Routine Antibacterial Prophylaxis Research Articles

Stopping antibacterial prophylaxis in pediatric allogeneic hematopoietic cell transplantation: An internal audit.

Antibacterial prophylaxis in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) is controversial and not recommended by international guidelines. We analyzed relevant posttransplant outcomes following discontinuation of antibacterial prophylaxis at a major European pediatric transplant center. The single-center retrospective audit included all pediatric allogeneic HCT patients (pts) transplanted between 2011 and 2020 before (≤2014) and after (≥2015) stopping routine antibacterial prophylaxis with penicillin, metronidazole, and ciprofloxacin upon start of the conditioning regimen. The primary endpoint was overall survival until the first hospital discharge. Secondary endpoints included the occurrence of fever; bacterial infections; and cumulative days with antibacterial agents until discharge. A total of 257 HCT procedures were performed in 249 pts (median age: 10 years, range, 0.2-22.5) for leukemia/lymphoma (n = 150) and nonmalignant disorders (n = 107). Of these, 104 procedures were performed before (cohort 1) and 153 after (cohort 2) stopping prophylaxis. Overall survival until discharge was 90.4% in cohort 1 and 96.1% in cohort 2 (p = .06). No differences were observed in the occurrence of fever (92.3vs. 94.1%; p = .57) and bacterial infections (34.6vs. 25.5%; p = .11). The median number of days on antibacterial agents was significantly lower in cohort 2 (39vs. 34; p = .002). Detection rates of resistant organisms were overall low. In this single-center audit, the stop of routine antibacterial prophylaxis had no effect on the occurrence of fever, bacterial infections, resistant organisms, and GVHD. Overall antibiotic use was significantly reduced, and survival was noninferior to the historical control cohort.

Antimicrobial prophylaxis and the rate of blood stream infections and Clostridioides difficile in pediatric stem cell transplantation: A single-center retrospective study.

The use of prophylactic antibiotics in the pre-engraftment period to minimize the risk of bacteremia is debatable given concerns of Clostridioides difficile (C.diff), antibiotics resistance, and disruption of gut microbiota. We retrospectively reviewed the rate and characteristics of bacteremia and C.diff infections within the first 100 days post-HSCT in all pediatric patients who received routine antibacterial prophylaxis during HSCT from 2015 to 2018. C.diff infection was defined by the presence of three or more unformed stools in 24h and positive stool test for C.diff or its toxins. One hundred and thirty-five (100 allogeneic and 35 autologous) transplants in 123 patients were eligible for analysis. Median age at transplant was 7.1 (range 0.2-13.7), 67 (55%) were women, and diagnosis was malignant condition in 68 patients. Median time to neutrophil engraftment was 18 days (13-23). Cefepime or piperacillin-tazobactam prophylaxis was used in 105 (78%) and 28 (21%) of patients, respectively. Only five (3%) patients had bacteremia during the pre-engraftment period, and 13 (11%) patients developed bacteremia postengraftment. Septic shock was present in only one patient pre-engraftment and was due to gram-negative bacteria. All patients who developed bacteremia received MAC. Thirteen patients (10%) of patients fulfilled C.diff infection definition. There was no mortality related to bacterial infections among our patients. The use of antibiotic prophylaxis was associated with low rate of bacteremia in the pre-engraftment period and a 10% risk of C.diff infections. More studies are needed to better evaluate the efficacy of antibiotic prophylaxis in HSCT patients.

Antifungal Prophylaxis for Adult Recipients of Veno-Venous Extracorporeal Membrane Oxygenation: A Cautionary Stance During the COVID-19 Pandemic.

Antifungal Prophylaxis for Adult Recipients of Veno-Venous Extracorporeal Membrane Oxygenation: A Cautionary Stance During the COVID-19 Pandemic.

Addition of doxycycline to ciprofloxacin for infection prophylaxis during autologous stem cell transplants for multiple myeloma.

