THE IMPROPER USE OF ANTIBIOTICS

With the emergence of superbugs (antibiotic resistant bacteria), the proper use of antibiotics is now more important than ever. Dying from hospital acquired bacteria is now the 10^th leading cause of death in the United States.

The physician should exercise “antibiotic stewardship” when prescribing antibiotics and use the Culture and Sensitivity (C & S) test as a tool – prescribing antibiotics from “prior experience” as Dr. Michael Hori was proud to admit did not work. These tools should be used properly by a hospital and their physicians – the shotgun approach didn’t and doesn’t work.

I am now wondering when Dr. Michael Hori said this to me on January 14 if he was talking about his experience with the other patient at Valley that acquired the Burkholderia and Pseudomonas on December 27 after Mark did (when I asked him why he didn’t give Mark the Ceftazidime [per Dr. Mary J Vancleave’s dictation] or Ticarcillin/Clavulanic acid per the C & S – he “felt” a newer drug had more potential). I am sure this other patient wasn’t given the Dexamethasone (contraindicated with infection) they gave Mark.

I watched the results from uncontrollable bacteria kill Mark. You do not want to die this way.

I will always wonder why Dr. Suzanne Krell kept cancelling the orders for the Ceftazidime when Dr. Michael Hori was supposed to be charge of antibiotics.

What is antibiotic stewardship?

Antimicrobial (or antibiotic) stewardship programs are interventions designed to ensure that hospitalized patients receive the right antibiotic, at the right dose, at the right time, and for the right duration.

What is a Culture and Sensitivity (C & S) Test?

A culture is done to find out what kind of organism (usually bacteria) is causing an illness or infection. A sensitivity test checks to see what kind of medicine, such as an antibiotic, will work best to treat the illness or infection

WARNING: Prescribing Zosyn (piperacillin and tazobactam) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of development of drug-resistant bacteria.

Nosocomial (hospital acquired) pneumonia caused by Pseudomonas aeruginosa should be treated in combination with an aminoglycoside.

Did VMC doctors prescribe Zosyn without bacteria present? You bet they did – just right before they intubated Mark (and gave him the bacteria).

January 3 is the only day Mark is given Zosyn with an aminoglycoside (Amikacin) – after Valley gave Mark the 4^th bacteria - Pseudomonas.

The Initial Blood cultures and antibiotics

3 blood cultures were taken before antibiotics were administered and ALL were negative (actually, all 42 blood cultures Valley did while Mark was hospitalized were negative). VMC doctors thought Mark was going through a sepsis event when instead Mark was going through medication withdrawal.

November 10:  Hospital admit

November 10:  Blood culture taken

November 11:  (2) Blood cultures taken

November 11:  Antibiotic Zosyn/Piperacilin (6 units) given

November 12:  Antibiotic Zosyn/Piperacilin (6 units) given

November 13:  Antibiotic Zosyn/Piperacilin (9 units) given

November 14:  Antibiotic Zosyn/Piperacilin (9 units) given

November 14 (4): Blood culture taken

The Bacteria Begin

November 11 – Mark goes through medication withdrawal and has a toxic drug interaction with the MAO inhibitor and Fentanyl/Versed.

November 12 – Mark is intubated around 1:00 am by Dr. Ichiro Otsu

November 14 18:45 - VALLEY C & S REPORT

Culture Respiratory
Specimen description   Tracheal aspirate
Special requests            None
Gram Stain                      4+ Mixed flora predominantly gram positive cocci
Culture                             3+ other cells
                                          3+ Enterobacter cloacae
                                          3+ staphylococcus aureus, MRSA

Susceptibility, MIC
Organism                         3+ Enterobacter cloacae
Aztreonam                       Susceptible
Cefazolin                         Resistant
Ceftriaxone                     Susceptible
                                          Cefotaxime predicated with Ceftriaxone
Gentamicin                     Susceptible
Levofloxacin                   Susceptible – receives 11/14, 11/15, 11/20
Piperacillin/Tazobactam     Susceptible – receives 11/11 – 11/16
Trimethoprim/Sulfa        Susceptible
Ertapenem                      Susceptible
Amp/Amoxicillin             Resistant
Ampicillin/Sulbactam    Intermediate
                                          Augmentin predicted with Amp/Sulbactam

Susceptibility
Organism                         3+ staphylococcus aureus, MRSA
Method                             MIC
Clindamycin                   Susceptible
Tetracycline                    Susceptible
Trimethoprim/Sulfa        Susceptible
Vancomycin                    Susceptible – receives 11/14, 11/16

Mark also receives Meropenem (11/18 – 11/22) and Collagenase (11/19) which are not listed on the C & S.

