Clinical Outcomes of Trimethoprim/Sulfamethoxazole in Critically Ill Patients with Stenotrophomonas maltophilia Bacteremia and Pneumonia Utilizing Renal Replacement Therapies.

Background: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating S. maltophilia in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. Methods: A retrospective study was performed on all critically ill adult patients with S. maltophilia infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. Results: Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m2. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group (p = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group (p = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group (p = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), p = 0.044]. Conclusions: Although the S. maltophilia isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.

Microbiologic outcomes of ceftazidime-avibactam dosing in patients with sepsis utilizing renal replacement therapies.

INTRODUCTION: The suggested dose of ceftazidime-avibactam (CEF/AVI) in patient with multidrug resistant organisms and utilizing renal replacement therapies (RRTs) is not validated in clinical studies. The objective of this study was to evaluate the microbiologic cure of bacteremia and pneumonia using the recommended CEF/AVI dosing in patients utilizing RRT. METHODS: A retrospective observational study conducted at our institution between September 15, 2018 and March 15, 2022. The primary end point was to determine the microbiologic cure. The secondary end points were the clinical cure, 30-day recurrence, 30-day all cause mortality. RESULTS: Fifty-six patients met the inclusion criteria, 36 (64.3%) were males, the median age was 69 (59.5-79.3) years, and the median weight was 69 (60-83.8) kg. Pneumonia represented 34 (60.7%) of infections. Microbiologic cure was achieved in 32 (57%) subjects. However, clinical cure was achieved in 23 (71.9%) patients in the microbiologic cure group versus 12 (50%) in the microbiologic failure group (p = 0.094). The 30-day recurrence occurred in 2 (6.3%) patients in the microbiologic cure group versus 3 (12.5%) in the microbiologic failure group (p = 0.673). Further, the 30-day all-cause mortality was 18 (56.3%) versus 10 (41.7%) in both groups respectively (p = 0.28). The most used dose in patients utilizing continuous veno-venous hemofiltration (CVVH) was 1.25 g q8h, while the dose was 1.25 g q24h in those who utilized intermittent hemodialysis (IHD). The multivariate logistic regression indicated that bacteremia (OR 41.5 [3.77-46]), Enterobacterales (OR 5.4 [1.04-27.9]), and the drug daily dose (OR 2.33 [1.15-4.72]) were independently associated with microbiologic cure. CONCLUSION: Microbiologic cure of ceftazidime-avibactam in patient utilizing CVVH and IHD is dependent on bacteremia diagnosis, the drug daily dose, and bacterial species. These findings need to be replicated in a larger prospective study, with no recommendations in those utilizing RRT.

Urinary tract infections in hemodialysis patients-The controversy of antimicrobial drug urine concentrations.

BACKGROUND: Major infectious diseases societies recommend the use of antimicrobials that achieve high-urinary concentrations to treat urinary tract infection (UTI), which is a concept of little relevance to the oliguric and anuric hemodialysis (HD) dependent population. Outcome studies in this population are more relevant, but unfortunately scarce. We sought to investigate the impact of different antimicrobials on clinical and microbiologic outcomes in HD dependent population. METHODS: A retrospective observational study conducted at our quaternary care hospital between May 2015 and December 2019. We included all HD dependent adults diagnosed with UTIs. Our primary end points were clinical and microbiologic cure. Our secondary end points were 90-day recurrence and mortality. RESULTS: Fifty-six patients were included in the study with 33 (58.9%) females, mean age of 69.9 ± 11.6 years, and mean body mass index of 27.7 ± 7.8 kg/m2 . Thirty-six subjects of the sample (64.3%) were anuric. Ninety-one percent of the patients achieved clinical cure. Out of those who had repeat cultures, 90.7% achieved microbiologic cure. Clinical and microbiologic cure rates were not significantly different between the oliguric and anuric groups. The 90-day recurrence rate was 11.1% and mortality was 19%, none of them was related to UTI. CONCLUSION: Our findings demonstrate high rate of clinical and microbiologic cure in the treatment of oliguric and anuric HD dependent patients. We suggest that drug development and treatment societies to consider clinical and microbiologic outcomes in conjunction with achievable urinary concentration when making recommendations for the treatment of UTI.

Nocardial Infection in the Early Period after Kidney Transplantation.

Patients with solid organ transplant have weaker immune system and can develop opportunistic infections. Prophylactic antimicrobials can help lower that risk but do not prevent it completely. High index of suspicion increases the chance of diagnosing rare opportunistic infections in immunocompromised patients and helps early and effective treatment. We present a unique case of a patient who developed pneumonia from Nocardia early after kidney transplant despite being on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. He was diagnosed and treated early which helped improving his outcome. We discuss incidence, risk factors, and treatment of nocardiosis post kidney transplant.

Outcomes of caspofungin use in the treatment of Candida-related urinary tract infections, a case series.

Echinocandins are generally excluded in the treatment of Candida-related urinary tract infections due to their poor urinary concentration. In the presence of fluconazole resistant Candida species, such as C. Glabrata and C. auris, alternative therapies are needed. We herein report the use of caspofungin for the treatment of 10 patients with candiduria, including C. auris. Mycological cure was achieved in 6 of 7 patients and clinical cure was achieved in 8 of 10 patients. Larger studies are needed to confirm our findings.

Multiple concomitant life-threatening opportunistic infections due to uncontrolled hypercortisolism.

