Optimized fosfomycin regimens for treating carbapenem-resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function.

Fosfomycin has been used to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20-24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 µg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 µg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.

Intravenous fosfomycin indications and treatment outcomes in pediatric usage: analysis from a single center in Turkey.

Current data on fosfomycin usage in children are limited. We present data on the clinical use of intravenous (IV) fosfomycin in children. Hospitalized patients who received ≥3 days of IV fosfomycin between April 2021 and March 2023 were analyzed retrospectively. Forty-three episodes of infection in 39 patients were evaluated. The mean age of the patients was 5.35 (10 days to 17.5 years) years, and 54% were male. Infections were hospital-acquired in 79% of the episodes. Indications for fosfomycin were urinary tract infection (35%), bacteremia (32.6%), catheter-related bloodstream infection (16.3%), soft tissue infection (4.7%), sepsis (4.7%), surgical site infection (2.3%), burn infection (2.3%), and pneumonia (2.3%). Klebsiella pneumoniae was identified in 46.5% of the episodes, and a pan-drug or extensive drug resistance was detected in 75% of them. Carbapenem was used before fosfomycin at significantly higher rates in K. pneumoniae episodes (P = .006). Most (88.5%) patients received fosfomycin as a combination therapy. Culture negativity was achieved in 80% of episodes within a median treatment period of 3 (2-22) days, which was significantly shorter in K. pneumoniae episodes (P < .001). Treatment-related side effects were seen in 9.3% of the episodes. Side effects were significant after 3 weeks of treatment (P = .013). The unresponsivity rate to fosfomycin was 23.3%. Nine (21%) of the patients who were followed up in the intensive care units mainly died because of sepsis (56%). IV fosfomycin is an effective agent in treating severe pediatric infections caused by resistant microorganisms. Fosfomycin can be used in various indications and is generally safe for children.

Combination therapy with IV fosfomycin for adult patients with serious Gram-negative infections: a review of the literature.

Treatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic/pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria. Data from dynamic in vitro and animal infection model studies of highly resistant Enterobacterales and non-lactose fermenters are positive and suggest IV fosfomycin in combination with a ß-lactam, polymyxin or aminoglycoside produces a synergistic effect that rivals or surpasses that of other aminoglycoside- or polymyxin-containing regimens. Clinical studies performed to date primarily have involved patients with pneumonia and/or bacteraemia due to Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii. Overall, the observed success rates with fosfomycin combination regimens were consistent with those reported for other combination regimens commonly used to treat these patients. In studies in which direct treatment comparisons can be derived, the results suggest that patients who received fosfomycin combination therapy had similar or improved outcomes compared with other therapies and combinations, especially when it was used in combination with a ß-lactam that (1) targets PBP-3 and (2) has exceptional stability in the presence of ß-lactamases. Collectively, the data indicate that combination therapy with IV fosfomycin should be considered as a potential alternative to aminoglycoside or polymyxin combinations for patients with antibiotic-resistant Gram-negative infections when benefits outweigh risks.

The use of fosfomycin in infections caused by multidrug-resistant pathogens, especially pneumonia in children: a five-year retrospective single-centre experience.

BACKGROUND: Fosfomycin is gaining increasing attention for its activity against MDR or XDR pathogens. Currently, IV fosfomycin is a potential option for treating various infections, including urinary tract infections, pneumonia and skin infections when first-line treatments fail. OBJECTIVES: To evaluate the demographic, clinical, microbiological and treatment modality of children received IV fosfomycin to treat infections caused by MDR pathogens since there are few data on the use of fosfomycin in children. METHODS: This study was conducted retrospectively with patients under 18 years of age who were treated with IV fosfomycin for at least 72 h due to infections caused by MDR pathogens between January 2019 and October 2023 at Marmara University Pendik Training and Research Hospital, Istanbul, Türkiye. Data on demographic and clinical features, microbiological findings, treatment modalities and side effects were evaluated. RESULTS: Twenty-five children, for a total of 32 cases of infection episodes, with a mean age of 11.4 ±â€Š3.92 years who received IV fosfomycin were included. The most frequent comorbidity was chronic pulmonary diseases, and the most common infection needed for IV fosfomycin was MDR Pseudomonas aeruginosa pneumonia. In all cases, fosfomycin was administered in combination with other antibiotics, mainly meropenem-colistin (68.7%) or meropenem (15.6%). Twenty-two (71.9%) cases had favourable clinical responses at the end of therapy. CONCLUSIONS: Our results suggest that IV fosfomycin may be an effective treatment option for MDR pathogens in the paediatric population. Nevertheless, careful stewardship is necessary to maintain efficacy and reduce antimicrobial resistance selection risk.

