tazobactam in patients with serious infections due to resistant Pseudomonas aeruginosa

Accepted Manuscript Title: CLINICAL EXPERIENCE WITH CEFTOLOZANE/TAZOBACTAM IN PATIENTS WITH SERIOUS INFECTIONS DUE TO RESISTANT PSEUDOMONAS AERUGINOSA Authors: Marc Xipell, Sandra Paredes, Leticia Fresco, Marta Bodro, Francesc Marco, JA. Mart´ınez, Alex Soriano PII: DOI: Reference:

S2213-7165(18)30012-2 https://doi.org/10.1016/j.jgar.2018.01.010 JGAR 579

To appear in: Received date: Revised date: Accepted date:

30-10-2017 23-12-2017 14-1-2018

Please cite this article as: Marc Xipell, Sandra Paredes, Leticia Fresco, Marta Bodro, Francesc Marco, JA.Mart´ınez, Alex Soriano, CLINICAL EXPERIENCE WITH CEFTOLOZANE/TAZOBACTAM IN PATIENTS WITH SERIOUS INFECTIONS DUE TO RESISTANT PSEUDOMONAS AERUGINOSA (2010), https://doi.org/10.1016/j.jgar.2018.01.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

CLINICAL

EXPERIENCE

PATIENTS

WITH

WITH

SERIOUS

CEFTOLOZANE/TAZOBACTAM

INFECTIONS

DUE

TO

IN

RESISTANT

PSEUDOMONAS AERUGINOSA

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Marc Xipell¹, Sandra Paredes¹, Leticia Fresco¹, Marta Bodro¹, Francesc Marco²,

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JA. Martínez¹, Alex Soriano¹.

Affiliation: ¹Infectious Diseases Department, Hospital Clínic-IDIBAPS. ²Microbiology

N

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Department; Hospital Clínic-ISGLOBAL; University of Barcelona.

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

M



Ceftolozane/tazobactam (C/T) has promising results in Pseudomonas aeruginosa infections. Prospective studies are needed for supporting its use in off-label indications. Better results for respiratory infections were observed in our study with 2/1gr q8h of C/T, compared with lower doses.

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

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HIGHLIGHTS

ABSTRACT

OBJECTIVES: The incidence of infections caused by multidrug resistant

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Pseudomonas aeruginosa (MDR-PA) has become a concern of increasing relevance nowadays. Ceftolozane/tazobactam is a novel 5th generation cephalosporin/β-lactamase inhibitor combination with activity against MDR-PA.

METHODS: We retrospectively reviewed the clinical records of all patients diagnosed from May 2016 to May 2017 with an infection due to a MDR-PA treated with C/T. RESULTS: 23 patients with 24 episodes of infection due to MDR-PA were

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included. The MIC of C/T against MDR-PA ranged from 0.75 to 8 µg/mL. In 14 cases (58%) the use of C/T was off-label including 8 respiratory tract infections and 6 skin and soft tissue infections while in 10 cases the use was for approved

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indications including 7 urinary tract infections and 3 intraabdominal infections. C/T was the first line therapy in only 3 cases with a mean duration of treatment

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of 9.3 (SD 4) days and it was associated with other active drug (aminoglycoside

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or colistin) in 16 cases. The global clinical cure rate was 87.5% (21 out of 24

A

episodes) and the 6-week mortality rate was 22% (5 out of 23 patients) being

M

higher in respiratory tract infections (37%). In these infections, 3 patients received 2/1gr every 8h and were cured without mortality while 3 out of 5 patients (60%)

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receiving 1/0.5gr every 8h died.

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CONCLUSION: C/T had good clinical responses in different types of infection, including both FDA accepted and off-label indications and our results support the

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use of higher doses in respiratory tract infections.

