Multidrug resistant Proteus mirabilis and Escherichia coli causing fulminant necrotising fasciitis: a case report
Yeika et al. BMC Res Notes
Multidrug resistant Proteus mirabilis and Escherichia coli causing fulminant necrotising fasciitis: a case report
Eugene Vernyuy Yeika 0 1 2
Joyce Bei Foryoung 0 1
Derrick Tembi Efie 1
Eugene Adze Nkwetateba 1
Paul Nkemtendong Tolefac 1
Marcelin Ngowe Ngowe 3
0 Saint Elizabeth Catholic General Hospital and Cardiac Centre Shisong , PO Box 8, Kumbo , Cameroon
1 Health and Human Development Research Group , Douala , Cameroon
2 Clinical Research Education Networking and Consultancy , Douala , Cameroon
3 Faculty of Health Sciences, University of Buea , Buea , Cameroon
Background: Necrotizing fasciitis is a rare soft tissue infection characterized by rapid progressive necrosis with relative sparing of underlying muscles. This case is reported to highlight the emergence of multidrug resistant microbes in recent days which limits the use of empiric antibiotic therapy and necessitates early cultures and sensitivity enabling targeted antibiotic therapy. Factors that lead to antimicrobial resistance especially in sub-Saharan Africa have also been discussed. Case presentation: We report the case of a 52-year-old black man who was referred to our centre for the management of cellulitis and suppurating ulcers of the right leg which had progressed to a wet gangrene. Following physical examination and work-up, a diagnosis of fulminant necrotizing fasciitis of the right leg caused by multidrug resistant Proteus mirabilis and Escherichia coli was made. Despite the broad-spectrum empiric antibiotic therapy and aggressive multiple surgical debridement, necrosis progressed leading to an above-knee amputation. Conclusion: Necrotizing fasciitis is a surgical emergency that requires prompt diagnosis and aggressive surgical debridement in order to reduce morbidity and mortality. The emergence of multidrug resistant organisms in recent days have limited the use of empiric antibiotic therapy, necessitating early culture and sensitivity and the use of susceptibility-guided antibiotic therapy. Timely action to control the use of antibiotics in sub-Saharan Africa will reduce multidrug resistance and delay the arrival of post-antibiotics era.
Necrotizing fasciitis; Multidrug resistance; Empiric antibiotics; Case report
Necrotizing fasciitis (NF) is a rare soft tissue infection
characterized by rapid progressive necrosis with relative
sparing of underlying muscles [
]. Patients with NF
usually present with nonspecific features like fever,
excruciating pain, oedematous and erythematous skin lesions
that often rapidly deteriorate to haemorrhagic blebs or
fluid-filled bullae and gangrenous necrosis [
70% of cases of NF are caused by polymicrobial
organisms with most cultures yielding a mixture of aerobic and
anaerobic organisms [
]. The most common
pathogens isolated from cultures are gram positive organisms
like β-hemolytic group A streptococcus, Staphylococcus
aureus, bacillus species, enterococci species and gram
negative organisms such as Klebsiella pneumonia,
Pseudomonas aeroginosa, Serratia species, Escherichia coli,
Clostridium species, Fusobacterium species, and
Prevotella species [
2, 7, 8
]. NF carries a high morbidity and
mortality especially when diagnosed late [
necessitating prompt diagnosis and timely treatment with radical
surgical debridement and empiric broad spectrum
antibiotic therapy [
]. The mortality rate due to NF ranges
from 25 to 35% despite empiric broad-spectrum
antibiotic therapy and surgical debridement [
]. This case is
reported to highlight that the emergence of multidrug
resistant organisms (MDRO) limits the use of empiric
antibiotic therapy and necessitates early cultures and
sensitivity to enable targeted antibiotic therapy. The
factors that lead to antimicrobial resistance especially in
sub-Saharan Africa (SSA) had also been discussed. MDR
is defined as non-susceptibility to at least one agent in
three or more antimicrobial categories [
A 52-year-old black man with no relevant past medical
history was referred to our centre for the management
of cellulitis. He presented with a swollen
erythematous and painful right leg that progressed to formation
of blebs, suppurating ulcers and a wet gangrene. This
started at knee joint 8 days prior to presentation and was
initially managed with over-the-counter amoxicillin and
diclofenac. The swelling later progressed to involve the
right leg with development of blister-like lesions 4 days
following the onset of symptoms. The patient also
developed generalised pruritic rash prompting consultation
at the regional hospital and there, a diagnosis of a
sepsis secondary to a cellulitis was made. Initial work-up
at the regional hospital comprised of a complete blood
count which revealed leucocytosis (white cell count of
53.9 × 109/l) with neutrophil predominance, normocytic
