Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections Due to Extended-Spectrum Beta-Lactamase (ESBL)-Producing Klebsiella pneumoniae.

BACKGROUND Carbapenems are the primary treatment for urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae. However, the recurrence rate is high, and patients often require rehospitalization. We present the results of an observational study on patients with recurrent UTIs who were treated in an outpatient setting with maximal therapeutic oral doses of amoxicillin with clavulanic acid. MATERIAL AND METHODS All patients had pyuria and ESBL-producing K. pneumoniae in urine culture. The starting dosage was 2875 g of amoxicillin twice daily and 125 mg of clavulanic acid twice daily. We down-titrated the doses every 7-14 days and continued prophylactic therapy with amoxicillin/clavulanic acid at 250/125 mg for up to 3 months. We defined therapeutic failure as ESBL-positive K. pneumoniae in urine culture during therapy and recurrence as positive urine culture with the same strain within 1 month after the end of treatment. RESULTS We included 9 patients: 7 kidney graft recipients, 1 liver graft recipient, and 1 patient with chronic kidney disease. We observed no therapeutic failures and no recurrences in the study group during the study period. In 1 case, the patient experienced a subsequent UTI caused by ESBL-producing K. pneumoniae 4 months after completing the therapy. CONCLUSIONS In conclusion, it is possible to break the resistance of ESBL-producing K. pneumoniae strains with high doses of oral amoxicillin with clavulanic acid. Such treatment could be an alternative to carbapenems in select cases.

Treatment of Donor-derived Carbapenem-resistant Klebsiella pneumoniae Infection after Renal Transplantation with Tigecycline and Extended-infusion Meropenem.

OBJECTIVE: Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation. METHODS: From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed. RESULTS: Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients. CONCLUSION: It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

A Dutch Case Report of Successful Treatment of Chronic Relapsing Urinary Tract Infection with Bacteriophages in a Renal Transplant Patient.

We report a case of a 58-year-old renal transplant patient who developed a recurrent urinary tract infection with an extended-spectrum ß-lactamase (ESBL)-positive Klebsiella pneumoniae strain in the first month posttransplant. Even though it tested susceptible to carbapenems and despite repeated meropenem treatment, his infection recurred. The infection eventually evolved into epididymitis that was successfully treated with meropenem and bacteriophages. This case demonstrates the difficulty of treating relapsing ESBL-positive Gram-negative infections in renal transplant patients.

Childhood urinary tract infection caused by extended-spectrum ß-lactamase-producing bacteria: Risk factors and empiric therapy.

BACKGROUND: This study investigated risk factors of childhood urinary tract infection (UTI) associated with extended-spectrum ß-lactamase (ESBL)-producing bacteria (ESBL-positive UTI) and evaluated antimicrobial resistance as well as empiric treatment of childhood UTI. METHODS: The records of children with positive urine culture between 1 January 2008 and 31 December 2012 were evaluated. Patients with positive urine culture for ESBL-producing bacteria were defined as the ESBL-positive group, whereas patients of the same gender and similar age with positive urine culture for non-ESBL-producing bacteria were defined as the ESBL-negative group. Each ESBL-positive patient was matched with two ESBL-negative patients. RESULTS: The ESBL-positive and negative groups consisted of 154 and 308 patients, respectively. Potential risk factors for ESBL-positive UTI were identified as presence of underlying disease, clean intermittent catheterization (CIC), hospitalization, use of any antibiotic and history of infection in the last 3 months (P < 0.05). On logistic regression analysis, CIC, hospitalization and history of infection in the last 3 months were identified as independent risk factors. In the present study, 324 of 462 patients had empiric therapy. Empiric therapy was inappropriate in 90.3% of the ESBL-positive group and in 4.5% of the ESBL-negative group. Resistance to nitrofurantoin was similar between groups (5.1% vs 1.2%, P = 0.072); resistance to amikacin was low in the ESBL-positive group (2.6%) and there was no resistance in the ESBL-negative group. CONCLUSIONS: Clean intermittent catheterization, hospitalization and history of infection in the last 3 months should be considered as risk factors for ESBL-positive UTI. The combination of ampicillin plus amikacin should be taken into consideration for empiric therapy in patients with acute pyelonephritis who have the risk factors for ESBL-positive UTI. Nitrofurantoin seems to be a logical choice for the empiric therapy of cystitis.

Successful treatment of a disseminated infection with extensively drug-resistant Klebsiella pneumoniae in a liver transplant recipient with a fosfomycin-based multidrug regimen.

