MIDG Linda Chew

Infectious Diseases Registrar

Royal Hobart Hospital

CASE

66 year old Tasmanian man

Past medical history

AMI 2007 with PCI stent

COPD, ex smoker

Diet controlled T2DM

Obesity

Gastric laparoscopic banding 2010

Anxiety/Depression

Chronic back pain

Not on steroids or immune suppressants

CLINICAL PRESENTATION

Increasing exertional dyspnoea since April 2015

Admission into HDU June 2015 for aspiration

pneumonia in the setting of persistent vomiting

No causative pathogen found

Lap band deflated

Conventional antibiotic therapy for aspiration

pneumonia

Discharged after 10 days

CURRENT ADMISSION

Readmitted in July 2015 with persisting

respiratory symptoms

Clinical diagnosis of ongoing aspiration pneumonia

Commenced on IV piperacillin+tazobactam

De-escalated to oral amoxycillin+clavulanate after

5 days

CT CHEST

Multifocal consolidation

Dilated oesophagus with food residue

GASTROGRAFFIN STUDY

• Dilated distal

esophagus

• Narrowing at

the GE junction

at the level of

the gastric lap

band

DAY 7

Aerobic blood culture positive from day of admission

Gram positive rods, branching appearance

Gram stain ZN stain

PROGRESS

Further investigations:

Sputum sent off for AFB – AFB +++

HIV test – Negative

Continued spiking fevers on Augmentin DF

Day 11; Empirical anti-mycobacterial therapy commenced whilst waiting formal ID/sensitivities Clarithromycin 500mg BD

Ethambutol 15mg/kg daily

Rifampicin 600mg daily

Day 12: Lap band removal via laparoscopic approach

D17: ID OF MYCOBACTERIA

Mycobacteria fortuitum complex

Commenced on:

IV Amikacin

Cefoxitin with probenecid

whilst awaiting susceptibility results

Clarithromycin, ethambutol and rifampicin

therapy ceased

CASE SUMMARY

66 year old man with M. fortuitum pulmonary

infection and bacteraemia in the setting of

aspiration secondary to gastric lap band

Gastric lap band removed

Commenced on 2 drug regime for M. fortuitum,

amikacin and cefoxitin, whilst awaiting sensitivities

NON TUBERCULOUS/ATYPICAL MYCOBACTERIA

Approximately 50 species identified in 1997

By 2006, more than 125 species catalogued

Increasing number of clinically significant species

Ubiquitous in environment – soil & water

Incidence rates 1.0 – 1.8 cases per 100,000

persons in most industrialized countries, MAC

being most common [Horsburgh CR Jr, Epidemiology of MAC, NY: Marcel Dekker 1996]

CDC: NONTUBERCULOUS MYCOBACTERIA REPORTED

TO THE PUBLIC HEALTH LABORATORY INFORMATION

SYSTEM BY STATE PUBLIC HEALTH LABORATORIES:

UNITED STATES, 1993–1996

NTM isolated:

75% Pulmonary

5% bloodstream

2% skin/soft tissue

0.4% lymph node isolates

Pathogenic species per 1,000,000 population:

MAC :29 - 36 isolates

M. fortuitum: 4.6 – 6 isolates

M. kansasii: 2 – 3.1 isolates

CDI ATYPICAL MYCOBACTERIA NATIONAL

SURVEY, 2000

Data from 80 laboratories across Australia

1.8 cases per 100,000 population - 1,441 isolates

in year 2000

Clinical disease:

79% Pulmonary

10% Soft tissue

4% Lymphatic

7% Other (pleural fluid, blood, urine & unspecified)

Most common isolates: MAC, M. fortuitum, M.

abscessus, M. marinum, M. kansasii, M. chelonae,

M. haemophilum

A SPATIAL EPIDEMIOLOGICAL ANALYSIS OF NONTUBERCULOUS

MYCOBACTERIAL INFECTIONS IN QUEENSLAND, AUSTRALIA,

BMC INFECTIOUS DISEASES 2014

MICHAEL P CHOU ET AL

NTM data from the Queensland Mycobacterial Reference Laboratory over 10 year period (2001 – 2011)