The most commonly used antibacterial prophylaxis during autologous stem cell transplants (ASCT) for multiple myeloma (MM) involves a fluoroquinolone, such as ciprofloxacin or levofloxacin. We assessed the impact of adding doxycycline to ciprofloxacin as routine antibacterial prophylaxis in these patients. We retrospectively reviewed electronic medical records and our ASCT database to analyze rates and types of bacterial infections in MM patients who underwent ASCT in our institution. Among 419 patients, 118 received ciprofloxacin alone (cipro group), and 301 ciprofloxacin and doxycycline (cipro-doxy group). Neutropenic fever (NF) developed in 63 (53%) and 108 (36%) patients of the cipro and cipro-doxy groups, respectively (p = 0.010). The number of documented bacteremic episodes was 13 (11%) and 14 (4.7%) in the two groups, respectively (p = 0.017). Antimicrobial resistance and Clostridium difficile infections were uncommon. Transplant-related mortality was 1% in both groups. The addition of doxycycline to standard prophylaxis with ciprofloxacin seems to reduce the number of NF episodes and documented bacterial infections in patients with MM undergoing ASCT, without increasing rate of serious complications.

Fluoroquinolone prophylaxis for the prevention of central line-associated bloodstream infection in autologous stem cell transplant.

e19508 Background: Patients (Pts) undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line-associated bloodstream infection (CLABSI). Use of prophylactic antibiotics to prevent CLABSI in autologous SCT (autoSCT) is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSI in autoSCT. Methods: Pts undergoing autoSCT at the University of Pennsylvania received levofloxacin prophylaxis during a 6-month intervention period from 1/13/2016 - 7/12/2016. Levofloxacin was administered from autoSCT until day 13, absolute neutrophil count > 500/mm3, or febrile neutropenia. Outcomes were compared to a retrospective cohort who underwent autoSCT, but did not receive routine antibacterial prophylaxis during the previous year (1/13/2015 – 1/12/2016). The primary endpoint was incidence of CLABSI assessed using Cox proportional hazards regression. Results: A total of 243 pts underwent autoSCT, with 69 receiving levofloxacin prophylaxis during the intervention period. Median age was 59 yrs, 74% had multiple myeloma, and 58% received melphalan 200mg/m2. Median duration of neutropenia was 6 days. CLABSI rate was reduced from 18.4% during the baseline period to 7.3% during the intervention period ( P= 0.03). There were no significant differences in characteristics between the baseline and intervention groups except for liver disease (1% versus 5%, P= 0.03). On multivariable analysis, levofloxacin prophylaxis was associated with a significant reduction in CLABSI incidence (HR 0.33; 95% CI 0.12-0.88; P= 0.02), as was underlying multiple myeloma (HR 0.38; 95% CI 0.20-0.74; P= 0.004) and liver disease (HR 4.31; 95% CI 0.99-18.8; P= 0.05). There was also a reduction in neutropenic (NTP) fever (OR 0.21; 95% CI 0.11-0.38; P< 0.001) and a trend toward reduction in ICU transfer for sepsis (OR 0.13; 95% CI 0.01-1.39; P= 0.08) in patients receiving levofloxacin prophylaxis. There were no significant differences in rates of secondary BSIs, C. difficileinfection, or mortality. Conclusions: Levofloxacin prophylaxis was effective in reducing CLABSI and NTP fever in patients undergoing autoSCT.

Short Course of Levofloxacin During Neutropenia Prevents Early and Late Bacteremia Episodes After Allogeneic Blood and Marrow Transplantation (alloBMT)