Donor-derived infections with multidrug-resistant gram-negative bacteria are associated with poor outcomes, in part because of limited treatment options. Here, we describe a case of donor-derived, disseminated infection with colistin-resistant, carbapenemase-producing Klebsiella pneumoniae in a liver transplant recipient that was cured with addition of intravenous fosfomycin to a multidrug regimen, in conjunction with aggressive surgical source control. Intravenous fosfomycin represents a promising adjunctive agent for use in treatment of extensively drug-resistant infections in immunocompromised hosts.

Carbapenem-resistant Klebsiella pneumoniae urinary tract infection following solid organ transplantation.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging pathogen with a devastating impact on organ transplant recipients (OTRs). Data describing urinary tract infections (UTIs) due to CRKP, compared to extended-spectrum ß-lactamase (ESBL)-producing and susceptible K. pneumoniae, are lacking. We conducted a retrospective cohort study comparing OTRs with a first episode of UTI due to CRKP, ESBL-producing K. pneumoniae, or susceptible K. pneumoniae. We identified 108 individuals; 22 (20%) had UTIs due to CRKP, 22 (20%) due to ESBL-producing K. pneumoniae, and 64 (60%) due to susceptible K. pneumoniae. Compared to susceptible K. pneumoniae (27%), patients with UTIs due to CRKP or ESBL-producing K. pneumoniae were more likely to have a ≥ 24-hour stay in the intensive care unit (ICU) before or after development of the UTI (64% and 77%, respectively; P < 0.001). Among 105/108 hospitalized patients (97%), the median lengths of stay prior to UTI with CRKP or ESBL-producing K. pneumoniae (7 and 8 days, respectively) were significantly longer than that for susceptible K. pneumoniae (1 day; P < 0.001). Clinical failure was observed for 8 patients (36%) with CRKP, 4 (18%) with ESBL-producing K. pneumoniae, and 9 (14%) with susceptible K. pneumoniae (P = 0.073). Microbiological failure was seen for 10 patients (45%) with CRKP, compared with 2 (9%) with ESBL-producing K. pneumoniae and 2 (3%) with susceptible K. pneumoniae (P < 0.001). In multivariable logistic regression analyses, CRKP was associated with greater odds of microbiological failure (versus ESBL-producing K. pneumoniae: odds ratio [OR], 9.36, 95% confidence interval [CI], 1.94 to 72.1; versus susceptible K. pneumoniae: OR, 31.4, 95% CI, 5.91 to 264). In conclusion, CRKP is associated with ICU admission, long length of stay, and microbiological failure among OTRs with UTIs. Greater numbers are needed to determine risk factors for infection and differences in meaningful endpoints associated with carbapenem resistance.

Risk factors for the acquisition of nosocomial infection with carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported all over the world. In this study, we aimed to investigate the risk factors for the acquisition of nosocomial CRKP infections. METHODS: We conducted a case-control study with data collected from thirty-nine patients with nosocomially acquired CRKP infection between July 2006 and July 2008. Controls were selected at a ratio of 1:2 from patients with nosocomial carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection and were matched with CRKP cases for site of infection and the date of hospital admission (± within 5 days). T test, chi-square test, and logistic regression were used for statistical analysis. RESULTS: Bivariable analysis showed that the age of the patients (P=0.038), days of hospital stay prior to isolation of Klebsiella pneumoniae (K. pneumoniae) (P=0.043), altered consciousness (P=0.007), intensive care unit (ICU) admission within two weeks (P=0.003), tracheal intubation (P=0.027), mechanical ventilation (P=0.009), number of changes in antibiotics≥4 (P=0.001), exposure to carbapenems (P = 0.002), exposure to fourth-generation cephalosporins (P=0.027), and exposure to piperacillin-tazobactams/cefoperazone-sulbactams (P=0.043) and glycopeptides (P=0.042) were related to CRKP infection. The multivariable analysis showed that ICU admission (within two weeks) [odds ratio (OR):4.68, 95% confidence intervals (CI):1.15-19.09, P=0.031], exposure to carbapenems (OR: 12.69, 95% CI: 2.09-77.10, P=0.006) and exposure to glycopeptides (OR: 3.57, 95% CI: 1.11-11.42, P=0.032) were independent risk factors for nosocomial CRKP infections. CONCLUSION: Several factors are related to CRKP infections. ICU admission (within two weeks) or prior exposure to carbapenems or glycopeptides are independent risk factors for the acquisition of nosocomial CRKP infections.

Evidence to support the therapeutic potential of bacteriophage Kpn5 in burn wound infection caused by Klebsiella pneumoniae in BALB/c mice.