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INTRODUCTION

The incidence of infections caused by microorganisms with resistance to conventional antibiotics has become a concern of increasing relevance nowadays. In the last few years, new therapeutic drugs have been developed. Ceftolozane is a novel 5th generation cephalosporin with a potent activity against

Pseudomonas aeruginosa (PA) due to its high affinity for PBP1b and PBP3, highouter membrane permeability, stability against AmpC β-lactamase and it is less affected by efflux pumps than other antibiotics. The combination with tazobactam, an established β-lactamase inhibitor, improves its activity against some

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Enterobacteriaceae producing β-lactamase[1]. The aim of our study was to describe the characteristics and outcomes of 23

patients with 24 infections caused by multi-drug (MDR), extensively-drug (XDR)

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or pan-drug resistant (PDR) PA treated with ceftolozane/tazobactam (C/T) in our

U

center. Three of these patients were also described in a recent case report[2].

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MATERIAL AND METHODS

M

We retrospectively reviewed the clinical records of all patients diagnosed from May 2016 to May 2017 of a serious infection due to a resistant PA strain in our

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institution who were treated with C/T for at least 72h. Serious infections were considered as those requiring hospitalization. Patients were selected from the

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registry of the Department of Pharmacy. The following variables were collected

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from the electronic medical records: sex, age and comorbidities, focus of infection, empirical treatment, antibiotic susceptibilities, renal function, dose and duration of C/T, associated antibiotics, other therapeutic interventions and

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outcome. The decision to use C/T as well as the dose and duration prescribed were at the discretion of the treating physicians. The different types of infections were defined and classified following National Healthcare Safety Network criteria[3]. Clinical success was defined as a resolution of signs and symptoms of the infection (as reported by treating physicians), and no recurrence of the

infection in the same location during admission. Microbiologic eradication was defined as negative cultures for PA after 72 hours of therapy when repeated cultures from the same source were available. Antimicrobial susceptibility testing was performed by disc diffusion methodology. The E-test method was used to determine the in vitro activity of C/T. We used the Clinical and Laboratory

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Standards (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria to define susceptibility or resistance to antimicrobial

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agents[4,5]. MDR, XDR and PDR were defined according ECDC definitions[6].

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The institutional review board of our institution approved the study.

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RESULTS

A

In the time period reviewed, we identified 24 episodes of infection in 23 patients

M

due to resistant PA: 79% XDR-PA (19/24), 16.6% MDR-PA (4/24) and 4% PDR-

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PA (1/24). These were predominantly men (78%), with a mean age of 61.6 (SD 13) years. The mean duration of treatment with C/T was 14.3 (SD 9.4) days and

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the 6-week mortality rate was 21.7%. Patients were divided into four groups, according to the infection foci. The characteristics of the patients are shown in

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Table 1. The minimum inhibitory concentration (MIC) of C/T was available for all strains except one.

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The first group included 8 patients with respiratory tract infection, 4 of which were pneumonias and 4 tracheobronchitis. Out of the four patients with pneumonia two survived and both were initially treated with 2/1gr every 8h (q8h) of C/T. The other two patients received 1/0.5gr q8h during six and eight days, respectively. The first one died during treatment and the second, despite clinical and radiological

improvement, and normalization of inflammatory parameters, one month later had bacteremia due the same strain, not treated with C/T, and finally died. All 4 patients with pneumonia received combined treatment, in the first case with intravenous amikacin and the other three with nebulized amikacin and/or colistin.

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Four patients had tracheobronchitis during intensive care unit stay. All 4 were cured, but one patient died because of his underlying disease after total resolution of clinical manifestations, improvement of inflammatory parameters, and negative

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respiratory cultures. The mean treatment duration was 8.5 (SD 3) days. One patient received 2/1g q8h of C/T during the first 4 days, and 1/0.5 g q8h for 2

U

additional days. All the others received 1/0.5 q8h of C/T. In three cases C/T was

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combined with nebulized colistin and in the other with nebulized and intravenous

A

tobramicin.