Abstract 4141Bacteremia is a common complication after alloBMT due to neutropenia, mucositis, GvHD, immunosuppressive agents, and slower immune reconstitution and full chimerism after reduced intensity conditioning. Since symptoms and signs of bacteremia (e.g., fever) may be blunted or absent in BMT recipients receiving intensive immunosuppression, our clinical practice applies a low threshold for obtaining blood cultures. Our goals were to define risk factors for bacteremia at pre-specified periods after BMT and to compare rates of bacteremia using microbiological criteria vs. CDC/NHSN criteria which require symptoms and signs such as fever, chills or hypotension. We performed a retrospective cohort study of 168 adult (>18 yrs) consecutive first alloBMT patients from January 2008 to May 2012. A bacteremia episode (BE) was defined according to the EBMT Infectious Disease Working Party criteria which excludes skin flora contaminants. A second set of positive blood cultures of the same bacterial strain >30 days apart was considered a recurrent BE. Blood cultures which grew different bacterial strains were defined as a single episode of polymicrobial bacteremia if drawn < 48 hrs apart and as unique BEs if drawn > 48 hrs apart. Patient characteristics include: median (range) age 54 (19–73) yrs, 57% male, 49% AML, 14% ALL, 11% MDS, 7% NHL, 20% other diseases, 77% KPS 50–80, 81% peripheral blood, 64% unrelated donor, 23% <10/10 HLA match, 73% reduced intensity conditioning regimens. After 8/2011, all patients received levofloxacin prophylaxis during neutropenia, whereas before 8/2011, no routine antibacterial prophylaxis was used. At discharge, penicillin prophylaxis was initiated for all patients until at least 1 yr post-alloBMT. All patients received voriconazole or micafungin as anti-fungal prophylaxis from day -1 until off immunosuppression and acyclovir as anti-viral prophylaxis for at least 1 yr post-alloBMT. Overall, there were 238 BEs in 168 patients for a rate of 1.42 BE/pt. The rate of BEs was highest in the early peri-BMT period and dropped significantly after day+30 (Table), and 80% of BEs before day+30 occurred during neutropenia. The proportions of patients with >1 BE in each time period were 49%, 31%, and 28%, respectively. While 67% of BEs (defined by microbiological criteria), from admission (first day of conditioning regimen) to day+30 met CDC/NHSN criteria, only 25% of BEs after day+30 did so. The majority of BEs did not result in a central line replacement. From admission through 1 yr post-allo BMT, 59 (35%), 49 (29%) and 60 (36%) patients had 0, 1, and >1 cumulative total BEs, respectively. We performed a univariate analysis of risk factors including gender, age, KPS, diagnosis, donor relation, HLA match, SC type, use of levofloxacin as antimicrobial prophylaxis, and conditioning regimen intensity, for >1 BE for each of the 3 time periods, and cumulatively. Lack of levofloxacin prophylaxis was a significant risk factor for BEs in all time periods post-alloBMT. In addition, grade II-IV acute GvHD was a significant risk factor for >1 or >2 BEs in the day+31 to 100, day+101 to 365 and admission to day+365 time periods. Levofloxacin prophylaxis decreased the rate of patients with >1 BE from 54% to 14% in the day+30 time period (P<0.0001) and from 69% to 36% from admission to 1 yr post-alloBMT (P=0.003). BEs resulted in death within 7 days of first positive culture in 4 patients due to MRSA, E faecium, K pneumonia, and E faecalis/Candida. We observed the greatest discordance between applying microbiological criteria vs. CDC criteria to define BEs from days+31 to 365. This discordance reflects the lack of sensitivity of typical clinical signs/symptoms of infection in the setting of GvHD post-alloBMT, and points to the need for modified criteria to define BEs for this patient population. Development of improved prophylaxis strategies that focus on patients with GvHD may diminish the incidence and severity of these infections.Time Period# of BEs# pts with >=1 BE/# pts evaluable (%)# (%) of BEs meeting CDC criteria# (%) of BEs resulting in a CVC line changeTotal # of Observation Days# BEs/Observation DaysRate of BE/1000 pt-DaysAdmission to Day +309282 (49)62 (67)7 (8)5,9700.015415Day +31 to 1007051 (31)18 (26)10 (14)10,6930.00657Day +101 to 3657640 (28)18 (24)5 (7)29,8360.00253 Disclosures:Off Label Use: Levofloxacin is approved for treatment of infections. We will discuss its use as infection prophylaxis.

