Fabio Tumietto

Programma Aziendale Epidemiologia e Controllo del Rischio Infettivo Correlato alle Organizzazioni Sanitarie

-

Clinica Malattie Infettive - Bologna

La profilassi, la diagnosi e la scelta della terapia antibiotica

SEPSI E INFEZIONI IN GRAVIDANZA 17-18 ottobre 2014

Prevalence of antimicrobial use (percentage of patients receiving at least one antimicrobial agent) in European hospitals, by country, ECDC PPS 2011–2012

He observed that maternal mortality rates, mostly attributable to puerperal fever, were substantially higher in one clinic compared with the other (16% versus 7%). He also noted that doctors and medical students often went directly to the delivery suite after performing autopsies and had a disagreeable odour on their hands despite handwashing with soap and water before entering the clinic. He hypothesized therefore that “cadaverous particles” were transmitted via the hands of doctors and students from the autopsy room to the delivery theatre and caused the puerperal fever. As a consequence, Semmelweis recommended that hands be scrubbed in a chlorinated lime solution before every patient contact and particularly after leaving the autopsy room. Following the implementation of this measure, the mortality rate fell dramatically to 3% in the clinic most affected and remained low thereafter.

Infection control: the story begins

4

Percentage of resistant isolates among isolates from HAIs with known antimicrobial susceptibility testing (AST) results, by species and by country, ECDC PPS 2011–12

Infection control: scope of interventions

In the wards…the standard of care

Contamination of Stethoscopes and Physicians’ Hands After a Physical Examination.

Y Longtin et al, Mayo Clin Proc 2014;89: 291-299

Se la flora microbica presente sulle mani si vedesse così,

non ci sarebbero le infezioni associate all’assistenza.

Infection control: scope of interventions

Surgical site infections

MRSA rates and hand hygiene compliance by quarter ; Scotland

0

10

20

30

40

50

60

70

80

90

100

Jan

07-M

ar 0

7

Apr 0

7-Ju

n 07

Jul 0

7-Se

p 07

Oct 0

7-Dec

07

Jan

08-M

ar 0

8

Apr 0

8-Ju

n 08

Jul 0

8-Se

p 08

Oct 0

8-Dec

08

Jan

09-M

ar 0

9

Apr 0

9-Ju

n 09

Jul 0

9-Se

p 09

Oct 0

9-Dec

09

Jan

10-M

ar 1

0

Apr 1

0-Ju

n 10

Jul 1

0-Se

p 10

Oct 1

0-Dec

10

Jan

11-M

ar 1

1

Han

d h

yg

ien

e %

co

mp

lian

ce

0.00

0.05

0.10

0.15

0.20

0.25

MR

SA

rate

per

1000 o

ccu

pie

d b

ed

s

HH compliance

MRSAR= -0.847

THE EQUATION OF THE INFECTIOUS RISK

BACTERIAL LOAD x VIRULENCE

HOST IMMUNITY

= INFECTIOUS RISK

+ DRUG RESISTANCE

HOST IMMUNITY

= INFECTIOUS RISK

Every Operation is an Experiment in Bacteriology

Surgical Antimicrobial Prophylaxis - definition

Surgical AMP refers to a very brief course of an antimicrobial agent initiated just before an operation begins. AMP is not an attempt to sterilize tissues, but a critically timed adjunct used to reduce the microbial burden of intra-operative contamination to a level that cannot overwhelm host defenses.

Prevention of SSI’s

Perioperative antimicrobial prevention measures

Maintain normal blood sugar levels

Hyper oxygenation

Maintain normal body temperature

Hair removal immediately prior to operation using electric clippers

Hand washing

Good surgical technique

Control of host-related risk factors

Antibiotics Antibiotics

THE FIVE MAIN TOPICS OF SURGICAL ANTIBIOTIC PROPHYAXIS

• INDICATION

• TIMING OF ADMINISTRATION

• OVERALL LENGHT OF ADMINISTRATION

• DRUG DOSAGE

• DRUG CHOICE

NRC Wound Classification

Clean Surgical Procedures NO PROPHYLAXIS Clean Contimated Procedures PROPHYLAXIS Contaminated Procedures THERAPY Dirty Procedures THERAPY

Two well recognized AMP indications for such clean operations are:

