Percutaneous nephrostomy catheter-related infections in patients with gynaecological cancers: a multidisciplinary algorithmic approach.

BACKGROUND: Percutaneous nephrostomy catheters (PCNs) are commonly utilized in patients with gynaecological cancers due to intrinsic or extrinsic urinary obstruction. Unfortunately, these foreign medical devices may be associated with several infectious complications, including: pyelonephritis, renal abscess, and bacteraemia, which may lead to further delay of life-saving cancer therapy. AIM: To evaluate the performance of our multidisciplinary algorithm for diagnosis and treatment of PCN-related infections (PCNIs) and identify risk factors for recurrent urinary device-related infections. METHODS: Patients with gynaecological cancers having PCNIs were prospectively evaluated at our institution from July 2019 to September 2021. All patients were managed by our standardized algorithm and followed-up until reinfection or routine PCN exchange. FINDINGS: Of 100 consecutive patients with PCNIs, 74 had adequate follow-up, and were analysed in three groups according to clinical outcome: reinfection with the same organism (26%), reinfection with a different organism (23%), and no reinfection (51%). Their median age was 54 years, and the most common cancers were cervical (65%), and ovarian (19%) with 53% being metastatic. The most frequently recovered micro-organisms were Pseudomonas (32%), Enterococcus (27%), and Escherichia (24%) species. The main risk factors for recurrent PCNI with the same organism were pelvic radiation therapy (P=0.032), pelvic fistulas (P=0.014), and a PCNI with the same pathogen within the previous year (P = 0.012). CONCLUSIONS: Our algorithm has allowed for accurate diagnosis, staging, and treatment of and identification of several key risk factors for recurrent PCNIs. These results may lead to further preventive measures for these infections.

Invasive pulmonary aspergillosis: comparative analysis in cancer patients with underlying haematologic malignancies versus solid tumours.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is commonly associated with haematologic malignancies but also occurs with solid tumours. AIM: To compare the diagnostic approaches and therapeutic outcomes for IPA between patients with haematologic malignancies and solid cancers. METHODS: A retrospective study was conducted evaluating consecutive cases of proven and probable IPA from 2004 to 2016. Patients >18 years of age with an underlying solid tumour, haematologic malignancy, or haematopoietic cell transplantation (HCT) within one year of IPA diagnosis were included. FINDINGS: Of the 311 patients analysed, 225 had haematologic malignancies and 86 had solid tumours. Patients with solid tumours were more likely to have had chronic obstructive pulmonary disease (COPD) or other pulmonary diseases, have Aspergillus fumigatus infections, and have received radiotherapy before IPA occurrence than were those with haematologic malignancies (all P<0.01). Antifungal monotherapy and voriconazole-based therapy were more often prescribed in the solid group (87% vs 56%, P<0.0001, and 77% vs 53%, P=0.0002, respectively). The median duration of primary antifungal therapy was longer in the solid group (64 days vs 20 days, P<0.0001). Complete or partial response to antifungal therapy was recorded in 66% of the solid group and 40% of the haematologic group (P=0.0001). At 12 weeks, overall mortality was similar in both groups, but IPA-attributable mortality was higher in the haematologic group (30% vs 18%, P=0.04). CONCLUSIONS: Monotherapy was more often prescribed in patients with solid tumours than in patients with haematologic malignancies. Patients with solid tumours had better antifungal therapy response and lower 12-week IPA-attributable mortality than did those with haematologic malignancies.

Whole-genome sequencing of Staphylococcus epidermidis bloodstream isolates from a prospective clinical trial reveals that complicated bacteraemia is caused by a limited number of closely related sequence types.

OBJECTIVES: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia. METHODS: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information. RESULTS: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001). CONCLUSION: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections.

Glyceryl trinitrate and caprylic acid for the mitigation of the Desulfovibrio vulgaris biofilm on C1018 carbon steel.

Microbiologically influenced corrosion (MIC), also known as biocorrosion, is caused by corrosive biofilms. MIC is a growing problem, especially in the oil and gas industry. Among various corrosive microbes, sulfate reducing bacteria (SRB) are often the leading culprit. Biofilm mitigation is the key to MIC mitigation. Biocide applications against biofilms promote resistance over time. Thus, it is imperative to develop new biodegradable and cost-effective biocides for large-scale field applications. Using the corrosive Desulfovibrio vulgaris (an SRB) biofilm as a model biofilm, this work demonstrated that a cocktail of glyceryl trinitrate (GTN) and caprylic acid (CA) was very effective for biofilm prevention and mitigation of established biofilms on C1018 carbon steel coupons. The most probable number sessile cell count data and confocal laser scanning microscope biofilm images proved that the biocide cocktail of 25 ppm (w/w) GTN + 0.1% (w/w) CA successfully prevented the D. vulgaris biofilm establishment on C1018 carbon steel coupons while 100 ppm GTN + 0.1% CA effectively mitigated pre-established D. vulgaris biofilms on C1018 carbon steel coupons. In both cases, the cocktails were able to reduce the sessile cell count from 10(6) cells/cm(2) to an undetectable level.