Phase II Study of Melphalan, Prednisone and Lenalidomide Combination for Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

Melphalan (M), Prednisone (P) and Lenalidomide (R) are active in the treatment of multiple myeloma (MM). We evaluated the toxicity and efficacy of MPR in a phase I/II trial. Results of phase I part were previously reported (Blood 2006, 108(11) abst 3558). M 5 mg/m2 on days (d) 1–4,60 mg/m2 d 1–4 and R 10 mg d 1–21 of a 28 day cycle was determined as MTD for the phase II study.Methods: Patients with previously untreated MM who were not candidates for stem cell transplantation, age ≥18 yr, ECOG PS 0–3, evaluable or measurable disease, ANC >1500, platelets > 100,000 and creatinine ≤ 3.0 mg/dL were eligible. All patients received aspirin 325 mg/d as DVT prophylaxis. Routine antibacterial prophylaxis was not used. G/GM-CSF was used at the discretion of the treating physician for neutropenia. Response rate (RR), confirmed on two consecutive determinations was the primary end-point. The study had 90% power to detect a RR of at least 45%.Results: Twenty-six patients were accrued between July ‘06 and Feb ‘08. The median age was 74 y (64 – 87y), 17 (65%) were men. Six, 13, 6, 1 (23%, 50%, 23%, and 4%) patients had ECOG PS 0, 1, 2, and 3, respectively. Three (12%), 11 (42%) and 10 (38%) patients were ISS stage 1, 2 and 3. A total of 106 cycles were administered; median 4.5 (1–13). Seventy-seven % patients experienced at least 1 grade 3 or 4 toxicity. Neutropenia (42%/8%) and thrombocytopenia (20%/8%) were the most common grade 3/4 adverse events followed by anemia (16%/0%), fatigue (8%/4%), rash (11%/0%), and hyperglycemia (4%/0%). There were 20 treatment delays in 9 patients, and 18 dose reductions (9 in R, 11 in M and 1 P) occurred in 7 patients, most commonly because of neutropenia or thrombocytopenia. Eleven patients (42%) required G-CSF treatment. Eleven patients are currently receiving treatment; 15 have gone off study (4 completed per protocol, 3 refused, 3 adverse effects, 3 unrelated illnesses, 2 other). Median follow up of survivors is 8 m (0 – 22m). Eighteen (69 %; 95%CI 48–86) patients had a PR or better according to International Myeloma Working Group Uniform Response criteria; 3 (12 %) CR, 5 (19 %) VGPR and 10 (38%) PR. Median number of cycles before achieving a response was 2 (1 – 11). Median Progression Free and Overall Survival is 16.7m (95% CI 11.2–23.0), and 23 m (95% CI: 22 – 23), respectively.Conclusions: MPR combination is feasible with a manageable toxicity profile and has significant activity in the treatment of patients with MM who are not candidates for stem cell transplant, with an overall response rate of 69%, and a CR plus VGPR rate of 31%. Grade 3 or 4 neutropenia and thrombocytopenia was the most common toxicity, seen in up to 50% of patients in this cohort of predominantly elderly patients. Dose reduction in R and/or M was required in 27% patients. No patient developed neuropathy or thromboembolic complications.

Association of MBL2 genotypes wtih infections and outcome after allogeneic stem cell transplantation

