Al-Azhar University ‫جامعة االزهر‬

Faculty of Pharmacy (Boys) ‫(كلية الصيدلة )بنين‬

Cairo ‫القاهرة‬

RESEARCH PROJECT
Department: Microbiology and Immunology
Academic year: 2019/2020
Course name: Microbiology 2
Course code: PMI 322
Lecturers: Dr/Hmaedo Hefny
Dr/Al-Saeed Helal
Research project title: The clinical and economic impact of drug resistant infections
and impact on health acquired infections

STUDENT INFORMATION
Student Name: ‫أحمد محمد ابراهيم عبد السميع‬
Student Number: 2018026
e-mail: 3bsame3ahmed@gamil.com
Mobile number: 01120444261

STUDENT INFORMATION
Secret Code:
Degree :
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Al-Azhar University ‫جامعة االزهر‬
Faculty of Pharmacy (Boys) ‫(كلية الصيدلة )بنين‬
Cairo ‫القاهرة‬

Content

Topic Page No.

Introduction 3

4
Clinical and Economics outcomes.
Duration and Cost of Hospitalization. 5

Attributable Hospital Cost and Length of Stay Associated with Health

Care-Associated Infections Caused by Antibiotic-Resistant Gram- 5
Negative Bacteria.
Results of Clinical and Economic Impact of Bacteremia with Extended-
7
Spectrum-β-Lactamase-Producing Enterobacteriaceae.

Summary 9

References 10
Introduction

1.Over the last decade, efforts to fight multidrug-resistant ( MDR) microorganisms

have focused primarily on gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus and enterococci resistant to vancomycin. While a large number
of hospitals have taken more rigorous measures to control infections, drug companies
have developed new antimicrobial agents to combat these bacteria; This resulted in
several new compounds with novel action mechanisms, e.g. linezolid and daptomycin.
Paralleling the advances in gram-positive bacteria, infections caused by MDR gram-
negative bacilli have become a growing issue . In a recent report the American
Infectious Diseases Society specifically addressed three categories of gram-negative
MDR bacilli, i.e., extended-Escherichia coli and Klebsiella spp., MDR Pseudomonas
aeruginosa, and Acinetobacter spp., which are resistant to carbapenes. Unfortunately,
and contrary to what happened with gram-positive bacteria, no antibiotics were
produced specifically for gram-negative MDR bacilli from a new class. One could
argue that glycycline tigecycline is an exception to The above statement, but although
this drug has an in vitro activity against many MDR gram-negative bacilli, the drug
was not specifically developed for the treatment of infections caused by such bacteria .
Additionally, there is now an increasing number of reports of cases of infections
caused by gram-negative organisms for which there are no adequate therapeutic
options . Back to thisIn many parts of the world the preantibiotic era became a reality.
The aim of this report is to estimate the prevalence of infections caused by MDR
gram-negative bacilli, as well as the effects on mortality, hospital length of stay
(LOS), and increased hospital costs.

1
Research Project

2.Clinical and Economics outcomes.

2.1.Clinical outcomes.

Of 186 CR-BSI patients, 10 could not be balanced, as there were no control subjects
found that met the ICU stay requirement. Therefore, the matching procedure resulted
in a matched cohort study with 176 patients who had CR-BSI and 315 subjects of
control. Efficient matching for the year of admission (about 2 years) for 253 control
Patients, (80.3%). The catheter was removed from 154 CR-BSI patients (87.5 percent)
after the onset of the infection, and 127 (77.0 percent) of 165 patients received
adequate antimicrobial therapy. Following the onset of CR-BSI, additional renal
replacement therapy was needed, compared to the amount required by subjects in
control. Mortality rates in hospital with CR-BSIandmatched control Subjects were
respectively 27.8 percent and 26.0 percent (P p). The attributable mortality rate thus
amounted to 1.8 percent (95 percent CI,.672 to 10.0 percent). There were no
differences in mortality between CRBSI patients and matched control subjects.
Causative pathogen, monomicrobial or polymicrobial CR-BSI tests, timing of catheter
removal and antimicrobial therapy appropriateness.