Granulocyte transfusions in hematologic malignancy patients with invasive pulmonary aspergillosis: outcomes and complications.

BACKGROUND: Granulocyte transfusions (GTXs) have been used successfully as an adjunctive treatment option for invasive infections in some neutropenic patients with underlying hematologic malignancy (HM). PATIENTS AND METHODS: We sought to determine the impact of GTX as an adjunct to antifungal therapy in 128 patients with HM and prolonged neutropenia (≥14 days) with a proven or probable invasive aspergillosis (IA) infection by retrospectively reviewing our institutional database. RESULTS: Fifty-three patients received GTX and 75 did not. By univariate analysis, patients with invasive pulmonary aspergillosis who received GTX were less likely to respond to antifungal therapy (P = 0.03), and more likely to die of IA (P = 0.009) when compared with the non-GTX group. Among patients who received GTX, 53% developed a pulmonary reaction. Furthermore, IA-related death was associated with the number of GTX given (P = 0.018) and the early initiation of GTX within 7 days after starting antifungal therapy (P = 0.001). By multivariate competing risk analysis, patients who received GTX were more likely to die of IA than patients who did not receive GTX (P = 0.011). CONCLUSIONS: Our study suggests that GTX does not improve response to antifungal therapy and is associated with worse outcomes of IA infection in HM patients, particularly those with pulmonary involvement.

Chelator-based catheter lock solutions in eradicating organisms in biofilm.

Two different chelator-based antimicrobial catheter lock solutions, methylene blue-citrate-parabens (MB-CIT) and minocycline-EDTA-25% ethanol (M-EDTA-25% ETOH), were compared in 2-h biofilm eradication experiments. Eradication of both mature and immature Gram-positive, Gram-negative, and fungal biofilms was assessed. M-EDTA-25% ETOH was able to fully eradicate all biofilms within 2 h. MB-CIT was only effective against immature biofilms but was unable to fully eradicate most of the mature biofilms tested.

D-amino acids for the enhancement of a binary biocide cocktail consisting of THPS and EDDS against an SRB biofilm.

Biofilms of sulfate reducing bacteria (SRB) are often responsible for Microbiologically Influenced Corrosion (MIC) that is a major problem in the oil and gas industry as well as water utilities and other industries. This work was inspired by recent reports that some D: -amino acids may be useful in the control of microbial biofilms. A D: -amino acid mixture with equimolar D: -tyrosine, D: -methionine, D: -tryptophan and D: -leucine was tested in this work for their enhancement of a biocide cocktail containing tetrakis (hydroxymethyl) phosphonium sulfate (THPS) and ethylenediamine-N,N'-disuccinic acid (EDDS). Desulfovibrio vulgaris (ATCC 7757) was cultured in ATCC 1249 medium. Its biofilm was grown on C1018 carbon steel coupons. Experimental results indicated that the triple biocide cocktail consisting of 30 ppm THPS, 500 ppm EDDS and 6.6 ppm D: -amino acid mixture (with equimolar D: -tyrosine, D: -methionine, D: -tryptophan and D: -leucine) was far more effective than THPS and EDDS alone and their binary combination. The triple biocide cocktail effectively prevented SRB biofilm establishment and removed the established SRB biofilm. The D: -amino acid mixture alone did not show significant effects in the two tasks even at 660 ppm.

A green triple biocide cocktail consisting of a biocide, EDDS and methanol for the mitigation of planktonic and sessile sulfate-reducing bacteria.

Sulfate-reducing bacteria (SRB) cause souring and their biofilms are often the culprit in Microbiologically Influenced Corrosion (MIC). The two most common green biocides for SRB treatment are tetrakis-hydroxymethylphosphonium sulfate (THPS) and glutaraldehyde. It is unlikely that there will be another equally effective green biocide in the market any time soon. This means more effective biocide treatment probably will rely on biocide cocktails. In this work a triple biocide cocktail consisting of glutaraldehyde or THPS, ethylenediaminedisuccinate (EDDS) and methanol was used to treat planktonic SRB and to remove established SRB biofilms. Desulfovibrio vulgaris (ATCC 7757), a corrosive SRB was used as an example in the tests. Laboratory results indicated that with the addition of 10-15% (v/v) methanol to the glutaraldehyde and EDDS double combination, mitigation of planktonic SRB growth in ATCC 1249 medium and a diluted medium turned from inhibition to a kill effect while the chelator dosage was cut from 2,000 to 1,000 ppm. Biofilm removal was achieved when 50 ppm glutaraldehyde combined with 15% methanol and 1,000 ppm EDDS was used. THPS showed similar effects when it was used to replace glutaraldehyde in the triple biocide cocktail to treat planktonic SRB.