7100 Background: Low MBL2 concentration and MBL2 genotype variants have been associated with an increased risk of infection. Our objective was to correlate MBL2 genotypes with specific infections and outcome of HSCT. Methods: 125 non- consecutive, non-selected HSCT were examined. Patients were classified as high or low risk group based on status of underlying disease. Antifungal prophylaxis consisted of fluconazole 400 mg daily. Patients on steroids received mould prophylaxis. There was no routine antibacterial prophylaxis. Microbiologically confirmed infections were recorded. Genotype was determined by PR-Melting Curve Analysis on blood or buccal swab specimens. MBL genotype was classified as wild-type: A/A (MBL-sufficient, MBL-S) or variant-type: A/O, O/O (MBL deficient, MBL- D). Patients were followed for up to 2 years. Analyses of categorical variables were performed using the Fisher exact test and the Log-Rank test for time to event. Results: Seventy-one (58.2%) patients were homozygous for wild-type MBL2 (AA), 43 (35.3%) were heterozygous (A/0) and 8 (6.5%) were homozygous for variant genotypes (OO). MBL-D group had higher incidence of fungal infections (20% vs 7%, p=0.05), and in particular Aspergillosis (12% vs 3%, p=0.05). MBL-D was associated with a trend for higher rates of bacterial infections (63% vs 46%, p=0.10) and total number of bacterial infections (p=0.10). Rates of respiratory and enteric viral infections or CMV were similar in MBL-D and MBL-S groups (41% vs 38%, p=0.9 and 58% vs. 54% p=1.0 respectively). Patients with MBL-D genotype were at a disadvantage in relapse-free (RFS) and overall survival (OS), (p&lt;0.01 and p=.08). This disadvantage was also observed when stratified by disease risk groups. The estimated 2-year relapse-free survival rate was 30% compared to 53% for MBL-D vs. MBL-S patients (p&lt;0.01). Conclusions: 1) Patients with variant MBL genotype (MBL-D) had a trend for increased incidence and number of bacterial infections. 2) MBL-D genotype and graft versus host disease were risk factors for aspergillosis. 3) MBL-D genotype was associated with worse overall survival and relapse free survival post HSCT. These data suggest that MBL-D patients have impaired immune function compared with MBL-S patients and is consistent with animal data. [Table: see text]

Melphalan (M), Prednisone (P) and Lenalidomide (R) Combination (MPR) for Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation.

Lenalidomide is an orally active immunomodulatory drug effective in the treatment of multiple myeloma. We evaluated the toxicity and efficacy of MPR combination in a phase I/II study. Patients with newly diagnosed symptomatic multiple myeloma who were not candidates or refused stem cell transplantation were eligible. Treatment consisted of M and P on days 1 – 4 and R on days 1 – 21 in a 28 day cycle. All patients received aspirin 325 mg a day. Routine antibacterial prophylaxis was not used. Patients were accrued in cohorts of 3 at dose level 0 (M 5mg/m 2/d P 60 mg/m2/d R 10 mg/d) and level 1 (M 8mg/m2/d P 60 mg/m2/d R 10 mg/d). Patients were followed for at least 2 cycles to assess Dose Limiting Toxicity (DLT). G/GM-CSF use was not allowed in the first 2 cycles unless DLT had occurred. DLT was defined as occurrence of at least grade (G) 4 hematologic toxicity, G3 febrile neutropenia, or G 3 non-hematologic toxicity in the first two cycles. Failure to start the next cycle within 7 days of day 1 due to toxicity also constituted DLT.Results: 7 patients have been accrued (4 at dose level 0 {one patient had to be replaced} and 3 at dose level 1). 4 were males. ECOG performance status was 0 or1 (2 and 4 patients). Median age was 74 yrs, range 72 – 85. Between 3 and 10 cycles (median 4) have been administered at the time of this reporting. The following G3 or higher toxicities were encountered and considered at least possibly related to treatment: 2 patients at level 0 had G3 neutropenia. Of the three patients at dose level 1, there was 1 G4 neutropenia, 1 G4 thrombocytopenia, 1 G3 hyperglycemia and 1 G4 vascular access device related thrombosis. Responses were defined by EBMT/IBMTR criteria. 1 had a complete remission (after 3 cycles), 4 had partial remission (at least 50% reduction in monoclonal protein) and 1 had minimal response (after 3 cycles). Due to 3 DLT's in dose level 1, dose level 0 was chosen for phase II of the study.Conclusion: M 5 mg/m2, P 60 mg/m2 and R 10 mg combination is well tolerated and appears effective in patients with multiple myeloma. These results are similar to the experience reported by Palumbo et al ( Blood 2005, 106(11):abst 785) although a stricter definition of DLT was used in our study. Escalation of R dose in combination with M 5 mg/m2, P 60 mg/m2 may be possible and improve responses. Updated data will be presented.