November 19 – Dr. Stephanie Nunez re-intubates Mark due to respirator equipment failure

November 21 20:00 - VALLEY C & S REPORT (The Enterobacter is now gone – now Burkholderia shows up).

Culture Respiratory

Specimen description   Tracheal aspirate
Special requests            None
Gram Stain                      2+ Epithelial cells seen
                                          1+ Mixed flora
Culture                             2+ staphylococcus aureus, MRSA
                                          2+ Bukholderia cepacia
Susceptibility
Organism                         2+ staphylococcus aureus, MRSA
Method                             MIC
Clindamycin                   Susceptible
Tetracycline                    Susceptible
Trimethoprim/Sulfa        Susceptible
Vancomycin                    Susceptible – receives 11/22, 11/23 – 11/24

Susceptibility

Organism                         2+ Bukholderia cepacia
Method                             Kirby Bauer
Minocycline                    Susceptible
Trimethoprim/Sulfa        Resistant
Ceftazidime                     Susceptible
Meropenem                     Intermediate – receives 11/18 – 11/22

Mark also receives Metronidazole (a 2C9 inhibitor 11/23 – 11/27) and Cefepime (11/23 – 12/4) which are not listed on the C & S.

NOTE: Metronidazole is a 2C9 inhibitor which should not be given to Mark

Dr. Mary J Vancleave mentions in her dictation that the Burkholderia that is susceptible to Ceftazidime - which should have been given at this point.

November 25 12:50 - VALLEY C & S REPORT

Culture Respiratory

Specimen description   Tracheal aspirate
Special requests            None
Gram Stain                      2+ PMN’s seen
                                          2+ Other cells
                                          No organisms seen
Culture                             2+ Bukholderia cepacia
                                          2+ staphylococcus aureus, MRSA

Note from VMC lab: This MRSA has an MIC for Vancomycin that is equal to or greater than 1 microgram per microliter. This has been associated with an increased risk of treatment failure.

Susceptibility

Organism                         2+ staphylococcus aureus, MRSA
Method                             MIC
Clindamycin                   Susceptible
Tetracycline                    Susceptible
Trimethoprim/Sulfa        Susceptible
Vancomycin                    Susceptible – receives 11/25 (see note above)

Susceptibility

Organism                         2+ Bukholderia cepacia
Method                             Kirby Bauer
Trimethoprim/Sulfa        Resistant
Meropenem                     Intermediate – receives 11/18 – 11/22
Minocycline                    Susceptible
Ceftazidime                     Susceptible

Mark also receives Metronidazole (a 2C9 inhibitor 11/23 – 11/27); Cefepime (11/23 – 12/4); Zyvox (11/25 – 12/5) and Fluconazole (a 2C9 inhibitor 11/30 and 12/1) which are not listed on the C & S.

NOTE: Metronidazole and Fluconazole are 2C9 inhibitors and should not be given to Mark

December 1 01:35 - VALLEY C & S REPORT

Culture Respiratory

Specimen description   Tracheal aspirate
Special requests            None
Gram Stain                      2+ PMN’s seen
                                          1+ Epithelial cells seen
                                          2+ Gram negative rods
                                          1+ Other cells
Culture                             3+ Bukholderia species Presumptive cepacia
                                          1+ staphylococcus aureus, MRSA

Note from VMC lab: This MRSA has an MIC for Vancomycin that is equal to or greater than 1 microgram per microliter. This has been associated with an increased risk of treatment failure.

Susceptibility

Organism                         1+ staphylococcus aureus, MRSA
Method                             MIC
Clindamycin                   Susceptible
Tetracycline                    Susceptible
Trimethoprim/Sulfa        Susceptible
Vancomycin                    Susceptible

Susceptibility

Organism                         3+ Bukholderia species Presumptive cepacia
Method                             Kirby Bauer
Ceftazidime                     Susceptible
Trimethoprim/Sulfa        Resistant
Minocycline                    Susceptible
Meropenem                     Intermediate

Mark instead receives Cefepime (11/23 – 12/4); Zyvox/Linezolid (11/25 – 12/5); Levofloxacin (12/1) and Caspofungin (12/2 – 12/3) which are not listed on the C & S.

December 2 – Dr. Gabriel Alperovich performs a tracheotomy and peg tube insertion

December 4 13:00 - VALLEY C & S REPORT (The MRSA is now gone)

Culture Respiratory

Specimen description   Tracheal aspirate
Special requests            None
Gram Stain                      1+ PMN’s seen
                                          1+ Epithelial cells seen
                                          3+ Gram negative rods
                                          3+ Other cells
                                          No mixed flora seen
Culture                             3+ Bukholderia species Presumptive cepacia
                                          1+ Gram positive organism unable to further
                                          isolate

Susceptibility

Organism                         3+ Bukholderia species Presumptive cepacia
Method                             Kirby Bauer
Ceftazidime                     Susceptible
Minocycline                    Susceptible
Meropenem                     Intermediate
Trimethoprim/Sulfa        Resistant

Mark instead receives Cefepime (11/23 – 12/4); Zyvox/Linezolid (11/25 – 12/5); Collagenase (12/6) which are not listed on the C & S.