Using fosfomycin to prevent infection following ureterorenoscopy in response to shortage of cephalosporins: a retrospective preliminary study.

BACKGROUND: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. METHODS: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. RESULTS: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. CONCLUSIONS: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.

Individual health insurance data of antibiotic delivery in previous months as a tool to predict bacterial resistance of urinary tract infection: A prospective cohort study.

OBJECTIVES: We aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months. PATIENTS AND METHODS: French patients were prospectively recruited in two centers in 2015-2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files. RESULTS: Previous antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20-2.21], 1.59 [1.02-2.48], 3.01 [1.90-4.77], and 2.60 [1.75-3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41-1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18]). CONCLUSIONS: Resistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: A Propensity Score Adjusted Retrospective Cohort Study.

BACKGROUND: The role of intravenous fosfomycin (iv-FOS) as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI) needs to be evaluated in clinical practice, as in vitro data show potential efficacy. METHODS: All consecutive patients with a GNB-BSI from 01 January 2021 to 01 April 2023 were included. Primary outcome was 30-day mortality. A Cox regression analysis was used to identify predictors of mortality; an inverse-probability of treatment-weighting (IPTW) analysis was also performed. RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson comorbidity index of 5 (3-7). At GNB-BSI onset, the median SOFA score was 5 (2-7) and 122 patients (34%) presented with septic shock. Pathogens were principally Klebsiella pneumoniae (42%), Escherichia coli (28%) and Pseudomonas aeruginosa (17%); of them, 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); a combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) g/daily. The use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, P = 0.147). However, on multivariable Cox-regression, combination therapy with iv-FOS resulted in protection for mortality (aHR 0.51, 95% CI 0.28-0.92), but not other combo-therapies (HR 0.69, 95% CI 0.44-1.16). This result was also confirmed with the IPTW-adjusted Cox model (aHR 0.52, 95% CI 0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA > 6, PITT ≥ 4) and when iv-FOS was initiated within 24 hours of GNB-BSI onset. CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role in improving survival. These results justify the development of further clinical trials.

Adverse events during intravenous fosfomycin therapy in a real-life scenario. Risk factors and the potential role of therapeutic drug monitoring.

BACKGROUND: Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting. PATIENTS AND METHODS: Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated. RESULTS: Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0-7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09-2.31), 1.46 (95%CI:1.03-2.07) and 1.73 (95%CI:1.27-2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44-0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39-0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css. CONCLUSIONS: We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs. KEY POINTS: Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.

Effect of fosfomycin-induced hypernatremia on patients' hospital stay length and survival.

BACKGROUND AND OBJECTIVE: Hypernatremia is a possible side effect of intravenous fosfomycin. The aim of this study was to investigate the effects of changes in sodium (Na) levels on hospital stay and survival in patients hospitalized in the intensive care unit receiving fosfomycin. SUBJECTS AND METHODS: This study was conducted retrospectively on the files of patients over the age of 60, who were admitted to the Internal Medicine Intensive Care Unit. Plasma sodium levels were observed and documented over a period of 14 days. The patients were divided into two groups (Hypernatremia group Na > 145 mEq/L vs normonatremia group 135-145 mEq/L). In addition, daily sodium changes were noted for 14 days in patients. RESULTS: The mean age of the patients was 75 years. Hospitalization days were longer for hypernatremia patients (31.5 days vs 41 days, p = 0.003). Patients with hypernatremia had an extended duration of stay in the intensive care unit. (21 days vs 31 days p = 0.002). The 1-month survival rate was 61.4% in patients with hypernatremia and 24.9% in patients without hypernatremia (p = 0.004). The absence of hypernatremia increases mortality by 2.09 times (95% CI 1.35-3.23). When discharge and mortality rates were analyzed according to sodium fluctuation, discharged patients exhibited a lower sodium fluctuation (4 min/max (-10/19) vs 6 min/max (-16/32) p < 0.001). CONCLUSION: In conclusion, the strength of our study is that it specifically focuses on the consequences of the sodium fluctuation on patient management and provides results.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

BACKGROUND: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

FosA8-producing E. coli ST131: clinical cases in Italy, February 2023.