normochromic anaemia (haemoglobin of 3.9 g/dl) and
thrombocytosis (platelet count of 880 × 109/l). The blood
urea nitrogen was 114 mg/dl and serum creatinine was
2.1 mg/dl (l84.8 µmol/l). The patient was initially
managed with intravenous ceftriaxone 1 g 12 hourly,
intravenous metronidazole 500 mg 8 hourly and subcutaneous
enoxaparin 4000 IU 24 hourly and was also transfused
two units of compatible whole blood. The patients’ stay at
the regional hospital was marked by persistence of fever,
progressive ulceration of the leg, bullae formation and
the onset of gangrene prompting referral to Saint
Elizabeth Catholic General Hospital Shisong following 4 days
Physical examination upon arrival at our centre
revealed a temperature of 38.9 °c, respiratory rate of
23 breaths/min, blood pressure of 99/70 mmHg and a
pulse rate of 114 beats/min. The patient was alert with
pale conjunctivae and anicteric sclerae and his weight
was 66 kg. His left leg was swollen, warm, fluctuant with
ulcerated skin and necrosis to the level of the knee joint
(Fig. 1). All digits of the right foot were pale and cold with
absent posterior tibial pulse. The following investigations
were conducted: a random blood glucose was 150 mg/dl
(8.3 mmol/l) and a fasting blood glucose done 16 h later
was 117 mg/dl (6.5 mmol/l). A complete blood count
revealed a white cell count of 16.4 × 109/l with
neutrophil predominance, a microcytic hypochromic anaemia
with haemoglobin level of 7.2 g/dl and platelet count of
569 × 109/l. A diagnosis of fulminant necrotizing fasciitis
The following parenteral antibiotics were given upon
admission: ampicillin 1 g 6 hourly, gentamycin 80 mg
12 hourly and metronidazole 500 mg 8 hourly; analgesia
included intravenous paracetamol 1 g 6 hourly and
fluids. After counselling and consent, surgical debridement
was done under general anesthesia 12 h following
hospitalization. Visualization during surgical exploration
confirmed the diagnosis of NF (Figs. 2 and 3). Debridement
was repeated on day 3 and day 7 of hospitalization. After
debridement, the wound was washed and dressed 12
hourly with Dakin’s solution and normal saline. A wound
swab was sent for culture and sensitivity and Proteus
mirabilis and E. coli were isolated. Necrosis progressed
despite multiple and aggressive surgical debridement
resulting to an above-knee amputation. Two units of
compatible whole blood were transfused during surgery.
The patient continued having swinging pyrexia (Fig. 4)
and on post-operative day 6, the stump started
producing purulent discharges (Fig. 5). The second wound swab
was collected and sent for culture and sensitivity and it
still revealed P. mirabilis and E. coli were isolated. Proteus
mirabilis was sensitive only to the carbapenems
(imipenem and meropenem) while E. coli was additionally
sensitive to ofloxacin and ornidazole (Table 1).
Further management involved removal of sutures,
debridement of necrosed tissue and initiation of
parenteral meropenem 1 g given 8 hourly. Clinical progress was
marked by formation of granulation tissue. The wound
was closed up 6 days later and the patient was eventually
discharged after 7 weeks of hospitalization.
Discussion and conclusion
Multidrug resistance have been frequently reported in
recent days and threatens the effectiveness of successful
treatment of infections especially using empiric
antibiotics. The incidence of MDR microbes is on the rise over
the past decades, meanwhile many studies still advocate
for early broad-spectrum empiric or combination
antibiotic therapy [
]. Godebo et al. in a study to determine
multidrug resistance rate of bacterial isolates that caused
wound infections in a specialised centre in SSA, showed
that overall MDR among gram positive and gram
negative bacterial isolates were 77 and 59.3% respectively
]. The selection of appropriate antimicrobial agents
R resistant, S sensitive
for any suspected NF must take into account the nature
of patient’s exposure and local epidemiologic data [
Empiric antibiotic therapy is limited because it cannot
be used in the context of MDRO. This is the situation in
this case report as culture and sensitivity results revealed
resistance to all the antibiotics previously used. Some
pathogens also possess the ability to develop new or
ongoing resistance during treatment [
complicating the blind use of antibiotics. Progressive necrosis of
soft tissues despite the empiric use of antibiotic therapy
is a big indicator of MDR and warrants early culture and
sensitivity to enable the use of susceptibility-guided
antibiotic therapy. Routine and early culture and sensitivity
is a means for early detection of MDRO and early use of
susceptibility-guided antibiotic therapy should be done at
the level of referring hospitals. This does not only reduce
morbidity and mortality, but also reduces the length of
hospital stay and the cost of hospitalisation.