M

The second group included 6 patients with skin and soft tissue infections including

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a diabetic foot infection, a Fournier gangrene, a surgical wound infection of a cardiac assist device, an infection of osteosynthesis material, a mediastinitis, and

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a submandibular fasciitis with bacteremia in a woman with severe bone marrow aplasia. The mean duration of treatment in this group was 19 (SD 8) days.

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Surgical debridement was performed in all patients, and the ventricular device and the osteosynthesis material were removed. All but one were cured with 1/0.5gr q8h of C/T. Failure was observed in the neutropenic patient with

A

submandibular fasciitis due to XDR-PA. The patient remained bacteremic and finally died despite doubling the C/T dose (2/1g q8h) and the addition of 3 MU q8h of colistin. Interestingly, the C/T MIC of the subsequent blood strains switch from 1 to 256 µg/mL. The patient with Fournier gangrene suffered a urinary tract

infection by the same PA 15 days after being cured (this episode is included in the next group). The third group included 7 patients with complicated urinary tract infections (cUTI). Three patients with renal failure were successfully treated with 700/250mg q8h of C/T, and one with 1/0.5gr q8h during 2 days and subsequently with

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0.5/0.25gr q8h. One patient with advance liver cirrhosis suffered a UTI and was

initially treated with 1/0.5g q8h of C/T in monotherapy but the patient developed

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septic shock and died as a consequence of the infection.

The fourth group included 3 patients with intraabdominal infections: a liver

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abscess, a cholangitis with bacteremia, and an abdominal abscess secondary to

M

A

the outcome was favorable in all three.

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a gastrectomy suture leak. Surgical drainage was necessary in two patients and

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DISCUSSION

C/T has been approved for the treatment of complicated urinary tract and

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intrabdominal infections with a clinical success rate of about 80% in both

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indications[7,8]. However, the number of infections due to resistant-PA included in these studies was limited. The main interest of ceftolozane is its potent activity against PA, as was shown in the PACTS program[9] where C/T was tested

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against 3851 PA strains isolated from 32 US hospitals between 2012 and 2015, and demonstrated a susceptibility rate of 97%. In addition, 607 and 363 were MDR-PA and XDR-PA, respectively, and the susceptibility rate for each group was 84.9% and 76.9%, respectively. Recent IDSA and ATS guidelines[10] strongly recommend against monotherapy with an aminoglycoside in the

treatment of hospital and ventilator-associated pneumonia due to PA, and the same approach is reasonable for other severe infections. Therefore, it is urgent to evaluate the efficacy of C/T in other indications. Our retrospective revision shows that C/T is increasingly being used for the treatment of resistant-PA in offlabeled clinical indications, including 8 respiratory infections and 6 skin and soft-

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tissue infections that represented 58% of all the infection episodes included in

this review. Interestingly, the global clinical cure rate was 87.5% (21 out of 24

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episodes) and the 6-week mortality was 22% (5 out of 23 patients), even taking into account that in all cases except 3, C/T was initiated after several days of other previous antibiotic regimens. These percentages are similar to other clinical

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experiences[11–13] and are better than other studies using colistin for the

N

treatment of PA infections that showed success rates of about 60%[14,15]. In

A

addition, according to a retrospective analysis, bacteremia is associated with a

M

poor prognosis among patients treated with colistin, with a failure rate of 75% (6

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out of 8 patients) [14], while the failure rate in our patients with bacteremia was only 1 out of 5 (20%). However, the number of patients is low and it is necessary

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to have more experience to confirm these preliminary results.