ALL ANTIBIOTICS ARE STOPPED 12/7 TO 12/9 PER DR. MICHAEL HORI (Note from above: the 1+ gram positive is Pseudomonas).

December 9 10:00 - VALLEY C & S REPORT

Culture Wound

Specimen description   area around trach
Special requests            None
Gram Stain                      4+ PMN’s seen
                                          3+ RBC’s seen
                                          2+ Gram negative rods
Culture                             3+ Bukholderia cepacia group
                                          3+ Pseudomonas aeruginosa

Susceptibility

Organism                         3+ Pseudomonas aeruginosa
Method                             MIC
Cefepime                         Susceptible
Gentamicin                     Resistant
Levofloxacin                   Resistant
Piperacillin/Tazobactam     Susceptible
Aztreonam                       Susceptible

Susceptibility

Organism                         3+ Bukholderia species Presumptive cepacia
Method                             Kirby Bauer
Meropenem                     Susceptible
Minocycline                    Susceptible
Ceftazidime                     Susceptible
Trimethoprim/Sulfa        Resistant

Mark receives Caspofungin (12/12 – 12/14); Doxycycline (12/12, 12/13, 12/15 – 12/26); Metronidazole (a 2C9 inhibitor 12/12 – 12/16); Vancomycin (12/10, 12/12, 12/14, 12/17, 12/19 – 12/21) which are not listed on the C & S.

NOTE: Metronidazole is a 2C9 inhibitor and should not be given to Mark

December 14 23:00 - VALLEY C & S REPORT – all antibiotics will now be under Dr. Michael Hori’s direction per focus note

Culture Respiratory

Specimen description   Bronchial wash LLL
Special requests            None
Gram Stain                      4+ PMN’s seen
                                          1+ Gram negative rods
Culture                             3+ Bukholderia cepacia group
                                          3+ Pseudomonas aeruginosa

Susceptibility

Organism                         3+ Pseudomonas aeruginosa
Method                             MIC
Cefepime                         Susceptible – receives 12/10, 12/12, 12/13,
                                          12/15, 12/16, 12/18 – 12/21)
Gentamicin                     Resistant
Levofloxacin                   Resistant
Piperacillin/Tazobactam     Susceptible
Aztreonam                       Susceptible

Susceptibility

Organism                         3+ Bukholderia species Presumptive cepacia
Method                             Kirby Bauer
Ceftazidime                     Susceptible
Imipenem                        Susceptible
Meropenem                     Intermediate
Trimethoprim/Sulfa        Intermediate

Mark also receives Caspofungin (12/12 – 12/14); Doxycycline (12/15 – 12/26); Metronidazole (a 2C9 inhibitor 12/12 – 12/16); Vancomycin (12/14, 12/17, 12/19 – 12/21); Acyclovir (12/17) and Collagenase (12/17) which are not listed on the C & S.

NOTE: Metronidazole is a 2C9 inhibitor and should not be given to Mark

December 19 21:00 - VALLEY C & S REPORT - all antibiotics are under Dr. Michael Hori’s direction (The bacteria are increasing)

Culture Respiratory

Specimen description   Bronchial wash
Special requests            None
Gram Stain                      4+ PMN’s seen
                                          2+ other cells
                                          4+ Mixed flora
Culture                             4+ Bukholderia cepacia group
                                          4+ Pseudomonas aeruginosa
                                          No usual respiratory floa
Susceptibility
Organism                         4+ Pseudomonas aeruginosa
Method                             MIC
Cefepime                         Intermediate – receives 12/18 – 12/21
Gentamicin                     Resistant
Levofloxacin                   Resistant
Piperacillin/Tazobactam     Susceptible
Aztreonam                       Intermediate

Susceptibility

Organism                         4+ Bukholderia species Presumptive cepacia
Method                             Kirby Bauer
Meropenem                     Susceptible
Ceftazidime                     Susceptible
Trimethoprim/Sulfa        Resistant
Minocycline                    Susceptible

Mark also receives Doxycycline (12/15 – 12/26) and Vancomycin (12/19 – 12/21) which are not listed on the C & S.