The key to successful management of patients with
necrotizing soft tissue infections relies on early
recognition, prompt and aggressive surgical debridement with
targeted antibiotic therapy [
3, 10, 14
]. Early diagnosis of
NF remains a challenge partly due to nonspecific skin
findings causing it to be misdiagnosed as cellulitis [
]. This patient was initially managed as cellulitis prior
to referral, and this delayed the diagnosis of NF. Such
delays in recognition and treatment will result in greater
soft tissue lost and increased risk of morbidity and
]. Early clinical differentiation between NF
and cellulitis is important for early surgical management.
Kobayashi et al. showed that delays in surgical treatment
of > 12 h are associated with an increased number of
surgical debridement, higher incidence of septic shock and
acute kidney injuries in patients with necrotizing soft
tissue infections . Unusual location of soft tissue
infections, lack of associated co-morbidities and/or risks
factors, absence of any history of preceding trauma or an
obvious breech in the continuity of skin or mucosa, or a
low Laboratory Risk Indicator for Necrotizing Fasciitis
(LRINEC) score thus excludes the diagnosis of NF [
Our patient presented no specific risk factors for NF and
no history of initiating trauma or breech in skin
continuity but however developed a life threating NF.
Although NF is associated with a high morbidity and
mortality, early diagnosis and surgical debridement have
shown a favourable outcome making it not just a medical
but also a surgical emergency [
]. The decision for
surgical debridement often comes late due to late
diagnosis. The LRINEC scoring system is used to assist in early
diagnosis of NF [
]. This is the only validated diagnostic
tool for NF currently in use and carries a positive
predictive value of 92% [
]. This tool is based on six
parameters at the time of presentation; C-reactive protein, total
white cell count, haemoglobin, serum sodium,
creatinine and glucose. A LRINEC score of 6 or more confers
a higher risk of NF [
]. The LRINEC scoring system has
not yet achieved wide-spread use due to some
investigations like C-reactive protein which requires over 24 h for
the results and is absent in most resource-limited
settings. The controversial views of some authors with many
papers questioning its usefulness in early recognition of
LRENIC in recognising NF have also limited it use [
Many studies have validated the ability of the LRINEC in
detecting NF and differentiating it from other soft tissue
infections like cellulitis that may clinically present in a
similar fashion while others haven’t [
]. The LRINEC
score is not adequately sensitive despite its high
specificity, and consequently a low LRINEC score cannot be
used to eliminate the diagnosis of NF [
to Patel and associates, the diagnosis of NF still heavily
relies on clinical findings such as pain, fever and
hemodynamic instability . In our patient, we gathered a
LRINEC score of 6 suggestive of NF despite the unavailability
of C-reactive protein, warranting a surgical exploration.
Modifying the LRINEC scoring system to include both
clinical and laboratory findings is therefore necessary to
improve the specificity and sensitivity of this scoring
system and make it more useful in resource limited settings.
Multidrug resistance has become a public health issue
with national and global dimensions. There are many
factors that contribute to the development of antibiotic
resistance including the absence of quality assurance
and antibiotic surveillance in most parts of SSA.
Treatment with sensitive antibiotics is not always evident in
resource-limited settings due to cost and unavailability of
most antibiotics. The existence of very few centres that
can conduct cultures and sensitivity in most countries in
SSA have prompted the inevitable use of empiric or
combined antibiotics. Due to the poor socioeconomic status
of patients, expensive antibiotics are avoided for empiric
treatment and can only be prescribed only following
antimicrobial culture and sensitivity, however very few
patients also afford for culture and sensitivity. Due to
lack of government policies restricting over-the-counter
sales of drugs especially antibiotics, many patients have
resorted to the use of self-prescribed antibiotics prior to
consultation which lead to usage of poor quality of drugs,
sub-therapeutic doses and non-respect of therapeutic
In recent years where MDR is frequently reported in
many parts of the world, we recommend the adoption
and use of Center for Infectious Disease Control
guidelines for management of MDRO. According to these
guidelines, the following strategies are inevitable means
to prevent, curb or reduce MDR: administrative
support in terms of government policies limiting the sales
of over-the-counter antibiotics, creation of antibiotics
surveillance departments in the public health
ministries and education of the masses on the judicious use of
antimicrobial agents. The diversity of potential pathogens
resistant to commonly prescribed antibiotics underscores
the importance of sustained and standardized
antimicrobial resistance surveillance and antibiotic stewardship
programmes in developing countries [
], yet these
programs are grossly absent in SSA.
LRINEC: Laboratory Risk Indicator for Necrotizing Fasciitis; MDR: multidrug
resistance; MDRO: multidrug resistant organisms; NF: necrotizing fasciitis; SSA:
EVY managed the patients and wrote the original manuscript. JBF, DTE, EAN,
PNT and MNN reviewed and corrected the manuscript. All authors read and
approved the final manuscript.
The authors wish to acknowledge the entire surgical team for the great work
they did in managing this patient.
The authors declare that they have no competing interests.
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