1. Any intravascular prosthetic material or prosthetic joint will be

inserted

2. Any operation in which an incisional or organ space SSI would

pose catastrophic risk

Cardiac surgery

Neurosurgical Operations

Prosthetic arterial grafts

Revascularization of lower extremity

THE FIVE MAIN TOPICS OF SURGICAL ANTIBIOTIC PROPHYAXIS

• INDICATION

• TIMING OF ADMINISTRATION

• OVERALL LENGHT OF ADMINISTRATION

• DRUG DOSAGE

• DRUG CHOICE

CINETICA di CRESCITA BATTERICA

dopo CONTAMINAZIONE INTRA-OPERATORIA

Popolazione batterica UFC/mL

PROCEDURA CHIRURGICA

TEMPO

2 -6 ore 3 -5 giorni

contaminazione

colonizzazione

INFEZIONE

Periodo vulnerabile

Troppo precoce Timing corretto Troppo tardiva

100

10

1

Incisione cutanea

MIC

Siero

Interstizio tessuti

C>MIC per tutto l’intervento

TIMING

Methods. Data about SSI and potential prophylaxis-, patient-, and procedure-related risk factors were prospectively collected for 1922 patients who underwent elective total hip arthroplasty in 11 hospitals that participated in the Dutch intervention project, Surgical Prophylaxis and Surveillance. Multivariate logistic regression analysis was performed to correct for random variation among hospitals.

The association between the timing of administration of prophylaxis and the incidence of SSI

Overall infection rate: 2.6%

Antibiotic Prophylaxis and the Risk of Surgical Site Infections following Total Hip Arthroplasty: Timely Administration Is the Most Important Factor van Kasteren MEE et al, Clin Infect Dis 2007; 44:921–7

THE FIVE MAIN TOPICS OF SURGICAL ANTIBIOTIC PROPHYAXIS

• INDICATION

• TIMING OF ADMINISTRATION

• OVERALL LENGHT OF ADMINISTRATION

• DRUG DOSAGE

• DRUG CHOICE

Implementing 1-Dose Antibiotic Prophylaxis for Prevention of Surgical Site Infection Nunes S et al, Arch Surg. 2006;141:1109-1113

Patients: Surgery was performed on 6140 consecutive patients from February 2002 through October 2002 (period 1) and 6159 consecutive patients from December 2002 through August 2003 (period 2). Studied surgeries included orthopedic, gastrointestinal, urology, vascular, lung, head and neck, heart, gynecologic, oncology, colon, neurologic, and pediatric surgeries. Intervention: Decreasing the 24-hour prophylactic antibiotic regimen to 1-dose antibiotic prophylaxis. Main Outcome Measures: Surgical site infections in both periods measured by in-hospital surveillance and Post-discharge surveillance; compliance with 1-dose prophylaxis; and costs with cephazolin.

1° period (24 h prophylaxis)

6140 surgical procedures

2° period (single dose)

6159 surgical procedures

SSI rates (%) 2 2,1

THE FIVE MAIN TOPICS OF SURGICAL ANTIBIOTIC PROPHYAXIS

• INDICATION

• TIMING OF ADMINISTRATION

• OVERALL LENGHT OF ADMINISTRATION

• DRUG DOSAGE

• DRUG CHOICE

2013

Vaginal preparation with povidone-iodine solution immediately before

cesarean delivery reduces the risk of postoperative endometritis.

This benefit is particularly realized for women undergoing cesarean delivery

with ruptured membranes.

As a simple, generally inexpensive intervention, providers should consider

implementing preoperative vaginal cleansing with povidone-iodine before

performing cesarean deliveries.

SEVERE SEPSIS

SEPSIS

T° > 38.3 / < 36°C

pulse rate > 90 beats/minute

respiratory rate > 20 breaths/min

WBC > 12.000 / < 4.000/mmc

glycemia > 120 mg/dL

lactemia > 2 mmol/L

plasma C-reactive protein >2 SD above the normal value

plasma procalcitonin > 2 SD above the normal value

refilling > 2 seconds

altered mental status

hypotension (systolic < 90 mmHg)