Fosfomycin-resistant FosA8-producing Enterobacterales are uncommon strains with extremely low incidence in Europe, based on only three reports in the literature. We detected FosA8-producing Escherichia coli ST131 in clinical isolates from two patients admitted in February 2023 to a rehabilitation unit in Italy. The occurrence of rare fosA-like genes in the high-risk clone ST131 is of clinical relevance. The dissemination of FosA-producing E. coli, although still at low levels, should be continuously monitored.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Comparison of ciprofloxacin versus fosfomycin versus fosfomycin plus trimethoprim/sulfamethoxazole for preventing infections after transrectal prostate biopsy.

BACKGROUND: To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX). METHODS: Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF). RESULTS: Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7-2.6) for group-C vs. group-BF and 2.8 (CI 1.4-5.7) for group-F vs. group-BF respectively. CONCLUSION: The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended.

Change in Tissue Microbiome and Related Human Beta Defensin Levels Induced by Antibiotic Use in Bladder Carcinoma.

It is now generally accepted that the success of antitumor therapy can be impaired by concurrent antibiotic therapy, the presence of certain bacteria, and elevated defensin levels around the tumor tissue. The aim of our current investigation was to identify the underlying changes in microbiome and defensin levels in the tumor tissue induced by different antibiotics, as well as the duration of this modification. The microbiome of the tumor tissues was significantly different from that of healthy volunteers. Comparing only the tumor samples, no significant difference was confirmed between the untreated group and the group treated with antibiotics more than 3 months earlier. However, antibiotic treatment within 3 months of analysis resulted in a significantly modified microbiome composition. Irrespective of whether Fosfomycin, Fluoroquinolone or Beta-lactam treatment was used, the abundance of Bacteroides decreased, and Staphylococcus abundance increased. Large amounts of the genus Acinetobacter were observed in the Fluoroquinolone-treated group. Regardless of the antibiotic treatment, hBD1 expression of the tumor cells consistently doubled. The increase in hBD2 and hBD3 expression was the highest in the Beta-lactam treated group. Apparently, antibiotic treatment within 3 months of sample analysis induced microbiome changes and defensin expression levels, depending on the identity of the applied antibiotic.

Treatment of infections caused by multidrug-resistant Gram-negative bacilli: A practical approach by the Italian (SIMIT) and French (SPILF) Societies of Infectious Diseases.

INTRODUCTION: The emergence of multidrug-resistant Gram-negative bacilli and the development of new antibiotics have complicated the selection of optimal regimens. International guidelines are valuable tools, but are limited by the scarcity of high-quality randomized trials in many situations. METHODS: A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, an updated literature review and open discussions. RESULTS: The panel reached consensus for the following 'first choices': (i) cefepime for ventilator-acquired pneumonia due to AmpC ß-lactamase-producing Enterobacterales; (ii) the ß-lactam/ß-lactamase inhibitor combination most active in vitro, or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to Pseudomonas aeruginosa resistant to ceftolozane-tazobactam; (iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion) for complicated urinary tract infections (cUTIs) caused by extended-spectrum ß-lactamase-producing Enterobacterales with piperacillin-tazobactam minimum inhibitory concentration (MIC) ≤8 mg/L; (iv) high-dose cefepime for cUTIs due to AmpC ß-lactamase-producing Enterobacterales other than Enterobacter spp. if cefepime MIC ≤2 mg/L; (v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to third-generation cephalosporin-resistant Enterobacterales; (vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo-ß-lactamase-producing Enterobacterales; (vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant Acinetobacter baumannii; (viii) meropenem-vaborbactam for BSIs caused by Klebsiella pneumoniae carbapenemase-producing Enterobacterales; and (ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa. CONCLUSIONS: These expert choices were based on the necessary balance between antimicrobial stewardship principles and the need to provide optimal treatment for individual patients in each situation.

