoretical calculations of the physical parameters demonstrated increase in polarizability, molar volume and refractivity than the conventional organic matrices which can effectively enhance the proton transfer reactions between the matrices with the analyte molecules. While the reduction in density, surface tension and index of refraction can enhance homogeneity between the two new matrices with the analytes. Due to the sublimation energy of mefenamic acid is (1.2 times) higher than that of the DHB, it is more stable to be used in the vacuum.

Pharmacophore modeling, homology modeling, and in silico screening reveal mammalian target of rapamycin inhibitory activities for sotalol, glyburide, metipranolol, sulfamethizole, glipizide, and pioglitazone.

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and member of the PI3K-related kinase (PIKK) family. It plays a central role in integrating signals from metabolism, energy homeostasis, cell cycle, and stress response. Aberrant PI3K/mTOR activation is commonly observed in diseases such as cancer, diabetes and Alzheimer's disease. Accordingly, we developed common feature binding hypotheses for a set of 6 potent mTOR antagonists. The generated models were validated using receiver operating characteristic (ROC) curve analyses. To gain better insight into ligand-mTOR interactions, a homology model for the kinase domain of mTOR was built using the crystallographic structure of PI3Kγ as template. The optimal pharmacophore model was further improved based on detailed docking studies of potent training compound in the homology model. The modified binding model was employed as 3D search query to screen our in-house-built database of established drugs. Subsequent in vitro screening of captured hits showed that six of them have submicromolar to low micromolar bioactivities, namely, glyburide, metipranolol, sulfamethizole, glipizide, pioglitazone, and sotalol.

The modified Cincinnati procedure: combined conjunctival limbal autografts and keratolimbal allografts for severe unilateral ocular surface failure.

PURPOSE: To describe the technique and present the outcomes of combined conjunctival limbal autografts (CLAU) and keratolimbal allografts (KLAL) for the treatment of unilateral severe ocular surface failure. METHODS: Interventional case series. Eleven eyes of 11 patients who sustained chemical burns (4 alkali and 2 acid) and combined chemical/thermal burns (5 eyes) from firework explosions had combined CLAU/KLAL surgery. Keratoplasty was performed subsequently for residual corneal stromal scarring limiting visual acuity. Inclusion criteria included eyes with severe unilateral total ocular surface failure, controlled glaucoma, and reasonable eyelid apposition with no exposure. Exclusion criteria included patients with any ocular surface abnormality in the fellow eye and those with contraindications to systemic immunosuppression (SI). Outcome measures included Snellen best-corrected visual acuity (BCVA), ocular surface stability, SI exposure, and complications. RESULTS: Preoperative BCVA was 20/400 or worse in all eyes. At the final follow-up (mean, 35.8 months; range, 12.1-105.9 months), 73% (8 of 11) eyes had BCVA of 20/80 or better (range, 20/25 to counting fingers), and ocular surface was stable in 82% (9 of 11). Ninety-one percent (10 of 11) had additional penetrating keratoplasty (PK) with a 60% (6 of 10 eyes) success rate. Three cases had subsequent Boston type 1 keratoprosthesis implantation after PK failure, and the fourth patient, at the time of his last follow-up visit, did not want further intervention for his edematous PK, which was a result of noncompliance-related corneal rejection. In eyes with more than 2 years of follow-up, SI was tapered at a mean of 16 months (range, 8-28 months). There were no intraoperative complications. No secondary tumors, cardiac events, or deaths occurred while patients were on SI. One patient developed secondary glaucoma refractory to medical management after subsequent PK, requiring cyclodiode laser. CONCLUSIONS: Combined CLAU/KLAL and staged keratoplasty is effective in improving vision and maintaining long-term ocular surface stability in patients with severe unilateral ocular surface disease and conjunctival deficiency.

Outcomes of moderate-to-severe Pneumocystis pneumonia treated with adjunctive steroid in non-HIV-infected patients.

While it is well-known that adjunctive corticosteroid use improves the outcome of moderate-to-severe Pneumocystis jirovecii pneumonia (PcP) in patients with human immunodeficiency virus (HIV), there are limited data on its efficacy in non-HIV-infected patients with PcP. Patients undergoing fiber-optic bronchoscopy with bronchoalveolar lavage for suspected PcP from January 2007 through December 2010 were reviewed retrospectively. We compared demographics, clinical characteristics, and outcomes in 88 non-HIV-infected patients with moderate-to-severe PcP with (n = 59) and without (n = 29) adjunctive corticosteroid use. Outcomes of PcP were assessed by respiratory failure and 30-day and 90-day all-cause mortality. Survival curves were analyzed by the Kaplan-Meier method and estimated by the log rank test. All-cause mortality of moderate-to-severe PcP at 90 days was lower in the solid-organ transplant recipients than in all other patients (6/26 [23%] versus 34/62 [55%], respectively; P = 0.006), and mortality at 30 days was lower in patients with hematologic malignancies than in all other patients (4/26 [15%] versus 24/62 [39%], respectively; P = 0.03). The outcomes of PcP were not significantly different in moderate-to-severe PcP patients with and without adjunctive corticosteroid use, regardless of recent corticosteroid use. Survival analysis of PcP patients with and without corticosteroid use by the Kaplan-Meier method also did not reveal any difference (log rank test; P = 0.81). There again was no difference within the subgroup of PcP patients with solid-organ transplants. Adjunctive corticosteroid use may not improve the outcome of moderate-to-severe PcP in non-HIV-infected patients.

[Colonic malacoplakia treated with sulfamethizole and trimethoprim]. / Malokoplaki i colon behandlet med sulfamethizol og trimetoprim.