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One of the most frequent and severe infections caused by PA are respiratory infections[16]. In our series, there were 8 patients, 4 with pneumonia and 4 with tracheobronchitis. Cure was achieved in 7 cases, including 3 out of 4 pneumonia

A

episodes and the mortality rate was 37.5% (3 out of 8). Three patients received 2/1gr q8h and were cured without mortality while 3 out of 5 patients (60%) receiving 1/0.5gr q8h died. C/T is a time-dependent antibiotic and the best predictor of its bactericidal activity (2 log reduction) is a C/T ƒT>MIC of 3040%[17,18]. Accordingly, a population pharmacodynamic model in plasma and

epithelial lining fluid (ELF) demonstrated that 2/1gr q8h of C/T is necessary to achieve a 90% in plasma and 85% in ELF probability of target attainment (≥50% ƒT>MIC) for MICs ≤8 µg/mL[19]. These results were used for the design of an ongoing clinical trial of C/T in pneumonia (NCT02070757). However, while

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waiting for the definitive results our data supports the use of high dose of C/T. P. aeruginosa also causes skin and soft tissue infections, particularly surgical site infections and in immunesuppressed. In our study, there were 6 cases, with a

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positive outcome in 5 of them. Surgical treatment is essential in this type of

infection and it was performed in all 6 cases. One patient, with severe neutropenia

U

and submandibular fasciitis had persistent bacteremia and died as a

N

consequence of the infection. Interestingly, baseline PA had a MIC of 1 µg/mL

A

but the strain isolated in the follow-up blood cultures had a MIC 256 µg/mL. There

M

are two potential explanations: 1) the patient had multiple PA strains and the predominant phenotype was eradicated by C/T, with resistant strains becoming

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the predominant phenotype in the repeated blood cultures, or 2) resistant mutants were selected during treatment. The frequency of resistant mutants to C/T is very

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low (<10-10)[20] but an in vitro model demonstrated the potential selection of

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resistant mutants when the C/T ƒT>MIC was between 10 and 30%[17]. Resistant mutants had a 2-8xMIC and only in case of hyper-mutator strains it would be possible to select strains with a higher MIC[21]. To know the exact mechanism is

A

of utmost importance since in the first situation clinical failure could not be attributed to C/T while it could be in the second situation. Unfortunately, clonal relationship between strains was not available but the most likely explanation, according to the big difference between the MICs, is the presence of two different strains, one susceptible and one resistant to C/T.

The major limitations of our study are its retrospective nature, and the presence of different foci, doses and antibiotic combinations that limit the analysis. However, considering the severity and high mortality rate of infections due to PA, it is necessary to have clinical data about the efficacy of a new cephalosporin with

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a potent activity against resistant-PA. In conclusion, our data shows the potent activity of C/T against resistant-PA including MDR, XDR and PDR strains with MIC ranging from 0.75 to 8 µg/mL.

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C/T treatment had good clinical responses in different clinical situations including

both FDA accepted indications and off-label indications and support the use of

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higher doses in respiratory tract infections. Future studies should address the

Declarations

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Funding: No funding.

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A

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benefit of early initiation of C/T among patients with risk factors for resistant-PA.

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Ethical Approval: Not required

Competing interests: A. Soriano has received honoraria as a speaker from

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MSD. The authors have no other relevant conflicts of interest.

Acknowledgments MSD provided medical writing support but was not involved in the content of the manuscript.

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[21]

Cabot G, Bruchmann S, Mulet X, Zamorano L, Moyà B, Juan C, et al.

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Pseudomonas aeruginosa ceftolozane-tazobactam resistance development requires multiple mutations leading to overexpression and structural modification of AmpC. Antimicrob Agents Chemother 2014;58:3091–9. doi:10.1128/AAC.02462-13.

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Table 1. BAS: bronchial aspirate; C/T: ceftolozane/tazobactam; F: female; GFR: glomerular filtrate rate (at the moment of initiating C/T); HCV: hepatitis C virus; IV: intravenous; M: male; MIC: minimun inhibitory concentration; MR: magnetic resonance; MRSA: meticilin-resistant Staphylococcus aureus; MU: million units; P/T: piperacilline/tazobactam; PA: Pseudomonas aeruginosa. *To simplify the table, only antibiotics sensitive to the strain or with intermediate sensitivity (with MIC in brackets) have been included; the remaining antibiotics were resistant.