6,599 NTM notifications

Clinical disease: 80% pulmonary, 20% extrapulmonary

NTM species: M. intracellulare 34.9%

M. avium 10.2%

M. fortuitum 7.5%

M. abscessus 7.4%

M. kansassi 2.8%

M. chelonae 2.8%

M. gordonae 2.5%

Other/unspeciated 31.9%

RHH EXPERIENCE: NTM ISOLATED

2010 - 2015

Total cases NTM = 126

M. avium complex (MAC): 42% M. avium: 27%, M. intracellulare: 13%

M. gordonae: 16%

M. heckeshornese: 6%

M. abscessus: 5%

M. fortuitum complex: 4%

M. chimaera 3%

M. kansasii: 2%

M. lentiflavum 2%

Other/ unspecified: 20%

Disease type : 90% Pulmonary

RUNYON CLASSIFICATION

Runyon Group Pigmentation Growth Examples

Photochromogen Yellow pigment

in light, no

colour in the

dark

>7 days M. kansasii

M. marinum

Scotochromogen Yellow pigment

without light

exposure

>7 days M. gordonae

Non-

photochromogen

No pigment

regardless of

light exposure

>7 days M. avium –

intracellulare

M. haemphilum

Rapid growers <=7 days M. abscessus

M. fortuitum

complex

M. chelonae

M. mucogenicum

RAPIDLY GROWING MYCOBACTERIA

Forms colonies within 7 days

Persist in the environment through biofilm

formation

More than 50 species

Catheter related bloodstream infections and

surgical wound site infections most common form

of nosocomial infections

Common community infections include soft tissue

infections secondary to footbaths, tattoos and

piercings

M. FORTUITUM COMPLEX

Rapid growing mycobacteria

Colonies: Transparent to cream-coloured smooth

with branching, filamentous extensions

Most commonly causes soft tissue infections

Cause of pulmonary disease in a specific subset of

patients with gastroesophageal disorders and

chronic vomiting

Issues of clinical significance if isolated –

pathogenic or colonization?

GRIFFITH ET AL, CLINICAL FEATURES OF PULMONARY

DISEASE CAUSED BY RAPIDLY GROWING

MYCOBACTERIA,

REV RESPIR DIS 1993

150 cases of RGM pulmonary cases over a 15

year period at Mycobacteria/Nocardia Research

Laboratory of the University of Texas Health

Center (1976 – 1982)

Associated medical conditions

Previous mycobacterial disease 18%

Bronchiectasis 11%

CF 6%

Gastroesophageal disorder with chronic

vomiting 6%

Malignancy (lung and other) 6%

COPD 5%

GRIFFITH ET AL, CLINICAL FEATURES OF PULMONARY

DISEASE CAUSED BY RAPIDLY GROWING

MYCOBACTERIA,

REV RESPIR DIS 1993

CXR FEATURES

Pattern:

Interstitial 37%

Interstitial/alveolar 40%

Reticulonodular 36%

Cavitation 16%

Multilobular (=>3 lobes) >50%

Bilateral 77%

Predominantly upper lobes

GRIFFITH ET AL, CLINICAL FEATURES OF PULMONARY

DISEASE CAUSED BY RAPIDLY GROWING

MYCOBACTERIA,

REV RESPIR DIS 1993

PULMONARY ISOLATES

Most common M. abscessus 82% followed by M.

fortuitum

Both occurred as commonly in the subgroup of

patients with gastro-esophageal diseases

GRIFFITH ET AL, CLINICAL FEATURES OF PULMONARY

DISEASE CAUSED BY RAPIDLY GROWING MYCOBACTERIA,

REV RESPIR DIS 1993

TREATMENT

Of M. fortuitum infections, only one failed treatment

In those with gastroesophageal disorders and chronic vomiting, surgical intervention to curtail vomiting and aspiration contributed to successful therapy

M. abscessus more difficult to eradicate and responded best to surgical resection of localized disease

Death rate as a result of their lung disease:

M. abscessus 15% vs M. fortuitum 4%

Attributed to M. fortuitum more commonly susceptible to multiple anti-mycobacterial agents

Clinical scenario fits with known epidemiology

But wait ……

No evidence of device colonization

Cases sporadic

Different manufacturers

Typing of five M. fortuitum isolates that

presented within a 9 month period excluded

clonality

No temporal association between access of port &

development of infection

LAP BANDING

Inflatable silicon band at

the gastric cardia

Adjusted by addition or

removal of aqueous solution

through a subcutaneous

port

More than 11, 000 procedures performed in

Australia during 2011.

INFECTIONS ASSOCIATED WITH LAP BANDS

HOW COMMON IS IT?

Complication N (Total = 8,504) Percent

Wound infection 24 0.28

Respiratory

complications

24 0.28

Infection of band or

reservoir

31 0.36

Subphrenic abscess 4 0.05

Infection (other inc.

sepsis)

16 0.19

Laparoscopic adjustable gastric banding in the

treatment of obesity: A systematic literature

review Chapman et al, Surgery, 2004

GRAFT SURVIVAL AND COMPLICATIONS AFTER LAPAROSCOPIC

GASTRIC BANDING FOR MORBID OBESITY--LESSONS LEARNED FROM

A 12-YEAR EXPERIENCE.