Bacteriological profile, antimicrobial susceptibility, and factors associated with urinary tract infection in pregnant women.

INTRODUCTION: Urinary tract infection (UTI) is a common bacterial complication in pregnancy. The study aimed to estimate the prevalence, risk factors, and bacterial etiology of UTI during pregnancy and determine the efficacy of antimicrobial drugs in treating UTIs. METHODOLOGY: Urine specimens and clinical data were collected from pregnant women who attended primary health centers in Erbil, Iraq. All specimens were cultured on appropriate media and identified by standard microbiological methods. The pregnant women were grouped into symptomatic UTI group, asymptomatic bacteriuria group, and the control group. The agar dilution method was used to determine antimicrobial susceptibility. RESULTS: Among the 5,042 pregnant women included in this study, significant bacteriuria was found in 625 (12.40%) of the cases, and 198 (31.68%) had symptomatic UTI, of which 43.59% were diagnosed during the third trimester. Out of the 643 bacteria isolated, 33.28% were symptomatic UTI, of which 43.59% developed during the third trimester. There was a significant difference in the bacterial etiology between symptomatic UTI and asymptomatic bacteriuria (p = 0.002), as well as between cystitis and pyelonephritis (p = 0.017). The most common bacterial species isolated was Escherichia coli, which was susceptible to fosfomycin (100%), meropenem (99.45%), and nitrofurantoin (97.8%). CONCLUSIONS: Pregnant women are more likely to develop UTI in the third trimester. Escherichia coli is the predominant pathogen. The study suggests the use of fosfomycin, meropenem, and nitrofurantoin for the treatment of UTI. No Gram-positive isolates were resistant to daptomycin.

Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.

[Antibacterial prophylaxis with fosfomycin at the time of the urethral catheter removal after radical prostatectomy (prospective randomized trial)].

AIM: To evaluate the effect of antibacterial prophylaxis using oral fosfomycin during the removal of a urethral catheter after radical prostatectomy on the development of urinary tract infection, severity of leukocyturia and bacteriuria, as well as the severity of lower urinary tract symptoms. MATERIALS AND METHODS: A single-center, non-blind, prospective, randomized controlled trial was carried out. The main group included 40 patients, and the control group included 37 patients. In the group 1, patients received two doses of oral fosfomycin, 3 g, namely in the evening on the day of catheter removal (the first dose) and 48 hours after catheter removal (the second dose). In the group 2, patients did not receive any antibacterial prophylaxis after urethral catheter removal. The endpoints of the study were confirmed episodes of urinary tract infection within 1 month after removal of the urethral catheter, leukocyturia and bacteriuria in urinalysis/urine culture) and severity of the lower urinary tract symptoms assessed by IPSS questionnaire. RESULTS: In the group 2, urinary tract infection was noted in 17.1%, while in the group 2 only in 2.6% of patients (p=0.032). Leukocyturia and bacteriuria were significantly less common in the group receiving antibacterial prophylaxis with fosfomycin (18.4% vs. 48.6%, respectively; p=0.006). Positive urine culture was observed in 7.9% vs. 25.7%, respectively (p=0.035). Four weeks after removal of the urethral catheter, the average IPSS score was significantly higher in the group 2 (13.2 vs. 9.5 points; p=0.002). There were no cases of allergic reaction and pseudomembranous colitis associated with C. difficile in both groups. Diarrhea cured with sorbents was noted in 2 patients (5.2%) in fosfomycin group. CONCLUSION: Antibacterial prophylaxis using two oral doses of fosfomycin 3 g on the day of urethral catheter removal and 48 hours after catheter removal after radical prostatectomy appears to be an effective scheme that reduces the incidence of urinary tract infection and the severity of lower urinary tract symptoms, and is characterized by a minimal risk of adverse events. It is necessary to carried out further research and develop clear recommendations for antibacterial prevention in urological interventions requiring prolonged urethral catheterization.