We report a case of colonic malacoplakia in a 78-year-old woman, developed following short-term treatment with prednisolone. Clinically, the patient presented with diarrhoea (up to ten times a day) and malaise. Laboratory tests revealed severe anaemia and elevated inflammatory parameters. Colonoscopy showed macroscopic yellowish nodular changes throughout the colon. Biopsies were diagnostic for malacoplakia and exhibited moderate growth of Escherichia faecium and ciprofloxacin-resistant Escherichia coli. The condition resolved during three months of antibiotic treatment with sulfamethizole and trimethoprim.

[Of bugs and joints. Oligoarthritis caused by Tropheryma whipplei]. / Oligoarthritis durch Tropheryma whipplei. "Of bugs and joints".

Whipple's disease is a rare, chronic infection caused by Tropheryma whipplei, an ubiquitary gram positive bacterium. The disease is associated with a high mortality in absence of an antibiotic treatment. The disease can be detected in affected tissues and body fluids by light and electron microscopy, as well as by polymerase chain reaction (PCR). Musculoskeletal symptoms such as arthralgia and arthritis frequently represent the first manifestation of this multi-system disease; typical subsequent symptoms are weight loss, diarrhea, and abdominal pain. Symptoms of central nervous system involvement are present in 10-40% of cases. We report on a 67 year-old male with a history of migratory oligoarthritis over three decades in whom the causative agent was detected by PCR in synovial fluid only. This case illustrates that searches for the characteristic PAS-positive macrophages and PCR in biopsies from the duodenum may be insufficient and that diagnostic efforts should be complemented with PCR assays from affected tissues or body fluids. It is recommended that antibiotic treatment be carried out with an agent that penetrates well into the cerebrospinal fluid, e.g. ceftriaxone, followed by cotrimoxazole. Antibiotics should be maintained over several months to years. It is prudent to document the disappearance of the pathogen in the affected compartments prior to the discontinuation of the antibiotic therapy.

Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: a randomized controlled trial.

OBJECTIVE: To investigate whether short-term treatment with pivmecillinam was more effective than sulfamethizole in patients with acute uncomplicated urinary tract infection (UTI). DESIGN: Randomized controlled trial. SETTING: General practice, Denmark. SUBJECTS: Patients (n = 167) with uncomplicated UTI confirmed by positive urine phase-contrast microscopy. MAIN OUTCOME MEASURES: Drug efficacy based on clinical and bacteriological cure. RESULTS: Urinary symptoms disappeared first in patients treated with pivmecillinam, but after five days there was no significant difference in clinical cure rate between the two antibiotics. At the follow-up visit 7-10 days after initiation of treatment, 95.4% of patients treated with pivmecillinam and 92.6% of patients treated with sulfamethizole had no persistent cystitis symptoms (difference 2.8%, CI -4.5%; 10.0%). Bacteriological cure was observed in 68.8% of patients randomized to pivmecillinam and in 77.9% randomized to sulfamethizole (difference -9.2%, CI -24.7%; 6.3%). Some 26.8% of patients randomized to pivmecillinam experienced a new UTI within 6 months after treatment compared with 18.4% of patients randomized to sulfamethizole (difference 8.4%, CI -4.5%;21.4%). No patients developed septicaemia with urinary pathogens within one year after initial treatment. CONCLUSION: Patients treated with a three-day regime of pivmecillinam experienced faster relief of symptoms compared with patients treated with a three-day regime of sulfamethizole. Five days after initiation of treatment there was no significant difference in clinical and bacteriological cure between the two antibiotic regimes.

[What are we learning about Staphylococcus saprophyticus?]. / Qué estamos aprendiendo de Staphylococcus saprophyticus?

INTRODUCTION: Staphylococcus saprophyticus is frequent cause of urinary tract infection in women; hence, it is important to know the epidemiology and antibiotic susceptibility of this microorganism. METHOD: A retrospective longitudinal study was performed in urine specimens from outpatients in our health area cultured in the Microbiology Laboratory of C.E. Argüelles (Madrid, Spain) over a 10-year period (1997-2006). RESULTS: Among 35,136 urine cultures with a significant count, we identified 331 S. saprophyticus (0.9%); 324 in women and 7 in men. Mean age of the infected patients was 32.7 years. A total of 83.9% of the strains were in women aged 15 to 44 years (37 women in this group were pregnant) and the largest numbers of isolates were found during the months of June and November. All S. saprophyticus strains were susceptible to vancomycin, rifampin, gentamicin and amoxicillin-clavulanic acid. Of note, there was a high percentage of resistance to erythromycin (37.7%) (96% consistent with the MSB phenotype) which has significantly increased since 1997 (P < 0.05); 1.5% were also resistant to clindamycin. Only 0.9% were resistant to fluorquinolones. Resistance to chloramphenicol, trimethoprim/sulfamethoxazole, and penicillin was 3.9%, 6%, and 55.6%, respectively. Based on the 2006 CLSI guidelines, 45% of S. saprophyticus isolates were considered oxacillin-resistant. CONCLUSION: These results suggest the following: First, S. saprophyticus should be considered among agents causing urinary tract infection in women 15 to 44 years old, including pregnant women, particularly during spring and autumn. Second, cotrimoxazole may be an excellent option for treating cystitis in patients without risk factors. Third, almost half of S. saprophyticus strains were considered oxacillin-resistant, thereby denying the benefit of treatment with oral beta-lactams in urinary tract infections. This is especially important in pregnant women, who should avoid trimethoprim/sulfamethoxazole and quinolones (FDA Group C), as well as fosfomycin, with in vitro resistance.