NAEF M ET AL, OBES SURG 2010

Prospective study of lap bands June 1998 – 2009

167 lap bands inserted

Follow up for 10 years post insertion

Early complication (<30 days) rate 7.8%

Late complications (>30 days) in 40.1%

3 band infections

40 esophageal dilatations

Concluded that lap banding should be performed

in selected cases only due to high complication,

re-operation and long term failure rates

MAJOR RESPIRATORY ADVERSE EVENTS AFTER LAPARASCOPIC

GASTRIC BANDING SURGERY FOR MORBID OBESITY

A. AVRIEL ET AL, RESPIRATORY MEDICINE 2012

Abundant published literature on short term complications but reports of long term complications, specifically respiratory symptoms remain scarce

Data from sole hospital in South Israel

30 patients hospitalized for major respiratory complications – annual incidence of 1.4%

Aspiration pneumonia: 19 (4 lung abscess, 3 empyema, 1 ARDS resulting in death)

Asthma: 1

Haemoptysis: 1

ILD: 5

Bronchiectasis: 3

Mean interval between insertion and onset of respiratory event : 51.5 months

MAJOR RESPIRATORY ADVERSE EVENTS AFTER LAPARASCOPIC

GASTRIC BANDING SURGERY FOR MORBID OBESITY

A. AVRIEL ET AL, RESPIRATORY MEDICINE 2012

In literature other studies showed much lower

frequencies of late respiratory complications

Most studies did not describe respiratory

complications

Only 6 other case reports described late

respiratory complications following lap banding

Surprising as high reported rates of recurrent

vomiting and esophageal dilatation

Suggests under-reporting

OUR PATIENT TO DATE….

Lap band culture: Candida parapsilosis

No Mycobacteria spp. isolated from lap band or port

culture

RHH RECORDS

4 patients with Mycobacteria spp. isolated from

lap bands in the past 5 years

3: M. fortuitum complex

1: M. avium complex

TREATMENT OF RGM

All resistant to first-line anti-tuberculous agents

Susceptibility patterns vary greatly between

species

No single antimicrobial agent (except amikacin)

is active against all species

In lap band infections, removal of device essential

RGM BACTERAEMIA TREATMENT

Quinolone Macrolide

M. abscessus Usually resistant Usually susceptible

M. chelonae Usually resistant Usually susceptible

M. fortuitum Usually susceptible Usually resistant

M. neoaurum Usually susceptible Usually resistant

M. mucogenicum Usually susceptible Usually susceptible

Initial empirical anti-mycobacterial

combination should ideally include amikacin, a

quinolone and a macrolide.

El Helou et al, Lancet Infect Dis 2013

El Helou et al, Lancet Infect Dis 2013

CAUTION

Possible intrinsic resistance to macrolides due to

inducible erythromycin methylase genes (erm

gene) Nash et al. J Antimicrob Chemother, 2005 February

Caution with macrolide use even though in vitro

sensitivity

ATS/IDSA STATEMENT: M. FORTUITUM

Lung disease: At least 2 agents with in vitro

activity, for at least 12 months of negative

sputum cultures

Serious skin, bone & soft tissue: At least 2 agents

with in vitro activity, minimum of 4 months

Bone infection: 6 months therapy recommended

OUR PATIENT’S ISOLATE’S SENSITIVITIES

Drug Sensitivity of our

patient

Expected

sensitivity

Amikacin S 100%

Cefoxitin R 19 – 50%

Ciprofloxacin S 62 – 100%

Clarithromycin R 55 – 65%

Cotrimoxazole S 49 – 88%

Doxycycline S 13 – 56%

Imipenem I 60 – 63%

Moxifloxacin S -

Linezolid I 68 – 100%

Currently on Ciprofloxacin + Cotrimoxazole + Doxycycline

TAKE HOME MESSAGES

Respiratory infections are not infrequent

complications of gastric lap band procedures

and are likely to be under-reported

RGM are important pathogens, particularly

M. fortuitum and M. abscessus, in the

following settings:

gastroesophageal disorders and chronic vomiting

gastric lap band device infections

REFERENCES

A spatial epidemiological analysis of nontuberculous mycobacterial infections in Queensland, Australia. Michael P Chou et al BMC Infectious Diseases 2014

Griffith et al, Clinical features of pulmonary disease caused by rapidly growing mycobacteria. Rev Respir Dis 1993

Rapidly Growing Mycobacteria associated with Laparoscopic Gastric Banding, Australia, 2005–2011. Hugh L. Wright et al. Emerging Infectious Diseases Vol. 20, No. 10, Oct 2014

Laparoscopic adjustable gastric banding in the treatment of obesity: A systematic literature review. Chapman et al, Surgery, 2004

Graft survival and complications after laparoscopic gastric banding for morbid obesity--lessons learned from a 12-year experience. Naef M et al, Obes Surg 2010

Major respiratory adverse events after laparascopic gastric banding surgery for morbid obesity. A. Avriel et al, Respiratory Medicine 2012

Rapidly growing mycobacterial bloodstream infections. El Helou et al. Lancet Infect Diseases 2013

An Official ATS/IDSA Statement : Diagnosis, treatment and prevention of Nontuberculous Mycobacterial Diseases. American Thoracic Society Documents. 2007

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