Predictors of catheter-related gram-negative bacilli bacteraemia among cancer patients.

Gram-negative bacillary bacteraemia (GNB) is associated with high morbidity and mortality among cancer patients. We conducted this study to determine the risk factors that may predict the catheter as the source of GNB in cancer patients. From July 2005 to December 2006 all 266 cancer patients with GNB and central venous catheters (CVCs) at The University of Texas M. D. Anderson Cancer Centre in Houston, were classified as catheter-related bloodstream infection (CRBSI) according to Infectious Diseases Society of America criteria. We compared clinical and microbiological features of CRBSIs and non-CRBSIs. We identified 78 CRBSIs and 126 non-CRBSIs. On univariate analysis, polymicrobial bacteraemia, Stenotrophomonas maltophilia bacteraemia, and more than 1000 CFUs in CVC blood cultures, were more common among CRBSI cases. Escherichia coli bacteraemia, haematologic cancer, neutropenia and prior antibiotic use were more common among non-CRBSI cases. On multivariate analysis, S. maltophilia bacteraemia (odds ratio (OR), 5.78; 95% confidence interval (CI), 1.47-22.78; p 0.045), polymicrobial bacteraemia (OR, 4.04; 95% CI, 1.56-10.44; p 0.042), and more than 1000 CFUs from CVC blood cultures (OR, 4.39; 95% CI, 2.02-9.27; p <0.01), were associated with CRBSI. Neutropenia was associated with non-CRBSI (OR, 0.26; 95% CI, 0.13-0.53; p <0.01). Several factors such as S. maltophilia bacteraemia, polymicrobial bacteraemia and more than 1000 CFUs from a blood culture drawn through the CVC may assist the clinicians in assessing whether an indwelling catheter is the source of a GNB and hence CVC removal may be considered.

Comparing clinical and microbiological methods for the diagnosis of true bacteraemia among patients with multiple blood cultures positive for coagulase-negative staphylococci.

We assessed the accuracy of the Centers for Disease Control and Prevention (CDC) clinical criteria as well as other microbiological methods for the diagnosis of coagulase-negative staphylococci bacteraemia. The CDC clinical criteria had low accuracy, which can be improved by speciation, particularly if the patient had more than two positive blood cultures.

Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort.

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.

The efficacy of catheters coated with minocycline and rifampin in the prevention of catheter-related bacteremia in cancer patients receiving high-dose interleukin-2.

High-dose interleukin-2 (HDIL-2) has proven to be an effective treatment for metastatic renal cell carcinoma and melanoma. Previous studies have shown an increase in catheter-related bacteremia (CRB) in patients on HDIL-2. The primary objective of this study was to evaluate the effectiveness of minocycline and rifampin-coated catheters (M/R-C) in reducing CRB in cancer patients on HDIL-2. This was a retrospective study where non-coated catheters (NC-C) and M/R-C were used for the administration of HDIL-2 before and after December 2004, respectively. Data collected included demographics, cancer type, catheter type, antibiotic prophylaxis, and infection rates. A total of 107 episodes of catheter use for HDIL-2 were evaluated in 78 patients (30 episodes in patients with M/R-C vs. 77 with NC-C). A total of nine episodes of CRB were identified, all in patients with NC-C (M/R-C 0% vs. NC-C 12%; p=0.06). The median time to bacteremia was 11 days (range 1-315 days). A log-rank test showed a trend that the M/R-C group had lower probability of getting CRB than the NC-C group (p=0.06). The use of M/R-C in patients on HDIL-2 therapy for advanced melanoma and renal cell carcinoma may have reduced the risk of CRB to nil. CRB still occurred despite antibiotic prophylaxis in patients with NC-C.

Catheter-related Corynebacterium bacteremia: should the catheter be removed and vancomycin administered?