December 25 12:45 - UW C & S REPORT

This C & S was originally collected by VMC on December 25; this was received by the UW on December 29. Why 4 days? I could have driven this to the UW in an hour, even with snow on the ground. The UW sends the C & S back to VMC (faxed) on January 1. VMC doesn’t review these results (which are discussed in daily rounds) until January 3 (and Dr. William Park only says he has not seen them yet).

This test was performed at THE UNIVERSITY OF WASHINGTON. Notice the difference in the UW versus the Valley studies above. Why didn’t Valley send this to the UW in the first place?

Culture Respiratory

Specimen description                     Bronchial wash, Left main bal
Special requests                              None
Gram Stain                                        4+ PMN’s seen
                                                            4+ Gram negative rods
Culture                                               1+ Bukholderia cepacia group
                                                            3+ Pseudomonas aeruginosa

Susceptibility
Pseudomonas aeruginosa Microtiter MIC panel
Trimeth Sulfamethoxazole             4 Resistant
Tobramycin                                       32 Resistant
Gentamicin                                       64 Resistant
Amikacin                                           8 Susceptible – receives 12/25, 1/3
Aztreonam                                         16 Intermediate
Colistin                                              2 Susceptible – receives 12/25 – 12/27, 12/29
                                                            – 12/20, 1/5 – 1/6, 1/10, 1/14 to 1/15
                                                            (nebulizer 12/25 – 1/2, 1/6 – 1/8)
Ceftazidime                                       8 Susceptible
Meropenem                                       8 Intermediate – receives 1/2, 1/12, 1/13
Imipenem                                          16 Resistant
Ticarcillin/clavulanic Acid              64 Susceptible
Piperacillin/Tazobactam                 16 Susceptible – receives 1/3 – 1/11
Ciprofloxacin                                    8 Resistant
Minocycline                                      32 Resistant
Chloramphenicol                             64 Resistant
Cefepime                                           16 Intermediate
Levofloxacin                                     16 Resistant

VMC must have asked the UW about using Doxycycline and the UW responds: No Clinical and Laboratory Standards Institute (CLSI) interpretive criteria available for this organism and antibiotic combination.

Susceptibility

Burkholderia cepacia Microtiter MIC panel
Trimeth Sulfamethoxazole             1 Susceptible
Tobramycin                                       128 Resistant
Gentamicin                                       64 Resistant
Amikacin                                           64 Resistant – receives 12/25, 1/3
Aztreonam                                         4 Susceptible
Colistin                                              32 Resistant – receives 12/25 – 12/27, 12/29
                                                            – 12/20, 1/5 – 1/6, 1/10, 1/14 to 1/15
                                                            (nebulizer 12/25 – 1/2, 1/6 – 1/8)
Ceftazidime                                       2 Susceptible
Meropenem                                       2 Susceptible – receives 12/25 – 1/2, 1/12,
                                                            1/13
Imipenem                                          16 Resistant
Ticarcillin/clavulanic Acid              64 Intermediate
Piperacillin/Tazobactam                 4 Susceptible
Ciprofloxacin                                    2 Intermediate
Minocycline                                      1 Susceptible
Chloramphenicol                             8 Susceptible
Cefepime                                           2 Susceptible
Levofloxacin                                     2 Susceptible

VMC must have asked the UW about using Doxycycline and the UW responds: No Clinical and Laboratory Standards Institute (CLSI) interpretive criteria available for this organism and antibiotic combination.

Mark also receives Doxycycline (12/25 - 12/26); Vancomycin (12/25, 1/4 - 1/8); Vancomycin oral (1/8 – 1/10); and Metronidazole (a 2C9 inhibitor 1/7 – 1/16) which are not listed on the C & S.

NOTE: Metronidazole is a 2C9 inhibitor and should not be given to Mark

December 25

Dr. William Park says he will order an older antibiotic; he said the tracheotomy tube had puss all the way down it and they cleaned as much as they could out. I tell Dr. Park Mark will be able to fight the bacteria. (I note that Colistin is started again)

Dexamethazone is started on December 26 (to January 7): Contraindications: Bacterial, viral, and fungal disease may progress more easily and can become life-threatening. Dexamethasone is a 2C9 inducer.

January 11

Dr. Suzanne Krell cancels the order for Mark to receive Ceftazidime and starts Meropenem.

January 12

Dr. Michael Hori cancels the order for Zosyn and starts the Ceftazidime again – the pharmacy clarifies the order.

January 13

This order is missing from the medical records - someone had cancelled the Ceftazidime

January 14

Dr. Michael Hori cancels the order for Meropenem and starts the Ceftazidime again – the pharmacy clarifies the order.

January 15

This order is missing from the medical records – someone had cancelled the Ceftazidime as it is not on the bill

January 16

Mark dies.