The emergence of antibiotic-resistant bacterial strains is one of the most critical problems of modern medicine. Bacteriophages have been suggested as an alternative therapeutic agent for such bacterial infections. In the present study, we examined the therapeutic potential of phage Kpn5 in the treatment of Klebsiella pneumoniae B5055-induced burn wound infection in a mouse model. An experimental model of contact burn wound infection was established in mice employing K. pneumoniae B5055 to assess the efficacy of phage Kpn5 in vivo. Survival and stability of phage Kpn5 were evaluated in mice and the maximum phage count in various organs was obtained at 6 h and persisted until 36 h. The Kpn5 phage was found to be effective in the treatment of Klebsiella-induced burn wound infection in mice when phage was administered immediately after bacterial challange. Even when treatment was delayed up to 18 h post infection, when all animals were moribund, approximately 26.66% of the mice could be rescued by a single injection of this phage preparation. The ability of this phage to protect bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not due to a nonspecific immune effect. The levels of pro-inflammatory cytokines (IL-1beta and TNF-alpha) and anti-inflammatory cytokines (IL-10) were significantly lower in sera and lungs of phage-treated mice than phage untreated control mice. The results of the present study bring out the potential of bacteriophage therapy as an alternate preventive approach to treat K. pneumoniae B5055- induced burn wound infections. This approach not only helps in the clearance of bacteria from the host but also protects against the ensuing inflammatory damage due to the exaggerated response seen in any infectious process.

Acute pyelonephritis: clinical characteristics and the role of the surgical treatment.

The epidemiology of acute pyelonephritis (APN) has changed with time. Therefore we investigated the current clinical characteristics of APN and the significance of proper surgical management for treatment of 1,026 APN patients in South Korea for the past 5 yr. The male-to-female ratio was about 1:8. The peak ages of female patients were 20s (21.3%) and over 60s (23.7%), while that of male was over 60s (38.1%). The occurrence of sepsis was 10.1%. Complicated APN patients were 35.4%. Ninety-four patients (9.2%) needed urological procedures. The duration of the flank pain and of the costovertebral angle tenderness in complicated APN patients was statistically significantly longer than that with simple APN patients (4.3 vs. 3.4 days, 4.4 vs. 4.0 days). If flank pain and costovertebral angle tenderness sustain over 4 days, proper radiologic studies should be performed immediately with the consideration of surgical procedure. Also the resistance to antibiotics was increasing. As the sensitivities to ampicillin (27.2%) and trimethoprim/sulfamethoxazole (44.7%) of Escherichia coli and Klebsiella pneumoniae were very low, it is necessary to take the careful choice of antibiotics into consideration.

Aortoduodenal fistula complicated by acupuncture.

Recently, acupuncture has become a common therapeutic procedure for pain control worldwide. Although it has been repeatedly reported that acupuncture is effective and safe, several serious complications were also reported. In this article, we present a case of 68-year-old man who died of massive hematemesis resulting from aortoduodenal fistula (ADF), a rare complication of acupuncture therapy.

[Use of pentaglobin in the treatment of sepsis in the patient undergoing intraperitoneal hyperthermic chemotherapy]. / Utilizzo del pentaglobin nel trattamento della sepsi nel paziente sottoposto a chemioipertermia intraperitoneale (CIIP).

In patients subjected to cytoreduction and hyperthermic antiblastic peritoneal perfusion (HAPP), their immunocompromized conditions claim a very aggressive therapeutic approach in case of periotonitis and sepsis. Therefore, we use an adjuvant therapy of severe bacterial infections additional to antibiotic therapy by using Pentaglobin. It contains human plasma proteins, of which immunoglobulin at least 95%, with high rate of IgG, IgM and IgA, infused intravenously at 12 mL/h for 3 days continuously. From November 2000 to March 2003, we combined this approach for the treatment of peritonitis/sepsis in 11 patients. In 10 patients we obtained a complete control of the infective status in 8 days, while 1 patient died for MOFF. So, even with the exiguity of our casuistry, we obtained a better and more rapid clinical control of the patients respect to the previous period when the Pentaglobin was not used.

Catheter-related infections associated with home parenteral nutrition and predictive factors for the need for catheter removal in their treatment.

The inpatient and outpatient records were reviewed for 527 patients, including 138 children, who were discharged on home total parenteral nutrition and followed by the University of California, Los Angeles, home total parenteral nutrition service for a minimum of 1 week between April 1973 and October 1991. The total follow-up time was 1154 patient years; the median follow-up time was 206 days (range 7 to 6344 days). Thirty-six patients were followed for more than 10 years (median 12.7 years). Three hundred fifteen adults (but only four children) were never infected. A total of 427 catheter-related infections occurred, giving an overall infection rate of 0.37 per patient year (0.51 per patient year in children and 0.28 per patient year in patients followed for more than 10 years). Seventy percent of the infections overall were sepsis (0.26 per patient year); of those, 17% were exit site (0.06 per patient year), and 2% were tunnel (0.01 per patient year) infections. In children, 67% of the infections were sepsis (0.37 per patient year) and 24% were exit site (0.13 per patient year). Fifty-four different organisms were responsible, and 12% of the infections were polymicrobial in origin. Sixty percent of sepsis in all patients was caused by Gram-negative organisms (44% of the catheters were removed). Forty-three percent of sepsis in children was caused by Gram-negative organisms. Twenty-six percent of sepsis in all patients was caused by Gram-positive organisms (40% of the catheters were removed). Thirty-six percent of sepsis in children was caused by Gram-positive organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of ceftazidime-amikacin therapy for bacteremia and meningitis due to Klebsiella pneumoniae producing an extended-spectrum beta-lactamase.