2.2. Economics outcomes.

The economic performance data are summarized in table 2. CR-BSI patients endured
longer periods of mechanical ventilation and had longer ICU stay and hospitalization
durations. Total costs on hospital invoices were also higher for patients with CR-BSI,
as were the components related to the per diem rate, pharmacy expenses, and medical

2
expenses. The economic determinants differ. Following adjustment of hospitalization
duration and clinical covariates, linear regression analysis identified CR-BSI as
independently associated with increased costs.

3. Duration and Cost of Hospitalization.

After the launch of multidrug-resistant A. In the hospitalization, baumannii

bacteremia, 22 cases and 18 controls died; their matches were omitted, leaving only
21 case-control pairs for the subsequent cost review. The length of ICU stay was days
for cases and days 21.2 [23.3] 5.2 [7.3] for inspections); (hospital stay period (SSD)
P.001 was days for cases and days for con54.2 42.8 34.1 environ 30.5 trolleys. The
cost of hospitalization P p.006 was for cases and $9,348 for some $6,323 $4,865 for
some $4,015 trols; the cost of antibiotic therapy (SD) was $2,257 for cases and tests.
Thus, attributable to multidrug-resistant A, bac$1,361 $1,610 or $1,315 teremia.
Baumannii led to further hospitalization for 13.4 days and an extra cost of US$ 3,758
relative to bacteremia Non-multidrug -resistantA. baumannii.

4. Attributable Hospital Cost and Length of Stay Associated with

Health Care-Associated Infections Caused by Antibiotic-Resistant
Gram-Negative Bacteria.

4.1. MATERIALS AND METHODS.

A query of a larger database of all patients diagnosed with a HAI in our hospital
between 1998 and 2008 has created the database used for this analysis. All isolates
had undergone antimicrobial susceptibility testing using standard test methods in the
Clinical Microbiology Laboratory of the hospital, using standard methodology and

3
definitions. The report numbered 1,236 documents HAIs caused by pathogenic GNs.
Patients were excluded from the analysis if they had multiple infections during the
same admission period, incomplete financial data or lack of susceptibility data,
leaving data for evaluation for a total of 662 patients. In both the ICU and general
wards, data from the original database is obtained for patients and separated on the
basis of the five pathogenic Interesting Bacteria: Acinetobacter spp., E. Coli,
Klebsiella spp., Enterobacter spp., and Pseudomonas spp. Candidate risk factors and
covariates included MDR, age , gender, pneumonia diagnosis, ICU stay, neutropenia,
central venous line use, chemotherapy reception, use of a Foley catheter, total
parenteral nutrition (TPN), use of mechanical ventilation, transplantation, and HAIs of
interest: bloodstream infection (BSI), surgical site infection (SSI), other infections
(including UTI). Susceptibility to antibiotics has been denoted as susceptible,
intermediate or resistant and has not been tested. Financial data included total hospital
charges, which were provided through the hospital's patient accounting system. The
overall hospital cost for each individual patient Complete admission has been
determined. The overall hospital cost to patients with HAIs caused by GN pathogens
included drug costs, laboratory and medical tests, ICU stay, as well as other
procedures for patient care. All costs are reported in U.S. dollars for 2008. Estimates
of the cost of a hospital episode were based on changes to UB-92 and UB-04 (from
the 1982 Uniform Billing Act), Hospital billing (charge) information revised 1992 and
2004 using a hospital-wide cost-to-charge ratio. Using this method, the cost of
increasing hospitalization was measured as the sum of the billed charges contained in
the hospital billing records during the hospital case, and the total cost-to-charge ratio
for that year, available from the Medicare cost report. Best The cost of each infection
was common and was not due exclusively to the costs involved. The mathematical

4
multivariate analysis described below offers a summary of the cost evaluation
attributed to them.

5.Results of Clinical and Economic Impact of Bacteremia with

Extended- Spectrum-β-Lactamase-Producing Enterobacteriaceae.

One hundred ninety-eight patients were registered (99 cases and 99 controls). Of the
subjects, 56 percent were men, and 44 percent were women. The average age for this
was 74 ± 14. The average number of comorbid ities was two, with the most common
being cardiovascular disease (73%), malignancy (34%), and diabetes mellitus (30%).
For cases the pathogen distribution was the same and Checks: 23 percent E. Coli,
Klebsiella spp. 63 per cent and Proteus spp. 14 per cent. The causes of bacteremia
were as follows: urinary tract (37%), primary bacteremia (25%), pneumonia (16%),
intra-abdominal infection (15%), and line and wound infections (4%, respectively).
There were no gaps between groups in source of bacteremia.