Pneumon ia (sputum)

Merope nem

A

Alcoholic liver cirrhosis Child A, esophageal varices. Orotracheal intubation

Alcoholism with ischemic hepatitis, rhabdomyolysis and acute tubular necrosis. Orotracheal intubation Critical patient myopathy, Chronic Obstructive Pulmonary Disease, acute respiratory failure with orotracheal intubation and posterior tracheostomy

No

52

Tracheob ronchitis (sputum and tracheal aspirate)

Piperacil line/tazo bactam and nebulize d tobrami cin

Tracheob ronchitis (BAS)

Merope nem and colistin iv

Tracheob ronchitis (BAS)

C/T

Tracheob ronchitis (tracheal aspirate, BAS)

Piperacil lin/tazo bactam and amikacin iv, and nebulize d colistin

Amik acin Colist in C/T (2) (XDR)

Amik acin Cefta zidim e (8) Colist in Amik C/T acin (1) Colist (XDR) in C/T (1.5) (XDR) Tobra mycin Colist in C/T (8) (XDR)

1/0.5g q8h 6 days

1/0,5g q8h 8 days

Amikaci n iv 1g q24h 11 days (adjusti ng doses Amikaci accordin n g nebulize plasmati d c levels) 500mg/ 12h

Surg ical inte rven tion

Microbi ological eradicat ion

Outcome

No

Yes

Cured

No

Colistin nebulize d (2MU/8 h 6d + 1MU/8h 3d) + Amikaci n 500mg/ 12h Colistin nebulize nebulize d d 8 days 2MU/8h 6 days

2/1gr q8h for 3 days, follow ed by ceftazi dime 2gr q8h for 3 days

No

>90

No

>90

Ente roba cter cloa cae (BAS )

>90

No

70

Serr atia marc esce ns (trac heal aspir ate)

>90

1/0.5g q8h 8 days

2/1g q8h for 4 days follow ed by 1/0.5g r q8h 2 days 1/0.5g q8h 7 days

1/0.5g q8h 13 days

Tobram ycin iv 5 mg/kg q24h 4 days, and nebulize d tobramy cin Colistin 2MU/8h nebulize d9 days, and amikaci n Colistin nebulize nebulize d d 500mg/ 2MU/8h 12h 2 7days days Colistin nebulize d 2MU/8h 10 days

Patient manifested his willingness to reject aggressive measures and died. Cured. 33 days later presented bacteremia due the same PA, not treated with C/T, and died.

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>90

2/1g q8h 10 days follow ed by 1/0,5g q8h 5 days

Other active antibiot ics

No

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Amik acin Cefta zidim e (8) Colist in C/T (1) Amik (XDR) acin Cefta zidim e (8) Colist in C/T (1) (XDR)

MRS A (BAS )

>90

C/T dose and durati on

No

No data

No

No data

Cured

No

Yes

Cured

No

No data

Cured

No

No

Cured

Yes

Cured. Patient died 25 days later because his underlying disease

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Pneumon ia (sputum)

Ceftazidi me, ciproflox acin, nebulize d amikacin

acin Colist in C/T (0.75) (XDR)

No

GFR (ml / min /1. 73 m2)

N

Merope nem and linezolid

Poly micr obial (sam ple)

M

F / 4 9

B-cell Lymphoma with ureteral, intestinal and ovaric infiltration. Obstructive uropathy with requirement of bilateral nephrostomy. Chemotherapy. Tracheotomy

Pneumon ia (BAS)

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Diabetes mellitus, alcoholic liver cirrhosis Child B, bleeding esophageal varices, pacemaker.

M / 6 1

Merope nem, linezolid and fluconaz ol

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Respiratory Tract Infections

Ischemic heart disease. Hepatorenal polycystic with renal and hepatic transplantation, Common Variable Immunodeficiency with monthly administration of immunoglobulins, Burkitt Lymphoma stadium IV

M / 7 7

M / 6 4

Pneumon ia (sputum, blood cultures)

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Bladder tumor. Radical cystoprostatectomy with Bricker reconstruction. Fecaloid peritonitis due to accidental perforation of ileum during surgery. Chronic Obstructive Ileum resection, M Pulmonary Disease, terminal ileostomy. / arterial hypertension, 6 atrial fibrillation. 9 Admission for extense ischemic stroke.