Opportunistic infections associated with severe cortisol excess carry a high mortality rate and are most prevalent with ectopic ACTH syndrome. There are limited reports of these cases described in the literature. In this case report, we describe multiple severe life-threatening opportunistic infections due to endogenous hypercortisolism. Our patient, against numerous expectations, survived multiple opportunistic infections including disseminated invasive aspergillosis, Cytomegalovirus endophthalmitis and Pneumocystis Jirovecii pneumonia, reinforcing the need for multidisciplinary care for patients presenting with complicated hypercortisolism.

Varicella-Zoster Meningitis in an Immunocompetent Male without Fever or Rash.

Varicella-Zoster virus (VZV) is a human herpesvirus that primarily causes chickenpox and can reactivate later in life. Chickenpox occurs mostly in children and is characterized by a typical generalized vesicular rash. Following the primary infection, VZV can remain latent and can reactivate decades later to produce Zoster, being more common in the elderly as well as immunosuppressed individuals. The diagnosis of both the primary and reactivation is mostly clinical from the typical rash. However, when presentations are atypical, it leads to diagnostic challenges. We report an unusual case of VZ reactivation in an immunocompetent young adult presenting without fever, zoster rash, or neuralgia. The diagnosis was established by a positive polymerase chain reaction (PCR) performed on cerebrospinal fluid samples. The patient was treated with acyclovir and responded very well. The diagnosis of VZ meningitis is challenging in the absence of typical features of Zoster rash and requires a high index of suspicion.

Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease.

ABSTRACT: There are conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients. The objective of this study was to assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance.Hospitalized adult patients with confirmed SARS-CoV-2 infection were retrospectively included in the study. The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by 2 negative results using RT-PCR assay with samples obtained 24 hours apart. Multiple linear regression analysis was used to adjust for potential confounders.Thirty-four confirmed COVID-19 patients completed the study. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ than those who did not receive HCQ [17 (13-21) vs 10 (4-13) days, P = .023]. HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, comorbidities, antiviral drugs, pneumonia, or oxygen therapy) in multivariable Cox proportional hazards regression analysis (hazard ratio = 0.33, 95% confidence interval: 0.13-0.9, P = .024). On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared with 90.9% (10/11) patients who did not receive HCQ (P = .016).HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.

Treatment of severe pneumonia due to COVID-19 with peginterferon alfa 2a.

The outbreak of the new coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. Until now, no definite effective treatment has been identified. We reported 3 patients with severe COVID-19 treated with pegylated interferon alfa 2a with satisfactory recovery. Based on these observations, randomized studies with interferons should be considered in deteriorating patients infected with COVID-19.

Treatment of recurrent urinary tract infections in anuric hemodialysis patient, do we really need antimicrobial urinary concentration?

Providing care for patients with chronic kidney disease requires considerations that are unique to this population. Several references recommend the treating urinary tract infections with antibiotics that achieve considerable concentrations in urine however this is not applicable in anuric patients undergoing hemodialysis who are unable to excrete antibiotics significantly in urine. We report successful treatment of several episodes of urinary tract infections in hemodialysis patient highlighting the questionable need for antimicrobial urine concentration.

Emergence of KPC-possessing Klebsiella pneumoniae in Brooklyn, New York: epidemiology and recommendations for detection.

Among 257 isolates of Klebsiella pneumoniae collected in Brooklyn, NY, 24% were found to possess bla(KPC). Clinical microbiology laboratories that used automated broth microdilution systems reported 15% of the KPC-possessing isolates as susceptible to imipenem. The imipenem MIC was found to be markedly affected by the inoculum. For accurate detection of KPC-possessing K. pneumoniae, particular attention should be paid to proper inoculum preparation for broth-based susceptibility methods. In addition, using ertapenem or meropenem for class reporting of carbapenem susceptibility will improve detection.

Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents.

OBJECTIVES: To describe the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Brooklyn, NY and assess the in vitro activity of various antibiotic combinations. METHODS: Clinical isolates with suspected carbapenem resistance were referred to the central research laboratory from August 2003 to June 2004. Isolates underwent MIC testing, ribotyping, and were analysed for the presence of KPC carbapenemases. Time-kill studies using various antibiotic(s) were performed on selected isolates. RESULTS: Ninety-six isolates were referred from 10 Brooklyn hospitals. All isolates were resistant to the carbapenems with most having MICs >32 mg/L. Few were susceptible to fluoroquinolones and cephalosporins; approximately half were susceptible to aminoglycosides, and 90% to polymyxin B. Two-thirds were susceptible to doxycycline, and all were considered susceptible to the investigational glycylcycline antibiotic tigecycline. Virtually all possessed bla(KPC), and over 80% belonged to one ribotype. In time-kill studies involving 16 isolates, tigecycline demonstrated bacteriostatic activity and polymyxin B concentration-dependent bactericidal activity. The combination of polymyxin B at 0.5 x MIC plus rifampicin had synergic activity against 15/16 isolates, including two polymyxin-resistant strains. The combination of polymyxin B plus imipenem had synergic bactericidal activity against 10/16 isolates, but was antagonistic for three isolates. CONCLUSIONS: Multiresistant K. pneumoniae with bla(KPC) are present in multiple hospitals in New York City. The most consistently active agents in vitro were tigecycline and polymyxin B, particularly when the latter was combined with rifampicin. The clinical efficacy of these agents remains to be determined.