A multiple trauma patient failed treatment with ceftazidime and amikacin for bacteremia and meningitis due to a Klebsiella pneumoniae strain that produced a novel, plasmid-mediated beta-lactamase. Both pre- and posttreatment isolates were resistant to ceftazidime (MIC, greater than or equal to 64 micrograms/ml) and various penicillins but not to other expanded-spectrum cephalosporins. The beta-lactamase had a pI of 5.25 and was encoded on a conjugal plasmid of approximately 150 kilobases. DNA hybridization studies indicated that the enzyme was a TEM derivative.

Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: comparison of pefloxacin, ciprofloxacin, and ofloxacin.

Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts.

Continuous versus intermittent administration of ceftazidime in experimental Klebsiella pneumoniae pneumonia in normal and leukopenic rats.

Experimental Klebsiella pneumoniae pneumonia was used to study the influence of cyclophosphamide-induced leukopenia on the relative therapeutic efficacy of continuous and intermittent (6-h intervals) administration of ceftazidime. The antimicrobial response was evaluated with respect to the calculated daily dose that protected 50% of the animals from death (PD50) until 16 days after the termination of a 4-day treatment. When ceftazidime was administered intermittently to leukopenic rats, the PD50 was 24.37 mg/kg per day, 70 times (P less than 0.001) the PD50 of 0.35 mg/kg per day for normal rats. Continuous administration of ceftazidime to leukopenic rats resulted in a PD50 of 1.52 mg/kg per day, four times (P less than 0.001) the PD50 of 0.36 mg/kg per day for normal rats. Continuous administration of ceftazidime in daily doses that protected 100% of normal and leukopenic rats from death resulted in serum levels of 0.06 and 0.38 micrograms/ml, respectively, whereas the MIC for the infecting K. pneumoniae strain was 0.2 micrograms of ceftazidime per ml. The effect of the duration of ceftazidime treatment by continuous infusion on the therapeutic efficacy in relation to the persistence of leukopenia was then investigated in leukopenic rats. The administration of 3.75 mg of ceftazidime/kg per day for 4 days protected all leukopenic rats from death, provided the circulating leukocytes returned at the end of antibiotic treatment. When leukopenia persisted for 8 days this ceftazidime treatment schedule resulted in the mortality of rats (P less than 0.05). However, when ceftazidime treatment was continued for 8 days, until the return of the leukocytes, there was no significant mortality (P greater than 0.05).

A randomized study of tobramycin plus ticarcillin, tobramycin plus cephalothin and ticarcillin, or tobramycin plus mezlocillin in the treatment of infection in neutropenic patients with malignancies.

Two hundred twenty-five patients with 358 febrile episodes were treated with tobramycin and ticarcillin (TT), tobramycin and mezlocillin (TM), or tobramycin, ticarcillin and cephalothin (TTC). There were no statistically significant differences in the response rates for patients who were proven to have infection (67% with TT, 69% with TTC and 53% with TM). Patients were more often cured of their infection if their neutrophil count rose during therapy. In this study, the addition of cephalothin to TT did not increase the frequency of azotemia (10% and 12%, respectively). Although mezlocillin has a broader spectrum of activity in vitro than ticarcillin, it was not more efficacious when combined with tobramycin than ticarcillin plus tobramycin for the treatment of infections in neutropenic patients.

Transient bacteremia associated with barium enema.

A group of 175 patients had barium enema. Pour-plate blood cultures were obtained immediately before and after the procedure and 5, 10, 15, and 30 minutes later. Bacteremia was demonstrable in 20 (11.4%) patients. In some, blood cultures were positive for as long as 15 minutes after barium enema; all were negative at 30 minutes. Among the bacteria associated with the 20 episodes of bacteremia were Escherichia coli, Klebsiella, enterococci, Proteus morganii, Bacteroides, and Veillonella. The incidence of bacteremia among patients with ulcerative colitis, regional enteritis, rectal polyps, colonic or rectal carcinoma, nonspecific diarrhea, or other lower intestinal tract disorders was not much different from patients free of rectosigmoid disease. The results of this study suggest that a history of recent barium enema may be important in patients who have endocarditis.