M / 4 9

Empirica l treatme nt

Comorbidities

M / 7 8

M / 5 2

Focus of infection (samples )

Susce ptibili ty (MIC of C/T in µg/m L)* Amik acin Colist in C/T (1,5) (XDR) Amik

A

S e x A g e

No

F / 8 1

Type 2 diabetic mellitus, and femoral osteosynthesis material

Infection of osteosynt esis material Mediasti (deep nitis after samples biologic during aortic surgery) valve replacem ent surgery (Deep sample from open wound)

Ceftazidi me

Clindami cin

Merope nem

PT

F / 8 0

Diabetes mellitus, Chronic Obstructive Pulmonary Disease , cardiac valvular insufficiency

Surgical site infection (Swab)

Fournier gangrene . (abscess fluid, blood culture)

Merope nem

Urinary tract infection (urine culture)

C/T

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A

M / 2 6

Acute myeloblastic leukaemia treated with chemotherapy. Admitted for bone marrow allotransplantation in neutropenic phase

Colist in Amik acin C/T (2) (XDR)

Amik acin Colist in C/T (2) (XDR) Amik

No

>90

77

1/0,5g q8h 12 days

Amikaci n 1g q24h 5 days followe d by colistin 3MU q8h 6 days

No

Yes

Amikaci n 1g single dose

Cured

Impl ant rem oval and surg ical deb ride men t

No data

Persistent bacteremia and selection of a C/T resistant mutant with a MIC of 256 µg/mL. The patient died as a consequenc e of the infection Cured

Surg ical deb ride men t

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No

1/0,5g q8h 6 days follow ed by 2/1g q8h 5 days

Am puta tion

No

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M / 6 8

Idiopathic dilated cardiomyopathy with left ventricular assist device, and implantable cardioverterdefibrillator.

Merope nem and amikacin

Amik acin Colist in C/T (1) (XDR)

Ciproflo xacin iv 400mg q8h 10 days

U

Submand ibular fasciitis with bacterem ia (Blood culture)

>90

1/0.5g r q8h 14 days

N

F / 4 9

Severe bone marrow aplasia, admitted for allogenic bone marrow transplantation. Graft failure. Bacteremia due to PA treated with amikacin and ceftazidime

Merope nem

51

1/0,5g q8h 31 days

No

Impl ant rem oval

No data

Cured

72

1/0,5g q8h 3 weeks

Amikaci n iv 500mg q24h during 2 weeks

Surg ical deb ride men t

Yes

Cured

Amikaci n iv 1g q24h 11 days

Surg ical deb ride men t

No

No

No (Blood cultures were negative but wound coloniza tion persist) Yes

Cured. Patient had a urinary tract infection by the same P. aeruginosa 15 days later (next case) Cured

A

Infected ulcer (swab)

Ente roba cter cloa cae (swa b)

M

Diabetes mellitus type II with ketoacidosis. Foot ulcer

acin Colist in Cefta zidim e (8) C/T (1) (XDR)

ED

Skin and soft tissue infections

M / 6 1

Amik acin Cipro floxac in Colist in C/T (No data) (MDR )

Amik acin Cefta zidim e Colist in P/T Amik (16) acin C/T Cefta (1) zidim (MDR e ) Colist in P/T (16) C/T (1) (MDR )

Kleb siella penu moni ae (Dee p sam ple duri ng surg ery)

No

84

No

>90

2/1g single dose and 1/0,5g q8h 25 days 1/0,5g q8h 14 days

M / 7 4

Colistin

Urinary tract infection (Urine culture)

Amikaci n and colistin (ev)

Colist in C/T (1.5) (XDR)

Linezolid , metroni dazole, colistin.