5.1. Baseline characteristics of the cohort and univariate analysis.

The reference characteristics of the cases and controls as well as the univariate
analyzes conducted for each of the four regression modeling outcomes analyzed.
Cases and controls differed in the distribution of sex (cases, 65% male; controls, 47%
male; P = 0.02). There were no differences between the groups regarding the
frequency of comorbid conditions. More cases than monitors had before cultivation
The central venous catheter (45% vs. 20%; P < 0.001), the urinary catheter (81% vs.
60%; P = 0.002), the intensive care unit (22% vs. 8%; P = 0.009), the dialysis (13%
vs. 4%; P = 0.04), the instrumentation (55% vs. 26%; P < 0.001), the operation (31%
vs. 11%; P < 0.001), and the mechanical ventilation. More cases were admitted from

5
an institution than from home (27 per cent versus 14 per cent; P = 0.03) than controls.
More developed nosocomial bacteremia (62% vs. 27%; P < 0.001). In cases the
median duration of stay until bacteremia was greater than for controls (8 days versus 1
day; P < 0.001). More cases than controls had poor functional status (66% vs. 47%; P
= 0.01) and had received more recently Antibiotics (66% versus 17%; P < 0.001). On
average, cases were sicker than controls (mean McCabe severity score on admission
for cases was 2.13 versus 1.83 for controls; P = 0.001), but the groups had similar
proportions with a high McCabe score (22% versus 17%; P = 0.48).

6
Summary
Knowledge of the clinical and economic effects of antimicrobial resistance is useful
for shaping policies and actions in health care facilities, directing policy-makers and
funding agencies, identifying individual patient prognosis and increasing interest in
developing new antimicrobial agents and therapies. There are a number of important
things that need to be taken into consideration while planning or Interpreting reports
of antimicrobial resistance based clinical and economic outcomes. Some of the most
common problems is how expense is accurately calculated. Although imperfect,
existing data show that there is a link between antimicrobial resistance in
Staphylococcus aureus, enterococci and Gram-negative bacilli and increased mortality
, morbidity, length of the bacteria Hospitalization, and treatment prices. Patients with
antimicrobial-resistant organism infections have higher costs (US$ 6000–30,000) than
patients with antimicrobial-susceptible organism infections; the cost differential is
even greater when patients with antimicrobial-resistant species are compared to non-
infection patients. Knowledge of Small Budgets The clinical and economic effects of
antibiotic-resistant bacterial infections, combined with the benefits of specific
strategies aimed at reducing those infections, would allow optimal control and
enhance patient safety. Throughout this review the authors explore a number of
important problems that need to be discussed when designing or analyzing clinical
and economic outcomes studies Linked to antimicrobial resistance. Representative
literature is reviewed on the associations between antimicrobial resistance in specific
pathogens and adverse outcomes including increased mortality, hospital stay duration
and cost.

7
References

1. Giske, Christian G., et al. "Clinical and economic impact of common multidrug-
resistant gram-negative bacilli." Antimicrobial agents and chemotherapy 52.3
(2008): 813-821.(1)
2. Blot, Stijn I., et al. "Clinical and economic outcomes in critically ill patients with
nosocomial catheter-related bloodstream infections." Clinical Infectious Diseases
41.11 (2005): 1591-1598.(2)
3. Lee, Nan-Yao, et al. "Clinical and economic impact of multidrug resistance in
nosocomial Acinetobacter baumannii bacteremia." Infection Control & Hospital
Epidemiology 28.6 (2007): 713-719.(3)
4. Mauldin, Patrick D., et al. "Attributable hospital cost and length of stay associated
with health care-associated infections caused by antibiotic-resistant gram-
negative bacteria." Antimicrobial agents and chemotherapy 54.1 (2010): 109-115.
(4)
5. Schwaber, Mitchell J., et al. "Clinical and economic impact of bacteremia with
extended-spectrum-β-lactamase-producing Enterobacteriaceae." Antimicrobial
agents and chemotherapy 50.4 (2006): 1257-1262.(5)