The purpose of this study was to determine the need for central venous catheter removal in patients with corynebacterial catheter-related bloodstream infections and the impact of central venous catheter retention on response to systemic antibiotic therapy and relapse. We searched the microbiology laboratory database and patients' medical records at our institution between January 2000 and December 2006. We identified 98 patients with corynebacteria infection. Most of the episodes (94%) were catheter-related. Removing the catheter did not affect the outcome of treatment, particularly when an active non-glycopeptide antibiotic was used. All Corynebacterium species isolates were susceptible to vancomycin, 54/55 (98%) to linezolid, 80/95 (84%) to rifampin, and 69/85 (81%) to tetracycline. The median duration of antibiotic therapy was 12 days (range, 0-28), and vancomycin was the most commonly used antibiotic (64%). There was a trend toward earlier fever resolution in patients treated with non-glycopeptide antibiotics compared to vancomycin, particularly if the catheter was not removed. Central venous catheter removal might not be necessary in patients with corynebacterial catheter related bloodstream infection, particularly if systemic therapy consists of non-glycopeptide antibiotics. Treatment with a systemic active antibiotic over a 7-day period appears to be adequate for resolution of the infection.

Utility of galactomannan enzyme immunoassay and (1,3) beta-D-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients.

Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in hematologic malignancy patients.

Severe parainfluenza virus type 2 supraglottitis in an immunocompetent adult host: an unusual cause of a paramyxoviridae viral infection.

Parainfluenza virus is a major cause of respiratory illness in humans, manifesting from mild upper respiratory tract infection to bronchiolitis and pneumonia, especially in children. We report - to our knowledge - the first case of a nonimmunocompromised adult patient with human parainfluenza type 2 supraglottitis immediately after returning from China.

Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance.

We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13% vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled antibiotics developed nephrotoxicity (P < or = 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious toxicity and may lead to improved outcome.

Fatal cytomegalovirus pneumonia in patients with haematological malignancies: an autopsy-based case-control study.

Cytomegalovirus (CMV) pneumonia is a life-threatening infection in patients with haematological malignancies (HMs) or in haematopoietic stem cell transplant (HSCT) recipients. To assess the incidence and risk factors for developing fatal CMV pneumonia in these patients, a case-control study based on 999 autopsies was performed at The University of Texas M. D. Anderson Cancer Center, Houston, Texas (January 1990 to December 2004). Twenty-five cases (patients who died with CMV pneumonia) were matched with 34 controls (patients who died without CMV pneumonia) by type of HM or HSCT, year of autopsy, age and gender. The incidence of CMV pneumonia declined between January 1990 to June /1997 and July 1997 to December 2004 (CMV pneumonia rates were 22/620 and 3/379 autopsies, respectively; p 0.006). Logistic regression analysis identified complete remission and sustained lymphopenia as independent predictors of CMV pneumonia (all p <0.05). The incidence of fatal CMV pneumonia has decreased over the last 15 years, which might reflect earlier diagnosis or the use of pre-emptive therapy or more effective preventive strategies. Complete remission of an HM does not preclude the development of CMV pneumonia among patients with prolonged lymphopenia.

Posaconazole as salvage treatment of invasive fungal infections in patients with underlying renal impairment.

OBJECTIVES: The aim of this study is to determine the efficacy and safety of posaconazole in patients with underlying renal impairment. Patients and methods We analysed the efficacy and safety of posaconazole in patients with renal impairment in a post hoc subanalysis of a Phase 3, multicentre, open-label trial in patients with invasive fungal infections (IFIs). In the Phase 3 study, 330 patients intolerant of or with IFIs refractory to standard antifungal therapy received posaconazole 800 mg daily in divided doses. In our subanalysis, 238 patients with proven/probable IFIs, including 65 patients with renal impairment (creatinine clearance < 50 mL/min or serum creatinine (sCR) level >2 mg/dL at baseline) and 173 patients with greater renal function [creatinine clearance >/= 50 mL/min (acceptable renal function)], formed the modified intent-to-treat population. Success was defined as complete or partial response, and non-success was defined as stable disease or treatment failure. RESULTS: Overall response rates were similar in the renal impairment group (49%) and in the acceptable renal function (50%) group. Seventeen of the 41 patients with renal impairment and aspergillosis responded. Adverse events occurred in 32/65 (49%) patients with renal impairment and in 72/173 (42%) patients with acceptable renal function. The most common adverse events in both groups were nausea (14% patients with renal impairment versus 8% with acceptable renal function), altered/elevated levels of other medications (8% versus 2%), increased sCR levels (6% versus 0%), vomiting (6% versus 4%), abdominal pain (5% versus 5%) and dizziness (5% versus 1%). CONCLUSIONS: These results suggest that posaconazole is effective and well tolerated in patients with refractory IFIs regardless of renal impairment.