Amik acin Colist in C/T (3) (XDR)

Merope nem, teicopla nin and amikacin

Colist in Amik acin C/T (1) (XDR)

Arterial hypertension, Chronic Obstructive Pulmonary Disease, alcoholism, congestive heart failure. Admitted because of bilateral pneumonia Liver cirrhosisdue duetoto Staphylococcus HCV, colonaureus adenocarcinoma with hepatic metastases. Subtotal colectomy, chemotherapy and resection of affected hepatic segments and cholecystectomy

M / 4 4

Hepatic transplantation secondary to sclerosing cholangitis

Amik acin (16) C/T (4) (PDR)

Hepatic abscess secondar y to biliary leakage (abscess fluid)

Septic shock due to cholangiti s (blood culture), with image in the cholangio -MR of an abscess of 14mm in relation to the biliary tract

63

1/0.5 q8h 7 days

20

700/2 50mg q8h 15 days

No

No

Kleb siella pneu moni ae (urin e) and Ente roco ccus faec alis (drai nage fluid )

No

Ente roco ccus faeci um (abs cess fluid ) Esch erich ia coli (blo od cultu res)

Amikaci n single dose 1g iv

No

No data

Cured

No

No

IP T

700/2 50mg q8h 8 days

Yes

Yes

SC R

Postoperative period of second kidney transplantation from deceased donor, complicated with trombothic microangyopathy

Urinary tract infection and deep surgical site infection with bacterem ia (blood, urine culture and drainage fluid)

Piperacil line/tazo bactam

Amik acin Colist in P/T (6) C/T (2) (MDR )

40

No

Colistin iv 2MU q8h 4 days

Patient developed septic shock and died.

No

Yes

Cured

No

No

Yes

Cured

No

No

Yes

Cured

Colistin 2 MU q8h iv 10 days

Perc utan eou s drai nag e

No data

Cured

No

No

Yes

Cured

U

Urinary tract infection (Urine culture)

No

No

Cured. Ultrasound showed total resolution of the abscess.

N

Prolonged hospitalization due to acute necrotizing pancreatitis, complicated with ischemic colonic stenosis. Colostomy

A

Intraabdominal infections

M / 6 8

culture)

C/T (1) (XDR)

29

A

M / 6 7

C/T

Amik acin Colist in C/T (1.5) Colist (XDR) in

No

700/2 50mg q8h 25 days

20

M

M / 6 3

edematous decompensation, and encephalopathy

Merope nem

Amik acin Colist in C/T (4) (XDR)

ED

Urinary tract infections

M / 5 1

Diabetes mellitus II, arterial hypertension, chronic kidney disease stage III due to renovascular disease. Renal stentliver in right renal Alcoholic cirrhosis artery Child C, with ascitic and

Merope nem

PT

M / 6 5

CC E

M / 6 8

Chronic kidney disease due to hypertension, kidney transplantation, Chronic Obstructive Pulmonary Disease

Urinary tract infection + orchiepid idymitis with abscess (Urine culture) Urinary tract infection in the context ofUrinary urinary catheter tract (Urine infection culture) (Urine

27

46

>90

1/0,5g q8h 19 days

1/0,5g q8h 2 days follow ed by 0.5/0. 25gr q8h 8 days 1/0,5g q8h 6 weeks

1/0,5g q8h 4 weeks

Gastrectomy for gastric carcinoma, with suture leakage, needing surgical reintervention. Subsequently presented an epigastric collection

Abdomin al abscess (abscess fluid and ascites)

Ceftazidi me and colistin

Ente roco ccus faeci um (abs cess fluid )

>90

1/0.5g q8h 9 days

No

Perc utan eou s drai nag e

No data

Cured

A

CC E

PT

ED

M

A

N

U

SC R

IP T

F / 5 4

Amik acin Colist in C/T (1,5) (XDR)