lactemia > 4 mmol/L

organ disfunction/s

hypotension despite 20-40 ml/kg 1^h

SEPSIS DEFINITION

SEPTIC SHOCK

organ dysfunction /s

Laboratories that will suggest organ dysfunction include …

PaO2 (mm Hg)/Fio2 2.0 mg/dL or Creatinine increase >0.5 mg/dL,

INR> 1.5,

PTT> 60 seconds,

Platelets < 100,000/mL,

Total bilirubin> 4 mg/dL,

Glasgow Coma Scale score < 13,

The clinical value of a correct antimicrobial choice

IN ORDER TO GUARANTEE THE BEST ANTIMICROBIAL OPTIONS

EPIDEMIOLOGICAL DRIVEN EMPIRICAL THERAPY

PK/PD DRIVEN THERAPY

TARGETED THERAPY AS SOON AS POSSIBLE

DON’T FORGET MICROBIOLOGICAL SPECIMENS

PATIENT’S CLINICAL CONDITION

RISK FACTORS FOR SPECIFIC MICROORGANISM and/or RESISTENCE PATTERNS

THE DECISION TREE…

SOURCE

PRESUMED MICROBIOLOGY

CLINICAL SEVERITY

LOCALIZATION of LESIONS

FEASIBILITY of CONTROL SOURCE

RISK FACTORS for MAJOR RESISTANCE PATTERNS

Sepsi Ampicillina 2 gr ogni 4-6 ore oppure Ceftriaxone 2 gr /die oppure Piperacillina sodica /tazobactam: dose carico 8+1 gr (in 1 ora); mantenimento 4 gr + 0.5 gr ogni 6 ore (infondere ogni dose in 4 ore). Sepsi severa Piperacillina sodica /tazobactam: dose di carico di 9 gr in 1 h; mantenimento con 18 gr in IC/24 h, iniziando l’infusione dopo la fine della dose di carico + Teicoplanina 12-15 mg/Kg di peso ogni 12 ore per le prime 4 dosi; a seguire 8-10 mg/Kg di peso ogni 24 ore, previa determinazione della concentrazione ematica (Cmin) del farmaco (20-30 mg /L)

INFEZIONI CUTANEE SUPERFICIALI

INFEZIONI CUTANEE PROFONDE NON NECROTIZZANTI

NECROTIZZANTI

INFEZIONI NECROTIZZANTI ESTESE AI TESSUTI MOLLI (fasce/muscoli)

INFEZIONI nei SOGGETTI IMMUNOCOMPROMESSI

SIRS PRESENTE SIRS ASSENTE

La terapia sistemica è accessoria

La terapia sistemica è necessaria Le scelte devono privilegiare la semplicità

La terapia sistemica è necessaria Le scelte possono basarsi sulla semplicità

La terapia sistemica è fondamentale e deve essere di massima performance

Ten days after an uncomplicated vaginal delivery at home, a 35-year-old woman presented to the ED with a 16 h history of severe, burning right breast pain, and 2 h of diarrhoea and vomiting. On examination, her temperature was 37.9°C, she was tachycardic (120/min), and her blood pressure was 100/70 mm Hg. Her chest was clear, with oxygen saturation 96% on air. Blood tests showed aleucocytosis of 11・3×10⁹/L and a high C-reactive protein (CRP) of 61 mg/L. The diagnosis was mastitis. Despite two intravenous doses of amoxi/clav acid, her pain worsened and the erythema continued to extend. Over the next 8 h, pain prevented her from breastfeeding; she was hypotensive and had rigors and persisting pyrexia (38.0°C). Blood tests showed leucocytosis (12・5×10⁹/L) and high CRP (183 mg/L) and creatine kinase (150 IU/L).

NECROTIZING

SKIN / SOFT TISSUE INFECTION

SUSPICION!

PAIN DISPROPORTIONATE TO SKIN CLINICAL FINDINGS

NOT DEMARCATE, RAPIDLY EVOLVING LESION

Intravenous clindamycin (2.4 g four times daily) and imipenem (1.0 g four times daily) was started according to the hospital’s protocol; IV polyspecific immunoglobulin (20 g) was also given. 11 h after presentation, our patient was transferred for emergency surgical debridement. Microbiological examination of specimens showed chains of gram-positive cocci, later yielding GAS. On day 13, her breast wound was resurfaced with a split skin graft. In December, 2003, her breast was reconstructed with a subpectoral tissue expander. When last seen in April, 2005, the patient was happy with her breast reconstruction.

Group A streptococcal necrotising fasciitis masquerading as mastitis

Tillett R L et al, Lancet 2006; 368: 174

83 83

100 100

14

48

4

41

%

deep infections

superficial infections

deep infections (+surgery)

superficial infections (+surgery)

clinda non clinda

Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive S. pyogenes infection. Zimbelman J et al, Pediatr Infect Dis J 1999;18:1096-100

retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Children's Hospital. Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections

The antimicrobial therapy puzzle

The Antimicrobial Therapy Puzzle: Could Pharmacokinetic-Pharmacodynamic Relationships Be Helpful in Addressing the Issue of Appropriate Pneumonia Treatment in Critically Ill Patients?

F Pea, P Viale CID 2006;42:1764–71

Fabio Tumietto

Programma Aziendale Epidemiologia e Controllo del Rischio Infettivo Correlato alle Organizzazioni Sanitarie

-

Clinica Malattie Infettive - Bologna

La profilassi, la diagnosi e la scelta della terapia antibiotica

SEPSI E INFEZIONI IN GRAVIDANZA 17-18 ottobre 2014