Randomised, placebo-controlled, trial comparing low dose versus standard dose Lenograstim (L) following myeloablative chemotherapy (HDT) and peripheral blood progenitor cell rescue (PBPCR) for lymphoma

7624 Background: This trial was performed to determine whether low-dose or standard dose L would influence recovery of haematopoiesis following HDT and PBPCR. Methods: 61 patients (pts) with non-Hodgkin lymphoma (40) or Hodgkin’s disease (21) undergoing HDT were randomised. Pts had normal peripheral blood counts prior to HDT (Hb ≥100g/L, total white cell count ≥ 3.0, neutrophils (N) ≥ 1.0 and platelets ≥ 50, and had a minimum 2.5 million CD34+ cells/kg PBPC previously collected following mobilisation with Cyclophosphamide 3g/m2 and G-CSF. All received HDT with BCNU 300mg/m2 d-7, Etoposide 200mg/m2 od d-5-d-2, Cytosine arabinoside 200mg/m2 bd d-5-d-2 and Melphalan 140mg/m2 d-1 before return of PBPC on D0. Pts were allocated standard dose L 263mcg daily (20 pts), low dose L 105mcg daily (21 pts) or placebo injections (20 pts). These commenced on day +5 following PBPCR and continued until N≥0.5. Pts received standard supportive care including prophylactic Fluconazole and Acyclovir, but not routine antibacterial prophylaxis, until haemopoietic recovery. Results: L at any dose resulted in a significantly shorter median time to N recovery ≥0.1 (10.0 vs 11.0 days, P=0.02) and ≥0.5 (11.0 vs 14.0 days, p=0.0003) compared to placebo. The only significant difference between standard- and low-dose L was in hospital stay (21.0 vs 22.0 days, p=0.04), however L at any dose showed a significant reduction over placebo (22.0 vs 23.0 days, p=0.01). Conclusions: Short course low dose L is as effective as standard dose in reducing neutrophil engraftment time following HDT and PBSCR. L at any dose reduces hospital stay when compared to placebo. This approach should be considered for those patients in whom growth factor support is indicated. Long-term follow-up data will be presented. [Table: see text] No significant financial relationships to disclose.

Counterpoint: Routine Anti-Bacterial Prophylaxis Is Not Indicated in Neutropenic Patients With Hematological Malignancies

Preventing bacterial infections by prescribing prophylactic antibiotics is seen by many as an important strategy for decreasing infectious mortality in the most profoundly immunosuppressed patients with hematologic malignancies. Comparative studies show consistently that neutropenic patients treated with prophylactic fluoroquinolone antibiotics develop fewer bacteremias than patients treated with placebo or less-potent antibacterials. However, these same studies fail to show increased survival rates in fluoroquinolone-treated patients. This repeated observation is the basis for the continued controversy concerning universal antibacterial prophylaxis of neutropenic patients, namely, the inability to translate the observed reduction in culture-proven bacterial infections with prophylaxis into improved clinical outcomes. The answer to this controversy lies in the effectiveness of empiric antibacterial therapy in response to neutropenic fevers. Mortality from bacterial infections is 1% or less for patients enrolled in empiric treatment trials who do not receive prophylactic antibacterials. Therefore, routine fluoroquinolone prophylaxis offers essentially no potential survival benefit to neutropenic patients with hematologic malignancies. In fact, the increasing potential for fluoroquinolones to select for resistant bacterial pathogens should give pause to the practice of routine prophylaxis of neutropenic patients.

Antimicrobial prophylaxis in febrile neutropenia.

Antibiotics generally considered for antibacterial prophylaxis for immunosuppressed patients are trimethoprim-sulfamethoxazole and the quinolones. Trimethoprim-sulfamethoxazole can significantly reduce infections and is highly effective in preventing pneumonia due to Pneumocystis carinii. However, it can cause sulfonamide-related reactions, myelosuppression, oral candidiasis, and development of bacterial resistance, and it lacks activity against Pseudomonas aeruginosa. Quinolones can reduce the occurrence of fever and infections in patients with neutropenia but do not provide adequate coverage against gram-positive bacteria, and inappropriate use can induce resistance among gram-negative organisms. Routine antibacterial prophylaxis is not recommended for patients likely to develop neutropenia. Antifungal prophylaxis is appropriate in settings in which fungal infections are frequent. Fluconazole is recommended for patients who are to undergo hematopoietic stem cell transplantation; it can be considered for elderly patients with acute leukemia who are to receive intensive chemotherapy. Itraconazole can also be used. Prophylaxis with antiviral agents is generally not indicated; however, it should be given to hematopoietic stem cell transplant recipients.

Intraabdominal sepsis: newer interventional and antimicrobial therapies for infected necrotizing pancreatitis.

Recent advances in interventional techniques and antimicrobial therapy have significantly affected the morbidity and mortality of infected pancreatic necrosis. This review describes elements of this progress. Operative management of infected pancreatic necrosis has consisted of formal laparotomy and debridement of the pancreatic necrosis/infection. Typically, the abdominal wound has been left open and the pancreatic bed has been reexplored at frequent intervals. This staged approach has been replaced by a single definitive operative procedure. More recently, laparoscopic techniques have been used, and provide the possibility of substantially lessened morbidity. The benefits of antimicrobial prophylaxis, typically with carbapenems, have been demonstrated in several clinical trials. The use of such broad-spectrum therapy has complicated the antimicrobial management of prophylaxis failures. A resistant flora is encountered in such patients, including gram-positive cocci, yeast, and gram-negative bacilli. This has been shown to mandate empiric therapy with combination regimens based on agents not used for prophylaxis. These findings recommend the practice of routine antibacterial prophylaxis with systemic agents. Patients receiving such treatment should be monitored for colonization by yeast; surveillance cultures do not appear to be necessary because these critically ill patients have an inflammatory disease and frequently experience temperature elevations warranting cultures to rule out infection. If infection is documented by aspiration or intervention, aggressive antimicrobial therapy directed at organisms identified by Gram stain should be started. Classes of antimicrobial agents other than those used for prophylaxis should be used.

Trimethoprim versus Gentamicin for the Prevention of Bacteriuria following Transrectal Biopsy of the Prostate – Do Patients Need Additional Anaerobic Cover?

Objectives: To study the incidence of aerobic and anaerobic bacteriuria in patients undergoing transrectal ultrasound-guided biopsies of the prostate. A comparative assessment of efficacy of trimethoprim with gentamicin for the prevention of bacteriuria following the transrectal biopsy of the prostate. To assess the need for additional prophylaxis against anaerobes for patients undergoing transrectal biopsies of the prostate gland. Patients and Methods: In a pilot study during 1995–1997, all the patients undergoing transrectal ultrasound-guided biopsy of the prostate were randomised to receive either trimethoprim or gentamicin prophylaxis prior to the procedure. Midstream urine (MSU) samples were taken just prior to biopsy and 72 h later. A patient questionnaire to determine the symptoms of urinary tract infection (UTI) accompanied the 72-hour MSU request form. Urine samples were cultured aerobically, using a semiquantitative technique if dipstick analysis revealed the presence of blood, pus cell or nitrite. In addition to the routine aerobic culture, post-biopsy samples were also cultured for anaerobes by direct and enrichment methods. Bacteriuria was defined as a pure or mixed growth of 10⁵ colony-forming units/ml. Fisher’s test of exact probability was used for statistical analysis. Results: 115 patients were available for final analysis. 53 had received gentamicin and 62 trimethoprim. Four patients had pre-existing bacteriuria (3.5%), 3 in the trimethoprim group and 1 in the gentamicin group. Post-operative bacteriuria developed in 5 patients given gentamicin (9.4%) and 1 given trimethoprim (1.6%). This difference was not statistically significant (p = 0.085). Post-procedure bacteriuria was asymptomatic in all but 1 case. Anaerobes were detected in only 5 MSUs (4.3%) post-biopsy. Conclusion: Though there was no statistical significant difference in the rates of bacteriuria following administration of trimethoprim and gentamicin, data appear to favour trimethoprim prophylaxis. Further studies are warranted. Transrectal biopsy of the prostate is associated with a low incidence of anaerobic UTI. In view of the very low incidence of anaerobic bacteriuria, routine antibacterial prophylaxis against anaerobes does not appear to be justified.